Sunday 17 July 2016

Sreeni Labs Private Limited, Hyderabad, India ready to deliver New, Economical, Scalable Routes to your advanced intermediates & API's in early Clinical Drug Development Stages

str1

Sreeni Labs Private Limited, Hyderabad, India is ready to take up challenging synthesis projects from your preclinical and clinical development and supply from few grams to multi-kilo quantities. Sreeni Labs has proven route scouting ability  to  design and develop innovative, cost effective, scalable routes by using readily available and inexpensive starting materials. The selected route will be further developed into a robust process and demonstrate on kilo gram scale and produce 100's of kilos of in a relatively short time.
Accelerate your early development at competitive price by taking your route selection, process development and material supply challenges (gram scale to kilogram scale) to Sreeni Labs…………

INTRODUCTION

Sreeni Labs based in Hyderabad, India is working with various global customers and solving variety of challenging synthesis problems. Their customer base ranges from USA, Canada, India and Europe. Sreeni labs Managing Director, Dr. Sreenivasa Reddy Mundla has worked at Procter & Gamble Pharmaceuticals and Eli Lilly based in USA.
The main strength of Sreeni Labs is in the design, development of innovative and highly economical synthetic routes and development of a selected route into a robust process followed by production of quality product from 100 grams to 100s of kg scale. Sreeni Labs main motto is adding value in everything they do.
They have helped number of customers from virtual biotech, big pharma, specialty chemicals, catalog companies, and academic researchers and drug developers, solar energy researchers at universities and institutions by successfully developing highly economical and simple chemistry routes to number of products that were made either by very lengthy synthetic routes or  by using highly dangerous reagents and Suzuki coupling steps. They are able to supply materials from gram scale to multi kilo scale in a relatively short time by developing very short and efficient synthetic routes to a number of advanced intermediates, specialty chemicals, APIs and reference compounds. They also helped customers by drastically reducing number of steps, telescoping few steps into a single pot. For some projects, Sreeni Labs was able to develop simple chemistry and avoided use of palladium & expensive ligands. They always begin the project with end in the mind and design simple chemistry and also use readily available or easy to prepare starting materials in their design of synthetic routes
Over the years, Sreeni labs has successfully made a variety of products ranging from few mg to several kilogram scale. Sreeni labs has plenty of experience in making small select libraries of compounds, carbocyclic compounds like complex terpenoids, retinal derivatives, alkaloids, and heterocyclic compounds like multi substituted beta carbolines, pyridines, quinolines, quinolones, imidazoles, aminoimidazoles, quinoxalines, indoles, benzimidazoles, thiazoles, oxazoles, isoxazoles, carbazoles, benzothiazoles, azapines, benzazpines, natural and unnatural aminoacids, tetrapeptides, substituted oligomers of thiophenes and fused thiophenes, RAFT reagents, isocyanates, variety of ligands,  heteroaryl, biaryl, triaryl compounds, process impurities and metabolites.
Sreeni Labs is Looking for any potential opportunities where people need development of cost effective scalable routes followed by quick scale up to produce quality products in the pharmaceutical & specialty chemicals area. They can also take up custom synthesis and scale up of medchem analogues and building blocks.  They have flexible business model that will be in sink with customers. One can test their abilities & capabilities by giving couple of PO based (fee for service) projects.

Some of the compounds prepared by Sreeni labs;
str1str1
str1str1
str1str1
str1str1
str1str1
str1str1





See presentation below

LINK ON SLIDESHARE



Managing Director at Sreeni Labs Private Limited

Few Case Studies : Source SEEENI LABS

QUOTE.............
One virtual biotech company customer from USA, through a common friend approached Sreeni Labs and told that they are buying a tetrapeptide from Bachem on mg scale at a very high price and requested us to see if we can make 5g. We accepted the challenge and developed solution phase chemistry and delivered 6g and also the process procedures in 10 weeks time. The customer told that they are using same procedures with very minor modifications and produced the tetrapeptide ip to 100kg scale as the molecule is in Phase III.


One East coast customer in our first meeting told that they are working with 4 CROs of which two are in India and two are in China and politely asked why they should work with Sreeni Labs. We told that give us a project where your CROs failed to deliver and we will give a quote and work on it. You pay us only if we deliver and you satisfy with the data. They immediately gave us a project to make 1.5g and we delivered 2g product in 9 weeks. After receiving product and the data, the customer was extremely happy as their previous CRO couldn't deliver even a milligram in four months with 3 FTEs.


One Midwest biotech company was struggling to remove palladium from final API as they were doing a Suzuki coupling with a very expensive aryl pinacol borane and bromo pyridine derivative with an expensive ligand and relatively large amount of palldium acetate. The cost of final step catalyst, ligand and the palladium scavenging resin were making the project not viable even though the product is generating excellent data in the clinic. At this point we signed an FTE agreement with them and in four months time, we were able to design and develop a non suzuki route based on acid base chemistry and made 15g of API and compared the analytical data and purity with the Suzuki route API. This solved all three problems and the customer was very pleased with the outcome.


One big pharma customer from east coast, wrote a structure of chemical intermediate on a paper napkin in our first meeting and asked us to see if we can make it. We told that we can make it and in less than 3 weeks time we made a gram sample and shared the analytical data. The customer was very pleased and asked us to make 500g. We delivered in 4 weeks and in the next three months we supplied 25kg of the same product.


Through a common friend reference, a European customer from a an academic institute, sent us an email requesting us to quote for 20mg of a compound with compound number mentioned in J. med. chem. paper. It is a polycyclic compound with four contiguous stereogenic centers.  We gave a quote and delivered 35 mg of product with full analytical data which was more pure than the published in literature. Later on we made 8g and 6g of the same product.


One West coast customer approached us through a common friend's reference and told that they need to improve the chemistry of an advanced intermediate for their next campaign. At that time they are planning to make 15kg of that intermediate and purchased 50kg of starting raw material for $250,000. They also put five FTEs at a CRO  for 5 months to optimize the remaining 5 steps wherein they are using LAH, Sodium azide,  palladium catalyst and a column chromatography. We requested the customer not to purchase the 50kg raw material, and offered that we will make the 15kg for the price of raw material through a new route  in less than three months time. You pay us only after we deliver 15 kg material. The customer didn't want to take a chance with their timeline as they didn't work with us before but requested us to develop the chemistry. In 7 weeks time, we developed a very simple four step route for their advanced intermediate and made 50g. We used very inexpensive and readily available starting material. Our route gave three solid intermediates and completely eliminated chromatographic purifications.


One of my former colleague introduced an academic group in midwest and brought us a medchem project requiring synthesis of 65 challenging polyene compounds on 100mg scale. We designed synthetic routes and successfully prepared 60 compounds in a 15 month time.  
UNQUOTE............

The man behind Seeni labs is Dr. Sreenivasa Reddy Mundla 
Sreenivasa Reddy

Dr. Sreenivasa Reddy Mundla

Managing Director at Sreeni Labs Private Limited
Sreeni Labs Private Limited
Road No:12, Plot No:24,25,26
  • IDA, Nacharam
    Hyderabad, 500076
    Telangana State, India
Links
Dr. Sreenivasa Mundla Reddy
Dr. M. Sreenivasa Reddy obtained Ph.D from University of Hyderabad under the direction Prof Professor Goverdhan Mehta in 1992. From 1992-1994, he was a post doctoral fellow at University of Wisconsin in Professor Jame Cook's lab. From 1994 to 2000,  worked at Chemical process R&D at Procter & Gamble Pharmaceuticals (P&G). From 2001 to 2007 worked at Global Chemical Process R&D at Eli Lilly and Company in Indianapolis. 
In 2007  resigned to his  job and founded Sreeni Labs based in Hyderabad, Telangana, India  and started working with various global customers and solving various challenging synthesis problems. 
The main strength of Sreeni Labs is in the design, development of a novel chemical route and its development into a robust process followed by production of quality product from 100 grams to 100's of kg scale.
 
They have helped number of customers by successfully developing highly economical simple chemistry routes to number of products that were made by Suzuki coupling. they are able to shorten the route by drastically reducing number of steps, avoiding use of palladium & expensive ligands. they always use readily available or easy to prepare starting materials in their design of synthetic routes.
Sreeni Labs is Looking for any potential opportunities where people need development of cost effective scalable routes followed by quick scale up to produce quality products in the pharmaceutical & specialty chemicals area. They have flexible business model that will be in sink with customers. One can test their abilities & capabilities by giving PO based projects

Experience



Founder & Managing Director

Sreeni Labs Private Limited
August 2007 – Present (8 years 11 months)
Sreeni Labs Profile
Sreeni Labs Profile
View On SlideShare


Principal Research Scientist

Eli Lilly and Company
March 2001 – August 2007 (6 years 6 months)




Senior Research Scientist

Procter & Gamble
July 1994 – February 2001 (6 years 8 months)

Education


University of Hyderabad

Doctor of Philosophy (Ph.D.), 
1986 – 1992

PUBLICATIONS
Aug 2010 · ChemInform
Apr 2008 · Journal of Medicinal Chemistry
Feb 2008 · ChemInform
Nov 2007 · Tetrahedron
Apr 2006 · Journal of Medicinal Chemistry
Aug 2003 · Tetrahedron Letters
Nov 2000 · ChemInform
Read at
[LINK]


Patents by Inventor Dr. Sreenivasa Reddy Mundla
  • Patent number: 7872020
    Abstract: The present invention provides crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro -4H-pyrrolo[1,2-b]pyrazole monohydrate.
    Type: Grant
    Filed: June 29, 2006
    Date of Patent: January 18, 2011
    Assignee: Eli Lilly and Company
    Inventor: Sreenivasa Reddy Mundla
  • Publication number: 20100120854
    Abstract: The present invention provides crystalline 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate.
    Type: Application
    Filed: June 29, 2006
    Publication date: May 13, 2010
    Applicant: ELI LILLY AND COMPANY
    Inventor: Sreenivasa Reddy Mundla
  • Patent number: 6066740
    Abstract: The present invention provides a process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydroyrimidine derivatives by preparing the corresponding activated 2-thio-subsituted-2-derivative in a two-step, one-pot procedure and by further reacting yields this isolated derivative with the appropriate amine or its salts in the presence of a proton source. The present process allows for the preparation of 2-amino-2-imidazolines, quanidines, and 2-amino-3,4,5,6-tetrahydropyrimidines under reaction conditions that eliminate the need for lengthy, costly, or multiple low yielding steps, and highly toxic reactants. This process allows for improved yields and product purity and provides additional synthetic flexibility.
    Type: Grant
    Filed: November 25, 1997
    Date of Patent: May 23, 2000
    Assignee: The Procter & Gamble Company
    Inventors: Michael Selden Godlewski, Sean Rees Klopfenstein, Sreenivasa Reddy Mundla, William Lee Seibel, Randy Stuart Muth
TGF-β inhibitors
US 7872020 B2
The present invention provides 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl) -5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole monohydrate, i.e., Formula I.
Figure US07872020-20110118-C00002
EXAMPLE 1 Preparation of 2-(6-methyl-pyridin-2-yl)-3-[6-amido-quinolin-4-yl-5,6-dihydro-4H -pyrrolo[1,2-b]pyrazole monohydrate
Figure US07872020-20110118-C00008
Galunisertib
1H NMR (CDCl3): δ=9.0 ppm (d, 4.4 Hz, 1H); 8.23-8.19 ppm (m, 2H); 8.315 ppm (dd, 1.9 Hz, 8.9 Hz, 1H); 7.455 ppm (d, 4.4 Hz, 1H); 7.364 ppm (t, 7.7 Hz, 1H); 7.086 ppm (d, 8.0 Hz, 1H); 6.969 ppm (d, 7.7 Hz, 1H); 6.022 ppm (m, 1H); 5.497 ppm (m, 1H); 4.419 ppm (t, 7.3 Hz, 2H); 2.999 ppm (m, 2H); 2.770 ppm (p, 7.2 Hz, 7.4 Hz, 2H); 2.306 ppm (s, 3H); 1.817 ppm (m, 2H). MS ES+: 370.2; Exact: 369.16
ABOVE MOLECULE IS
Galunisertib
Phase III
LY-2157299
CAS No.700874-72-2


READ MY PRESENTATION ON
Accelerating Generic Approvals, see how you can accelerate your drug development programme

Accelerating Generic Approvals by Dr Anthony Crasto





KEYWORDS   Sreenivasa Mundla Reddy, Managing Director, Sreeni Labs Private Limited, Hyderabad, Telangana, India,  new, economical, scalable routes, early clinical drug development stages, Custom synthesis, custom manufacturing, drug discovery, PHASE 1, PHASE 2, PHASE 3,  API, drugs, medicines

Monday 20 June 2016

UCT Drug Discovery and Development Centre, H3D, pioneers world-class drug discovery in Africa.

H3D

UCT’s H3D is a center of excellence for research and innovation with an already strong track record in malaria drug  discovery. The vision of H3D is to be the leading organization for integrated drug discovery and development on the African continent.

ABOUT H3D

H3D is Africa’s first integrated drug discovery and development centre. The Centre was founded at the University of Cape Town in April 2011 and pioneers world-class drug discovery in Africa.

Our Vision

To be the leading organisation for integrated drug discovery and development from Africa, addressing global unmet medical needs.

Our Mission

To discover and develop innovative medicines for unmet medical needs on the African continent and beyond, by performing state-of-the-art research and development and bridging the gap between basic science and clinical studies.
We embrace partnerships with local and international governments, pharmaceutical companies, academia, and the private sector, as well as not-for-profit and philanthropic organisations, while  training scientists to be world experts in the field.
The H3D collaboration with the Medicines for Malaria Venture (MMV) focuses on delivering potential agents against malaria that will be affordable and safe to use. In line with the global aim to eradicate malaria, projects are pursued that not only eliminates blood-stage Plasmodium falciparum and Plasmodium vivax infection, but also acts against liver stages and blocks transmission of the infection. The projects embrace multidisciplinary activities to optimise hit compounds from screening libraries through the drug discovery pipeline and deliver clinical candidates.
Merck Serono Announces Recipients of the Second Annual €1 Million Grant for Multiple Sclerosis Innovation
Darmstadt, Germany, September 12, 2014 – Merck Serono, the biopharmaceutical division of Merck, today announced the recipients of the second annual Grant for Multiple Sclerosis Innovation (GMSI) at MS Boston 2014, the joint meeting of the Americas Committee for Treatment and Research in MS (ACTRIMS) and European Committee for Treatment and Research in MS (ECTRIMS), taking place September 10-13 in Boston, U.S.A.
Merck signed a research agreement with the University of Cape Town (UCT), South Africa, to co-develop a new R&D platform. It aims at identifying new lead programs for potential treatments against malaria, with the potential to expand it to other tropical diseases. It combines Merck’s R&D expertise and the drug discovery capabilities of the UCT Drug Discovery and Development Centre, H3D.
UCT’s H3D is a center of excellence for research and innovation with an already strong track record in malaria drug  discovery. The vision of H3D is to be the leading organization for integrated drug discovery and development on the African continent. They say that working with partners like Merck is critical to build up a comprehensive pipeline to tackle malaria and related infectious diseases.

Journal Publications:

  1. Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization C. Soares de Melo, T-S. Feng, R. van der Westhuyzen, R.K. Gessner, L. Street, G. Morgans, D. Warner, A. Moosa, K. Naran, N. Lawrence, H. Boshoff, C. Barry, C. Harris, R. Gordon, K. Chibale. Biorg. Med. Chem. 2015, 23, 7240-7250.
  2. A Novel Pyrazolopyridine with in Vivo Activity in Plasmodium berghei- and Plasmodium falciparum- Infected Mouse Models from Structure−Activity Relationship Studies around the Core of Recently Identified Antimalarial Imidazopyridazines. C. Le Manach, T. Paquet, C. Brunschwig, M. Njoroge, Z. Han, D. Gonzàlez Cabrera, S. Bashyam, R. Dhinakaran, D. Taylor, J. Reader, M. Botha, A. Churchyard, S. Lauterbach, T. Coetzer, L-M. Birkholtz, S. Meister, E. Winzeler, D. Waterson, M. Witty, S. Wittlin, M-B. Jiménez-Díaz, M. Santos Martínez, S. Ferrer, I. Angulo-Barturen, L. Street, and K. Chibale, J. Med. Chem. 2015, XX, XXXX
  3. Structure−Activity Relationship Studies of Orally Active Antimalarial 2,4-Diamino-thienopyrimidines. D. Gonzàlez Cabrera, F. Douelle, C. Le Manach, Z. Han, T. Paquet, D. Taylor, M. Njoroge, N. Lawrence, L. Wiesner, D. Waterson, M. Witty, S. Wittlin, L. Street and K. Chibale. J Med Chem. 2015, 58, 7572-7579.
  4. Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 2. Le Manach, T. Paquet, D. Gonzalez Cabrera, Y. Younis, D. Taylor, L. Wiesner, N. Lawrence, S. Schwager, D. Waterson, M.J. Witty, S. Wittlin, L. Street, and K. Chibale. J. Med. Chem. 2014, 57, 8839−8848.
  5. Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1. Le Manach, D. González Cabrera, F. Douelle, A.T. Nchinda, Y. Younis, D. Taylor, L. Wiesner, K. White, E. Ryan, C. March, S. Duffy, V. Avery, D. Waterson, M. J. Witty, S. Wittlin; S. Charman, L. Street, and K. Chibale. J. Med. Chem. 2014, 57, 2789-2798.
  6. 2,4-Diamino-thienopyrimidines as Orally Active Antimalarial Agents. D. González Cabrera, C. Le Manach, F. Douelle, Y. Younis, T.-S. Feng, T. Paquet, A.T. Nchinda, L.J. Street, D. Taylor, C. de Kock, L. Wiesner, S. Duffy, K.L. White, K.M. Zabiulla, Y. Sambandan, S. Bashyam, D. Waterson, M.J. Witty, A. Charman, V.M. Avery, S. Wittlin, and K. Chibale. J. Med. Chem. 2014,57, 1014-1022.
  7. Effects of a domain-selective ACE inhibitor in a mouse model of chronic angiotensin II-dependent hypertension. Burger, T.L. Reudelhuber, A. Mahajan, K. Chibale,E.D. Sturrock, R.M. Touyz. Clin. Sci. (Lond). 2014, 127(1), 57-63.
  8. Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor. Denti, S.K. Sharp, W.L. Kröger, S.L. Schwager, A. Mahajan, M. Njoroge, L. Gibhard, I. Smit, K. Chibale, L. Wiesner, E.D. Sturrock, N.H. Davies. Eur. J. Pharm. Sci.2014, 56, 113-119.
  9. Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors. R.G. Douglas, R.K. Sharma, G. Masuyer, L. Lubbe, I. Zamora, K.R. Acharya, K. Chibale, E.D. Sturrock. Sci. (Lond). 2014, 126(4),305-313.
  10. Fast in vitro methods to determine the speed of action and the stage-specificity of anti-malarials in Plasmodium falciparum. Le Manach, C. Scheurer, S. Sax, S. Schleiferböck, D. González Cabrera, Y. Younis, T. Paquet, L. Street, P.J. Smith, X. Ding, D. Waterson, M.J. Witty, D. Leroy, K. Chibale and S. Wittlin*. Malaria Journal, 2013, 12, 424.
  11. Structure-Activity-Relationship Studies Around the 2-Amino Group and Pyridine Core of Antimalarial 3,5-Diarylaminopyridines Lead to a Novel Series of Pyrazine Analogues with Oral in vivo Activity. Y. Younis, F. Douelle, González Cabrera, C. Le Manach, A.T. Nchinda, T. Paquet, L.J. Street, K.L. White, K. M. Zabiulla, J.T. Joseph,  S. Bashyam, D. Waterson, M.J. Witty, S. Wittlin, S.A. Charman, and K. Chibale*   J. Med. Chem. 2013, 56, 8860−8871.
  12. Cell-based Medicinal Chemistry Optimization of High Throughput Screening (HTS) Hits for Orally Active Antimalarials-Part 2: Hits from SoftFocus Kinase and other Libraries. Y. Younis, L. J. Street, D. Waterson, M.J. Witty, and K. Chibale. J. Med. Chem. 2013, 56, 7750−7754.
  13. Structure-Activity Relationship Studies of Orally active Antimalarial 3,5-Substituted 2-Aminopyridines. D. González Cabrera, F. Douelle, Y. Younis, T.-S. Feng, C. Le Manach, A.T. Nchinda, L.J. Street, C. Scheurer, J. Kamber, K. White, O. Montagnat, E. Ryan, K. Katneni, K.M. Zabiulla, J. Joseph, S. Bashyam, D. Waterson, M.J. Witty, S. Charman, S. Wittlin, and K. Chibale* J. Med. Chem. 2012, 55, 11022– 11030.
  14. 3,5-Diaryl-2-aminopyridines as a Novel Class of Orally Active Antimalarials Demonstrating Single Dose Cure in Mice and Clinical Candidate Potential. Y. Younis, F. Douelle, T.-S. Feng, D. González Cabrera, C. Le Manach, A.T. Nchinda, S. Duffy, K.L. White, M. Shackleford,  J. Morizzi, J. Mannila, K. Katneni, R. Bhamidipati, K. M. Zabiulla, J.T. Joseph,  S. Bashyam, D. Waterson, M.J. Witty, D. Hardick, S. Wittlin, V. Avery, S.A. Charman, and K. Chibale*.  J. Med. Chem.  2012, 55, 3479−3487.
  15. Novel Orally Active Antimalarial Thiazoles. D. González Cabrera, F. Douelle, T.-S Feng, A.T. Nchinda, Y. Younis, K.L. White, Wu,E. Ryan, J.N. Burrows,D. Waterson, M.J. Witty,S. Wittlin,S.A. Charman and K. Chibale.  J. Med. Chem. 2011, 54, 7713–7719.
  16. Synthesis and molecular modeling of a lisinopril-tryptophan analogue inhibitor of angiotensin I-converting enzyme. A.T. Nchinda, K. Chibale, P. Redelinghuys and E.D. Sturrock. Med. Chem. Lett. 2006, 16(17), 4616-4619.

Patents

  1. Anti-Malarial Agents. Y. Younis, K. Chibale, M.J. Witty, D. Waterson. (2016) US9266842 B2.
  2. New Anti-Malarial Agents. D. Waterson, M.J. Witty, K. Chibale, L. Street, D. González Cabrera, T. Paquet. EP patent application (2015), No. 15 176 514.6.
  3. Preparation of aminopyrazine compounds as antimalarial agents for treatment of malaria. Y. Younis, K. Chibale, M.J. Witty, D. Waterson. PCT Int Appl. (2013), WO 2013121387 A1 20130822.
  4. Preparation of peptides as angiotensin I-​converting enzyme (ACE) inhibitors. E.D. Sturrock, A.T. Nchinda, K. Chibale. PCT Int. ppl. (2006), WO 2006126087 A2 20061130.
  5. Preparation of peptides as angiotensin I-​converting enzyme (ACE) inhibitors, E.D. Sturrock, A.T. Nchinda, K. Chibale. PCT Int. ppl. (2006), WO 2006126086 A2 20061130.

Head Office, Medicinal Chemistry Unit

Physical Address:
Department of Chemistry
7.32 H3D Lab Suite, PD Hahn Building, Level 7
North Lane off Ring Road
Upper Campus, University of Cape Town
Rondebosch, 7700, South Africa

T | 021 650 5495
F | 021 650 5195

Postal Address:
University of Cape Town
Private Bag X3
Rondebosch 7701
South Africa
 
P. D. Hahn Bldg, Rondebosch, Cape Town,
Map of P. D. Hahn Bldg, Rondebosch, Cape Town, 7700, South Africa
 
P. D. Hahn Bldg, Rondebosch, Cape Town, 7700, South Africa
//////H3D, Africa,  integrated drug discovery and development centre,  University of Cape Town 

Metal Synergy in a Potential Anti-Cancer Drug

thumbnail image: Metal Synergy in a Potential Anti-Cancer Drug

Metal Synergy in a Potential Anti-Cancer Drug

Ruthenium teams up with platinum in a promising anticancer drug
/////////Ruthenium, anticancer drug, platinum

(±)-Integrifolin, Compound from plants keeps human cancer cells from multipying


STR1

CAS 89647-87-0
C15 H18 O4, 262.30
Azuleno[4,​5-​b]​furan-​2(3H)​-​one, decahydro-​4,​8-​dihydroxy-​3,​6,​9-​tris(methylene)​-​, (3aR,​4R,​6aR,​8S,​9aR,​9bR)​-
  • Azuleno[4,5-b]furan-2(3H)-one, decahydro-4,8-dihydroxy-3,6,9-tris(methylene)-, [3aR-(3aα,4β,6aα,8β,9aα,9bβ)]-
  • (3aR,4R,6aR,8S,9aR,9bR)-Decahydro-4,8-dihydroxy-3,6,9-tris(methylene)azuleno[4,5-b]furan-2(3H)-one
  • 8-epi-Deacylcynaropicrin
  • 8β-Hydroxyzaluzanin C
  • Integrifolin
  • Integrifolin (guaianolide)
Paper
thumbnail image: Total Synthesis of (±)-Integrifolin

(±)-Integrifolin

Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Total Synthesis of (±)-Integrifolin

Compound from plants keeps human cancer cells from multipying
Read more at Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

(±)-Integrifolin
Banksia integrifolia
Coast Banksia
Family: Proteaceae
Banksia integrifolia is a tall shrub or small tree 6 - 16m tall. It is common in sandy coastal areas, but also grows in the forests of tablelands. The light grey bark is hard and rough.
Mature leaves 5 -10 cm long, are stiff, entire (untoothed), dull dark green above and hairy-white underneath. They are generally lanceolate. Younger leaves are irregularly toothed and shorter than the mature leaves. The species name 'integrifolia' means whole-leaved.
The pale yellow flower spikes of Banksia integrifolia range from 7-14cm long and 7cm wide. The bent styles emerge from individual flowers on the spike, straightening and spreading.
A short time after flowering, the seed pods protrude cleanly from the woody cone and open to shed black, papery, winged seeds.
Banksia integrifolia flowers from January to June.
STR1
STR1
///////(±)-Integrifolin,  human cancer cells,  multipying
C=C1C(=O)O[C@@H]2[C@H]3C(=C)[C@@H](O)C[C@H]3C(=C)C[C@@H](O)[C@@H]12

Tuesday 7 June 2016

Predicting the Occurrence of Sticking during Tablet Production by Shear Testing of a Pharmaceutical Powder

A larger SI indicates a greater likelihood that sticking will occur.

Defining SI for Assessing Adhesion of Powder to the Punch

One cause of sticking is that when a powder is being compacted, the adhesive force between powder particles of the tablet and the punch surface exceeds the adhesive forces of powder particles within the tablet. Φp represents the frictional force acting between particles in the powder bed, and Φw represents the frictional force between the powder and the punch surface. The larger these values, the higher the friction and adhesion of the powder. We defined SI, which represents the degree of adhesion of a powder to the punch surface, as the value obtained by dividing Φw by Φp according to the following formula.
Sticking is a failure of pharmaceutical production that occurs when a powder containing a large amount of adhesive is being tableted. This is most frequently observed when long-term tableting is carried out, making it extremely difficult to predict its occurrence during the tablet formula design stage. The efficiency of the pharmaceutical production process could be improved if it were possible to predict whether a particular formulation was likely to stick during tableting. To address this issue, in the present study we prepared tablets composed of blended ibuprofen (Ibu), a highly adhesive drug, and measured the degree of adherence of powder particles to the surface of the tablet punch. We also measured the shear stress of the powder to determine the practical angle of internal friction (Φp) of the powder bed as well as the angle of wall friction (Φw) relative to the punch surface. These values were used to define a sticking index (SI), which showed a high correlation with the amount of Ibu that adhered to the punch during tableting; sticking occurred at SI >0.3. When the amount of lubricant added to the formulation was changed to yield tablets exhibiting different SI values without changing the compounding ratio, sticking did not occur at SI ≤0.3. These results suggest that determining the SI of a pharmaceutical powder before tableting allows prediction of the likelihood of sticking during tableting.

Predicting the Occurrence of Sticking during Tablet Production by Shear Testing of a Pharmaceutical Powder


///////////sticking, shear stress, internal friction angle, wall friction angle, sticking index, ibuprofen,  Tablet Production, Shear Testing, Pharmaceutical Powder

3,5-Dibromo-N-(4,6-difluorobenzo[d]thiazol-2-yl)thiophene-2-carboxamide having potent anti-norovirus activity

STR1

3,5-Dibromo-N-(4,6-difluorobenzo[d]thiazol-2-yl)thiophene-2-carboxamide

New and novel anti-norovirus agents
There is an urgent need for structurally novel anti-norovirus agents. In this study, we describe the synthesis, anti-norovirus activity, and structure–activity relationship (SAR) of a series of heterocyclic carboxamide derivatives. Heterocyclic carboxamide 1 (50% effective concentration (EC50)=37 µM) was identified by our screening campaign using the cytopathic effect reduction assay. Initial SAR studies suggested the importance of halogen substituents on the heterocyclic scaffold and identified 3,5-di-boromo-thiophene derivative 2j (EC50=24 µM) and 4,6-di-fluoro-benzothiazole derivative 3j (EC50=5.6 µM) as more potent inhibitors than 1. Moreover, their hybrid compound, 3,5-di-bromo-thiophen-4,6-di-fluoro-benzothiazole 4b, showed the most potent anti-norovirus activity with a EC50 value of 0.53 µM (70-fold more potent than 1). Further investigation suggested that 4b might inhibit intracellular viral replication or the late stage of viral infection.

3,5-Dibromo-N-(4,6-difluorobenzo[d]thiazol-2-yl)thiophene-2-carboxamide (4b)

STR1
According to the same procedure used for 2f, starting from 3,5-dibromothiophene-2-carboxylic acid (286 mg, 1.00 mmol) and 4,6-difluorobenzo[d]thiazol-2-amine (204 mg, 1.10 mmol), 4b (270 mg, 60%) was obtained as white powder. mp: 245–246°C. 1H-NMR (DMSO-d6) δ: 7.43 (1H, dt, J=10.2, 2.0 Hz), 7.56 (1H, s), 7.83 (1H, dd, J=8.4, 2.0 Hz). 13C-NMR (DMSO-d6) δ: 102.2 (dd, J=28.0, 23.1 Hz), 104.7 (dd, J=26.4, 3.3 Hz), 114.3, 118.4, 131.4 (d, J=7.4 Hz), 134.3 (d, J=10.7 Hz), 134.9, 135.2, 152.7 (d, J=241.2, 20.7 Hz), 158.3 (dd, J=242.2, 10.7 Hz), 159.0, 159.7. HPLC purity: >99%, ESI-MS m/z 453 [M+H]+.
Antiviral Activity and Cytotoxicity of Tetra-halogenated Hybrid Compounds
CompoundR6R7R8EC50 (µM)a)CC50 (µM)b)
4aClHH2.1>100
4bBrHBr0.53>100
4cClHCl1.1>100
4dClClH1.431
a) EC50 was evaluated by the CPE reduction assay. 280 TCID50/50 µL of MNV and a dilution series of each compound were incubated for 30 min. The mixture was exposed to RAW264.7 cells for 1 h (in duplicate). b) Cytotoxicity was evaluated by the WST-8 assay. RAW264.7 cells were treated with dilution series of each compound (in triplicate) for 72 h.

Discovery and Synthesis of Heterocyclic Carboxamide Derivatives as Potent Anti-norovirus Agents

How to Kill Norovirus


Norovirus is a contagious virus that affects many people each year. You can get norovirus through interaction with an infected person, by eating contaminated food, touching contaminated surfaces, or drinking contaminated water. However, there are ways to kill norovirus before it infects you. To do this, you will have to maintain personal hygiene and keep your home contamination-free.
Method1

Killing Norovirus with Good Hygiene

  1. Image titled Kill Norovirus Step 1
    1
    Wash your hands thoroughly. If you think you may have come into contact with the virus, you must wash your hands thoroughly to avoid the spread of infection. To wash your hands to avoid contamination, use soap and hot water. Alcohol hand sanitizer is generally considered ineffective against this particular kind of virus. You should wash your hands if[1]:
    • You have come into contact with someone who has norovirus.
    • Before and after you interact with someone with norovirus.
    • If you visit a hospital, even if you don’t think you interacted with anyone with norovirus.
    • After going to the bathroom.
    • Before and after eating.
    • If you are a nurse or doctor, wash your hands before and after coming into contact with an infected patient, even if you wear gloves.
  2. Image titled Kill Norovirus Step 2
    2
    Avoid cooking for others if you are sick. If you have been infected and are sick, do not handle any food or cook for others in your family. If you do, they are almost certain to get the infection too.
    • If a family member is contaminated, do not let them cook for anyone else. Try to limit the amount of time healthy family members spend with the sick family member.
  3. Image titled Kill Norovirus Step 3
    3
    Wash your food before eating or cooking it. Wash all food items such as meats, fruits and vegetables thoroughly before consumption or for use in cooking. This is important as norovirus has the tendency to survive even at temperatures well above 140 degrees Fahrenheit (60 degrees Celsius).[2]
    • Remember to carefully wash any vegetables or fruit, before consuming them, whether you prefer them fresh or cooked.
  4. Image titled Kill Norovirus Step 4
    4
    Cook your food thoroughly before eating it. Seafood should be cooked thoroughly before eating it. Quick steaming your food will generally not kill the virus, as it can survive the steaming process. Instead, bake or boil your food at temperatures higher than 140F (60C) if you are concerned about it’s origins.[3]
    • If you suspect any kind of food of being contaminated, you should dispose of it immediately. For instance, if a contaminated family member handled the food, you should either throw the food out or isolate it and make sure that only the person who already has the virus eats it.

Method2

Killing Norovirus in Your Home

  1. Image titled Kill Norovirus Step 5
    1
    Use bleach to clean surfaces. Chlorine bleach is an effective cleaning agent that kills norovirus. Increase the concentration or buy a new bottle of chlorine bleach if the bleach you have has been open for more than a month. Bleach becomes less effective the longer it remains open. Before applying bleach to a visible surface, test it somewhere that is not easily seen to make sure that it won’t damage the surface. If the surface is damaged by bleach, you can also use phenolic solutions, such as Pine-Sol, to clean the surface. There are certain concentrations of chlorine bleach you can use for different surfaces.[4]
    • For stainless steel surfaces and items used for food consumption: Dissolve one tablespoon of bleach in a gallon of water and clean the stainless steel.
    • For non-porous surfaces like countertops, sinks, or tile floors: Dissolve one third of a cup of bleach in a gallon of water.
    • For porous surfaces, like wooden floors: Dissolve one and two thirds of a cup of bleach in a gallon of water.
  2. Image titled Kill Norovirus Step 6
    2
    Rinse surfaces with clean water after using bleach. After cleaning the surfaces, leave the solution to work for 10 to 20 minutes. After the time period elapses, rinse the surface with clean water. After these two steps, close off the area, and leave it like that for one hour.
    • Leave the windows open, if possible, as breathing in bleach can be hazardous to your health.
  3. Image titled Kill Norovirus Step 7
    3
    Clean areas exposed to feces or vomit. For areas exposed to feces or vomit contamination there are special cleaning procedures that you should try to follow. This is because the vomit or feces of a person contaminated with norovirus can easily cause you to become infected. To clean the vomit or feces:
    • Put disposable gloves on. Consider wearing a facemask that covers your mouth and nose as well.
    • Using paper towels, gently clean the vomit and feces. Be careful not to splash or drip while cleaning.
    • Use disposable cloths to clean and disinfect the entire area with chlorine bleach.
    • Use sealed plastic bags to dispose of all the waste materials.
  4. Image titled Kill Norovirus Step 8
    4
    Clean your carpets. If the feces or vomit gets on a carpeted area, there are other steps you can take to make sure that the area is clean and disinfected. To clean the carpeted area:
    • Wear disposable gloves if you can while cleaning the carpets. You should also consider wearing a facemask that covers your mouth and nose.
    • Use any absorbent material to clean all the visible feces or vomit. Place all contaminated materials in a plastic bag to prevent aerosols from forming. The bag should be sealed and put into the garbage can.
    • The carpet should then be cleaned with steam at 170 degrees Fahrenheit (76 degrees Celsius) for about five minutes, or, if you want to save time, clean the carpet for one minute with 212 degrees Fahrenheit (100 degrees Celsius) steam.
  5. Image titled Kill Norovirus Step 9
    5
    Disinfect clothing. If any of your clothing or a family member’s clothing has become contaminated, or is suspected of having been contaminated, you should take care when washing the fabric. To clean clothing and linens:
    • Remove any traces of vomit or feces by wiping it away with paper towels or a disposable absorbent material.
    • Put the contaminated clothing into the washing machine in a pre-wash cycle. After this stage is complete, wash the clothes using a regular washing cycle and detergent. The clothes should be dried separately from the uncontaminated clothes. A drying temperature exceeding 170 degrees Fahrenheit is recommended.
    • Do not wash contaminated clothing with uncontaminated cleaning.

Method3

Treating Norovirus

  1. Image titled Kill Norovirus Step 10
    1
    Recognize symptoms. If you think you may have been infected with norovirus, it is helpful to know what symptoms to look for. If you do have the virus, the following steps will help you to deal with the illness while it lasts. Symptoms include[5]:
    • Fever. Just like in any other infection, the norovirus infection will cause fever. Fever is a way in which the body fights infection. The body temperature will rise, making the virus more vulnerable to the immune system. Your body temperature will most likely rise above 100.4 degrees Fahrenheit (38 degrees Celsius) when suffering from a Norovirus infection.
    • Headaches. High body temperatures will cause blood vessels to dilate in your entire body, including your head. The high amount of blood inside your head will cause pressure to build up, and the protective membranes covering your brain will suffer inflammation and become painful.
    • Stomach cramps. Norovirus infections usually settle in the stomach. Your stomach may become inflamed, causing pain.
    • Diarrhea. Diarrhea is a common symptom of Norovirus contamination. It occurs as a defense mechanism, through which the body is trying to flush out the virus.
    • Vomiting. Vomiting is another common symptom of an infection with Norovirus. Like in the case of diarrhea, the body is trying to eliminate the virus from the system by vomiting.
  2. Image titled Kill Norovirus Step 11
    2
    Understand that while there is no treatment, there are ways to manage symptoms. Unfortunately, there is no specific drug that acts against the virus. However, you can combat the symptoms that the norovirus causes. Remember that the virus is self-limiting, which means that it generally goes away on its own.
    • The virus generally lasts for a few days to a week.
  3. Image titled Kill Norovirus Step 12
    3
    Drink lots of fluids. Consuming a lot of water and other fluids will help to keep you hydrated. This can help to keep your fever low and your headaches to a minimum. It is also important to drink water if you have been vomiting or have had diarrhea. When these too symptoms occur, it is very likely that you will become dehydrated.
    • If you get bored with water, you can drink ginger tea, which may help to manage your stomach pains while also hydrating you.
  4. Image titled Kill Norovirus Step 13
    4
    Consider taking anti-vomiting drugs. Anti-emetic (vomit-preventing) drugs such as ondansetron and domperidone can be given to provide symptomatic relief if you are vomiting frequently.[6]
    • However, keep in mind that these drugs can only be obtained with a prescription from your doctor.
  5. Image titled Kill Norovirus Step 14
    5
    Seek medical help if the infection is severe. As mentioned above, most infections subside after a few days. If the virus persists for longer than a week, you should consider seeking medical help. This is particularly important if the person who is sick is a child or elderly person, or a person with lowered immunity