Drug Discovery Group

 

Ashoke Sharon

 


Name:            Sharon, Ashoke

 

e.mail:            asharon@rx.uga.edu

 

 

Education:

 

Degree

Year

Institution

Major

Ph. D

2001- 2004

Central Drug Research Institute, Lucknow, India

Medicinal and Structural Chemistry

M. Sc. Tech Pharmaceutical Chemistry

1995-1998

Deapartment of Chemistry, Lucknow University, Lucknow India

Pharmaceutical Chemistry

 

Experience:

 

Year

Position

Institution

Sept 2004 - Present

Postdoctoral Associate

College of Pharmacy, University of Georgia, USA.

August 2002- September 2004

Senior Research Fellow

Central Drug Research Institute, Lucknow India

April 2001- August 2002

Research Scholar

Central Drug Research Institute, Lucknow India

March 1999- April 2001

Research Associate

R & D (Organic Synthesis), Lupin Lab Ltd., Mandideep, M.P. India

 

Recent Accomplishment

Publication:       Journal of Medicinal Chemistry 2008:                                                    http://pubs.acs.org/cgi-bin/abstract.cgi/jmcmar/asap/abs/jm800201s.html

                        Journal of Fluorine Chemistry 2008:                                                                  http://dx.doi.org/10.1016/j.jfluchem.2008.06.007

Award: International Society of Antiviral Research 2007, Poster Award:                        http://isar.phrm.cf.ac.uk/node/30

 

Present Research

·                    Discovery of novel approach for Nucleoside Molecular Modeling (Conformational Search, Molecular Dynamic, Induced Fit Docking, In-silico ADMET prediction and Hit-Ranking) to target polymerase for HIV, HCV and HBV.

·                    IInd Generation: Design and Synthesis for Anti-HCV Compound.

·                    Discovery of Novel Nucleoside Prodrug Strategy for HIV, HCV and HBV.

           

           

Research Publications

 

1.                   One-pot synthesis of unsymmetical biaryls from suitably functionalized 2H-pyran-2-ones through carbanion induced ring-transformation reactions. V. J. Ram, P. Srivastava, N. Agarwal, Ashoke Sharon, P. R. Maulik J. Chem. Soc. Perkin Trans. 1 2001, 1953-1959.

2.                   A taxane diterpenoid from the needles of Taxus wallichianaS. K. Chattopadhyay, Ashoke Sharon, U. Yadav, S. Srivastava, V. K. Mehta, P. R. Maulik Acta. Cryst. 2001, E57, o11 o1158-o1160.

3.                   1,3-Bis(8-chlorotheophyllin-7-yl)propane: a molecule with no intramolecular stacking. P. R. Maulik, K. Avasthi, S. Sarkhel, Ashoke Sharon, D. S. Rawat, C. Bal Acta. Cryst. 2001, E57, o1163-o1165.

4.                   A taxane diterpenoid from the heartwood of Taxus wallichiana. S. K. Chattopadhyay, Ashoke Sharon, U. Yadav, S. Srivastava, V. K. Mehta, P. R. Maulik Acta. Cryst. 2002, E58, o154-o155.

5.                   An expeditious synthesis of imidazo[1,2-a]pyridines through nucleophile induced ring transformation reactions of 6-aryl-4-methylsulfanyl-2H-pyran-2-one-3-carbonitriles. V. J. Ram, N. Agarwal, Ashoke Sharon, P. R. Maulik Tetrahedron Lett. 2002, 43, 307-310.

6.                   Carbanion induced synthesis of annulated unsymmetrical biaryls through ring transformation of 2H-pyran-2-one. V. J. Ram, N. Agarwal, A. S. Saxena, Farhanullah, Ashoke Sharon, P. R. Maulik J. Chem. Soc. Perkin Trans. 1 2002, 1426-1437.

7.                   Isomeric pyrazolo[3,4-d]pyrimidine-based molecules: Disappearance of dimerization due to interchanged substitutions. K. Avasthi, D. S. Rawat, T. Chandra, Ashoke Sharon, P. R. Maulik Acta Cryst. 2002, C58, o311-o313.

8.                   A stacked pyrazolo[3,4-d]pyrimidine-based flexible molecule: the effect of a bulky benzyl group on intermolecular stacking in comparison with methyl and ethyl groups. K. Avasthi, A. Tewari, D. S. Rawat, Ashoke Sharon, P. R. Maulik Acta. Cryst. 2002, C58, o494-o495.

9.                   1,4-Dichloro-1,4-diphenyl-2,3-diazabuta-1,3-diene. V. K. Tandon, Ashoke Sharon, R. Bandichhor, P. R. Maulik  Acta. Cryst. 2002, E58, o869-870.

10.                Disappearance of inter- and intramolecular stacking due to one-atom addition in ‘propylene linker’ in pyrazolo [3,4-d]pyrimidine-based flexible molecule. K. Avasthi, S. M. Farooq, Ashoke Sharon, P. R. Maulik Acta. Cryst. 2002, E58, o940-o941.

11.                Unusual molecular conformation in dissymmetric propylene-linker compounds containing pyrazolo-[3,4-d]pyrimidinyl and phthalimido moieties. K. Avasthi, D. Bhagat, C. Bal, Ashoke Sharon, U. Yadav, Prakas R. Maulik Acta Cryst. 2003, C59, o1-o4.

12.                Intermolecular stacking in pyrazolo[3,4-d]pyrimidine-based pentamethylene-linked flexible molecules. K. Avasthi, S. M. Farooq, A. K. Tewari, Ashoke Sharon, P. R. Maulik Acta. Cryst. 2003, C59, o42-o45.

13.                4,6-Bis-(methylsulfanyl)-1-(4-phenoxybutyl)-1H-pyrazolo[3,4-d]pyrimidine K. Avasthi, C. Bal, Ashoke Sharon, P. R. Maulik Acta. Cryst. 2003, C59, o-494-o495.

14.                2-(4-Chlorophenyl)-3-cyclohexylthiazolidin-4-one. Ashoke Sharon, T. Srivastava, S. B. Katti and P. R. Maulik Acta Cryst. 2003, E59, o1239-o1240.

15.                A stacked pyrazolo[3,4-d]pyrimidine based flexible molecule: the effect on stacking of an bulky iso-propyl group in comparison with methyl/ethyl group. K. Avasthi, S. M. Farooq, D. S. Rawat,  Ashoke Sharon, P. R. Maulik Acta Cryst., 2003, C59, o523-o524.

16.                Structure-Based Drug Design: Synthesis, Crystal Structure, Biological Evaluation and Docking Studies for Mono- and Bis-benzo[b]oxepines as non-steroidal estrogens. S. Sarkhel, Ashoke Sharon, V. Trivedi, P. R. Maulik, M. M. Singh, P. Venugopalan, S. Ray Bioorg. Med. Chem. 2003, 11, 5025-5033.

17.                Absolute Configuration and Anticancer Activity of Taxiresinol and related Lignans of Taxus wallichiana. S. K. Chattopadhyay, T. R. S. Kumar, P. R. Maulik, S. Srivastava, A. Garh, Ashoke Sharon, A. S. Negi, S. P. S. Khanuja Bioorg. Med. Chem. 2003, 11, 4945-4948.

18.                Synthesis of Biphenanthrenyls and Role of C-H…X Noncovalent Interactions in Conformational Control. Ashoke Sharon, P. R. Maulik, C. Vithana, Y. Ohashi, V. J. Ram Eur. J. Org. Chem. 2004, 886-893.   

19.                Antihyperglycemic activity of 2-methyl-3,4,5-triaryl-1H-pyrroles in SLM and STZ model. A. Goel, N. Agarwal, F. V. Singh, Ashoke Sharon, P. Tiwari, M. Dixit, R. Pratap, A. K. Srivastava, P. R. Maulik, V. J. Ram Bioorg. Med. Chem. Lett. 2004, 14 1089–1092.

20.                An efficient amberlist 15 catalyzed synthesis of indole-pyrazole based tripodal heterocycles. Farhanullah, Ashoke Sharon, P. R. Maulik and V. J. Ram Tetrahedron Lett. 2004, 45, 5099-5102.

21.          An innovative approach to the synthesis of annelated [a]diaza-anthracenones through tandem cyclization Ashoke Sharon, P. R. Maulik, R. Roy, V. J. Ram Tetrahedron Lett. 2004, 45, 5815-5818.

22.          A concise synthesis of highly functionalized a,b-unsaturated g-butyrolactones through ring contraction of 2H-pyran-2-ones. D. Sil, Ashoke Sharon, P. R. Maulik, V. J. Ram Tetrahedron Lett. 2004, 45, 6273-6276.

23.          Synthesis of benzocyclobutanes through ring transformation reactions of 2H-pyran-2-ones. D. Sil, Ashoke Sharon, R. Pratap, P. R. Maulik, V. J. Ram  Synlett. 2004, 12, 2163-2164.

24.          One-pot synthesis of cyclopentadienones through ring contraction of 2H-pyran-2-one. D. Sil, Ashoke Sharon, P. R. Maulik, V. J. Ram Tetrahedron Lett. 2004, 45, 6619-6621.

25.          An one pot synthesis of annelated [a]aza-thieno[3,2-g]naphthalenone through ring transformation followed by photocyclization. R. Pratap, Ashoke Sharon, P. R. Maulik, V. J. Ram Tetrahedron Lett. 2005, 46, 85-87.

26.                Biaryls and heterobiaryls as a-glucosidase and protein tyrosine phosphatase inhibitors. Ashoke Sharon, R. Pratap, B. Tripathim A. K. Srivastava, P. R. Maulik, V. J. Ram Bioorg. Med. Chem. Lett. 2005, 15 1341-1344.

27.                Synthesis and X-ray structural studies of pyrimidin-2,4-dione and 2-thioxo-1H-pyrimidin-4-one bearing chloroethyl moiety . F. V. Singh, R. Kumar, Ashoke Sharon, C. K. Broder, J. A. K. Howard, A. Goel, P. R. Maulik. Journal of Molecular Structure, 2005, 740, 101-105.

28.                Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization. Ashoke Sharon, R. Pratap, P. R. Maulik, V. J. Ram  Tetrahedron. 2005, 61, 3781–3787.

29.                Regioselective Syntheses of Functionalized 2-Aminopyridines and 2-Pyridinones through Nucleophile-Induced Ring Transformation Reactions. A. Goel, F. V. Singh, Ashoke Sharon, P. R. Maulik Synlett, 2005, 623-626

30.                6-Aryl-4-methylsulfanyl-2H-pyran-2-one-3-carbonitriles as PPAR-γ activators. Ashoke Sharon, R. Pratap, R. Vatsyayan, U. Roy, P. R. Maulik, A. Goel, V. J. Ram Bioorg. Med. Chem. Lett. 2005, 15, 3356-3360.

31.                Synthesis and in vivo antihyperglycemic activity of 5-(1H-pyrazol-3-yl) methyl-1H-tetrazoles. Sharon, Ashoke.; Pratap, R.; Tiwari, P.; Srivastava, A.; Maulik, P. R.; Ram, V. J., Bioorganic & Medicinal Chemistry Letters 2005, 15, (8), 2115-2117.

32.                Stereoselective alkenylation of a 1, 3-disubstituted pyrazol-5-one through ring transformation of 2H-pyran-2-ones. Sil, D.; Kumar, R.; Sharon, Ashoke.; Maulik, P. R.; Ram, V. J., Tetrahedron Letters 2005, 46, (22), 3807-3809.

33.                Dixit, M.; Sharon, Ashoke.; Maulik, P. R.; Goel, A., A Controlled Synthesis of Nature-Mimicking Benzofurans and their Corresponding Dimers [1]. Synlett 2006, 1497-1502.

34.                Singh, F. V.; Kumar, R.; Sharon, Ashoke; Broder, C. K.; Howard, J. A. K.; Goel, A.; Maulik, P. R., Synthesis and X-ray structural studies of pyrimidin-2, 4-dione and 2-thioxo-1H-pyrimidin-4-one bearing chloroethyl moiety. Journal of Molecular Structure 2006, 782.

35.                Liu, P.; Sharon, Ashoke; Chu, C. K., Enantiomeric synthesis of carbocyclic d-4'-C-methylribonucleosides as potential antiviral agents. Tetrahedron: Asymmetry 2006, 17, (23), 3304-3314.

36.                Kim, Y. A.; Sharon, Ashoke; Chu, C. K.; Rais, R. H.; Al Safarjalani, O. N.; Naguib, F. N. M.; el Kouni, M. H., Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents. Biochemical Pharmacology 2007, 7.

37.                Narayanasamy, J.; Pullagurla, M. R.; Sharon, Ashoke; Wang, J.; Schinazi, R. F.; Chu, C. K., Synthesis and anti-HIV activity of (-)-ß-d-(2R, 4R)-1, 3-dioxolane-2, 6-diamino purine (DAPD)(amdoxovir) and (-)-ß-d-(2R, 4R)-1, 3-dioxolane guanosine (DXG) prodrugs. Antiviral Research 2007, 75, (3), 198-209.

38.                Kim, Y. A.; Sharon, Ashoke; Chu, C. K.; Rais, R. H.; Al Safarjalani, O. N.; Naguib, F. N. M.; el Kouni, M. H., Structure-Activity Relationships of 7-Deaza-6-benzylthioinosine Analogues as Ligands of Toxoplasma gondii Adenosine Kinase. J. Med. Chem. 2008.

39.                Peng, L.; Sharon, Ashoke; Chu, C. K., Fluorinated Nucleosides: Synthesis and Biological Implication. Journal of Fluorine Chemistry 2008, In Press.

 

Conferences

 

1.        Participated in “National Symposium on Potential of Natural Products in Drug Research and Young Scientists Awareness Programme”, Department of Chemistry, Lucknow University, Lucknow, Nov. 16, 1998.

2.        Participated in “National Symposium on Chemical Science: Advancing Frontiers”, Central Drug Research Institute, Lucknow, June 3-4, 2001.

3.        Synthesis and Crystal Structures of 6-(4-Chlorophenyl)-3-cyano-4-[N’-bis(4- fluorophenylmethyl)piperazino]2H-pyran-2-one and 4-(4-Chlorophenyl)-2-cyclopropyl-6-[N’-(2-pyridyl)piperazin-1-yl]benzonitrile. Ashoke Sharon, Vishnu J. Ram, Pratibha Srivastava, Nidhi Agarwal and Prakas R. Maulik  At fourth meeting of the Asian Crystallographic Association (AsCA’01), IISc Bangalore, Nov 18-21, 2001.

4.         Rotameric restriction in biaryl system due to presence of  C-H…O and C-H…N  non-covalent interaction. Ashoke Sharon, Prakas R. Maulik and Vishnu Ji Ram Interanational Symposium on Drug Discovery and Process Research, Shivaji University, Kolhapur, India, Jan 23-25, 2003.

5.         Molecular modeling studies of acetophenone derivative for obtaining suitable ligands as PTP1B inhibitors. Ashoke Sharon, Manish Dixit, Prakas R. Maulik and Atul Goel International Symposium on Current Trends in Drug Discovery Research, CDRI, Lucknow, India, Feb 17-20, 2004.

6.        Participated in conference “Bridging the Sciences: HIV Vaccine Research and Drug Development” at Emory University Conference Center Hotel, Atlanta, USA. May 19-20, 2005.

7.        Synthesis and Anti-HIV Activity of DAPD (Amdoxovir) Prodrugs In Vitro Against M184V HIV Mutant. J. Narayanasamy,  Ashoke Sharon, M. R. Pullagurla, R. F. Schinazi, and C. K. Chu . 231st National ACS Meeting, Atlanta,USA. March 26- March 30, 2006.

 

 

 Research Skills  

                                                                                                                                           

1.               Organic Synthesis:

·          Well-versed with planning and handling, of small/large scale organic reactions including structural elucidation by spectroscopic techniques

·          Experience in polymorphic study of drug candidates and resolution of chiral molecules.

·          Presently, In-charge for Advance Purification Instrument (CombiFlash) for Flash Chromatography using normal and functionalized silica.

2.              Drug Design:  

·          In-silico approach for modeling and docking experiments to design and optimize the molecule to become lead or better active.

·          Well-versed with software such as Schrödinger Suite and Sybyl  (Tripos), on Silicon Graphics Workstation.

3.              Crystallography:

·         Familiar with single crystal preparation, mounting of crystal, handling of X-ray diffractometer (Bruker P4 System) with its related components, and data collection.

·          Well versed with crystallographic software such as XSCANS, SHELXTL, etc. to handle the X-ray data and structural interpretation.

 

Computer Skills        

v      Present responsibility includes as Administrator to maintain SGIs (Origin 300, 32 Processor System), SGI workstation and other several PCs and MAC for our group (20-Post-doc Group).

v      Familiar with handling, installation and troubleshooting for Advanced Molecular Modeling Software.

 

Professional Membership               

1.       Member of the Publication Committee of International Society of Antiviral Research.

2.       Member of American Chemical Society.

3.       Member of Indian Crystallographic Association

4.       Member of Indian Society of Chemist and Biologist.