Motivated and enthusiastic researcher, looking for a position in Drug design and discovery approaches with regard to Synthetic and Natural Leads, where, I can perform with my effectiveness, efficiency, integrity and diligence towards research. Personal Biodata Date of Birth Nationality / Sex /Marital Status Current working details: Currently working as a Postdoctoral Fellow, under the supervision of Prof. Dr. Warinthorn Chavasiri, Department of Chemistry, and Dr. Siwaporn Boonyasuppayakorn, Assistant Professor, Division of Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Thailand. 15th Apr. 1986. Indian /Male / Married Postdoc Experience Sep. 2017 - : Postdoc Fellow (Carbohydrate Chemistry) Jul. 2018 Supervisor: Dr. JeyaKumar Kandasamay, Department of Chemistry, Indian Institute of Technology-(IIT-BHU), Varanasi, India. Indo-Max Plank Partner group Title "Photolabile protected Monosaccharides: Synthesis and application to oligosaccharide synthesis using as continuous flow photoreactor. Industrial experience Dr. Reddy's Institute of Life Sciences Worked as a Research Associate in Synthetic Research & Development, that leading to intellectual property generation, in Department of Center for Process Research & Innovation, at Dr. Reddy's Institute of Life Sciences, Hyderabad Central University Campus, Gachibowli, India (June. 2016-Aug. 2017) Dr. Vishnu Nayak B Brundavan Laboratory Pvt. Ltd. Worked as a Senior Chemist in Process Research & Development at Brundavan Laboratory Pvt. Ltd., Choutuppal, Hyderabad, Telangana, India (Apr. 2016-May. 2016). Academic background 2011-2016 : Ph. D. Pharmaceutical Chemistry (Medicinal Chemistry) Supervisor: Dr. B. N. Sinha, Professor & Co-supervisor Dr. Venkatesan Jayaprakash, Associate Professor, Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology (BIT)-Mesra, Ranchi, India. Thesis Title: "Design, Synthesis and Biological Screening of Monoamine oxidase inhibitors" (Registration Sept. 2011, Awarded May. 2017. 2010-2011 : Project Research assistant Project supervisor: Dr. T. Narender, Principal Scientist in Medicinal and Process Chemistry Division at CSIR-Central Drug Research Institute-Lucknow under master degree project. Period: 1 Year (June-2010 -June-2011). 2009-2011 : M.S. (Medicinal Chemistry): First division with CGPA 6.9 (64.60%) from National Institute of Pharmaceutical Education and Research (NIPER), Rae Bareli, Uttar Pradesh, India. 2005-2009 : B. Pharmacy (Pharmaceutical Sciences): First division with 67.68% from Osmania University, Hyderabad, Telangana, India 2002-2004 : Intermediate (Bi. P.C), First division (73.33%) from Board of Intermediate, Andhra Pradesh, India. 2001-2002 : 10 Class, First division with distinction (63.83%) from Board of Secondary Education, Andhra Pradesh, India. Competitive exams qualified CSIR-NET-June 2016, in Chemical Sciences, with 79 rank, conducted jointly by Council of Scientific and Industrial Research & University Grants Commission (CSIR-UGC), Govt. of India. GATE-2009, with 88.72 percentile, conducted by Indian Institute of Technology (IIT), Roorkee, Uttarkand. NIPER-JEE-2009. Conducted by NIPER-Mohali, India. GPAT-2015. Graduate Pharmacy Aptitude Test, Conducted by All India Council for Technical Education (AICTE), Govt. of India. Ph. D Entrance Exam-2011, conducted by Dept. of Pharmaceutical Chemistry, Birla Institute of Technology (BIT)-Mesra, Ranchi, India. EAMCET-2005, Conducted by Govt. of Andhra Pradesh, India th Dr. Vishnu Nayak B Awarded Scholarship/Fellowships * Recipient of the prestigious Birla Institute Fellowship Award 2011 - 14 for Pursuing Ph.D from Birla Institute of Technology (BIT)-Mesra, Ranchi, India. * Recipient of Fellowship from "Ministry of Chemicals & Fertilizers, Govt. of India (2009- 2011)" for pursuing M. S. (Pharm.) Chemistry from National Institute of Pharmaceutical Education and Research (NIPER)-Raebareli, Uttar Pradesh, India. * Recipient of Post Matric Fellowship from Govt. of Andhra Pradesh, 2005-2009 for pursuing B. Pharmacy from Osmania University Hyderabad, Andhra Pradesh, India. * Recipient of Fellowship from Govt. of Andhra Pradesh for pursuing Intermediate/10+2, 2002 - 2004 from, Board of Intermediate Education. Andhra Pradesh, India. International Research Publications 1. Sabina. Yasmin, Carmen. Cerchia, Fabio. Capone, Vishnu N. Badavath, et al., Discovery of Ferulic Acid Amides as a Novel Class of PPAR? Antagonists with Antidiabetic and Hypolipidemic Effect in Mice. Nature-Scientific Reports (Submitted manuscript ID: SREP-18-24666). 2. Chandrani Nath, Vishnu N. Badavath, Abhishek Thakur, Gulberk Ucar, Orlando Acevedo, Barij N. Sinha, Venkatesan Jayaprakash. Curcumin-based pyrazoline analogues as selective inhibitors of human monoamine oxidase A. Med. Chem. Commun., 2018, 9, 1164 - 1171 (IF: 2.608) 3. Varsha Tiwari, Vishnu Nayak Badavath, Adesh Kumar Singh, Jeyakumar Kandasamy. A highly efficient TEMPO-mediated oxidation of sugar primary alcohols into uronic acids using 1-chloro-1, 2-benziodoxol-3 (1H)-one at room temperature. Tetrahedron Letter, 2018, 59, (26), 2511-2514 (IF: 2.45). (ISSN-00404039). 4. Vishnu Nayak Badavath, Ipek Baysal, Gulberk Ucar, B. N. Sinha, Venkatesan Jayaprakash, Monoamine oxidase inhibitory activity of novel Pyrazoline analogues: Curcumin based design and synthesis, ACS-Medicinal Chemistry Letters. 2016, 7, 56-61. (IF: 3.79) (ISSN- 19485875) 5. B. Vishnu Nayak, S. Ciftci-Yabanoglu, S. S. Jadav, Monika Jagrat, B. N. Sinha, G. Ucar, Venkatesan Jayaprakash, Monoamine oxidase inhibitory activity of 3, 5-biaryl-4, 5dihydro-1H-pyrazole-1-carboxylate derivatives, European Journal of Medicinal Chemistry. 2013, 69, 762-767. (IF: 4.81) (ISSN-02235234). Dr. Vishnu Nayak B 6. Vishnu Nayak Badavath, S. C. Yabanoglu, S. Bhakat, A. K. Timiri, B.N. Sinha, G. Ucar, M. E.S. Soliman, V. Jayaprakash, Monoamine oxidase inhibitory activity of 2-aryl-4H- chromen-4ones, Bioorganic Chemistry. 2015, 58, 72 - 80 (IF: 3.92) (ISSN-10902120) 7. T. Narender, K. Venkateswarlu, B. Vishnu Nayak and S. Sarkar. A new chemical access for 3'- acetyl-4'-hydroxychalcones using BF3-Et2O via a regioselective Claisen-Schmidt condensation and its application in the synthesis of chalcone hybrids, Tetrahedron Letters. 2011, 52, 5794 - 5798. (IF: 2.45). (ISSN-00404039). 8. Vishnu Nayak Badavath, Ipek Baysal, Gulberk Ucar, S. K. Mondal, B. N. Sinha, V. Jayaprakash, MAO inhibitory activity of Ferulic Acid Amides: Curcumin based design and synthesis, Wiley-Archiv der Pharmazie, 2015, 348, 1-11. (IF: 2.28) (ISSN15214184). 9. S. S. Jadav, S. Kaptein, A. K. Timiri, Tine De B, Vishnu Nayak Badavath, Ramesh G, B. N. Sinha, Johan Neyts, Pieter Leyssen and Venkatesan J. Design, synthesis, optimization and antiviral activity of a class of hybrid dengue virus E protein inhibitors. Bioorganic & Medicinal Chemistry Letters. 2015, 25, 1747 - 1752 (IF: 2.48) (ISSN-0960894) 10. Vishnu Nayak Badavath, Chandrani Nath, Narayana M. Ganta, GulberkUcar, Barij N. Sinha, Venkatesan Jayaprakash. Design, synthesis, molecular docking and MAO inhibitory activity of 2-(arylmethylidene)-2,3-dihydro-1-benzofuran-3-one derivatives. ElsevierChinese Chemical Letters. 2017, 28 (7), 1528 - 1532 (IF: 2.63) (ISSN- 10018417) 11. Vishnu Nayak Badavath, G. Ucar, B. N. Sinha, S. K. Mondal, V. Jayaprakash. Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis-II. Wiley-Chemistry Select, 2016, 1, 1-7. (IF: 1.50) (ISSN- 2365 - 6549 12. Vishnu Nayak Badavath, S. S. Jadav, Boris Pastorino, Xavier de Lamballerie, B. N. Sinha, Venkatesan Jayaprakash. Synthesis and antiviral activity of 2-Phenyl-4H-chromen-4-one derivatives against Chikungunya virus. Letters in Drug Design and Discovery 2016, 13, 16. (IF: 2.25) (ISSN-15701808). 13. Vishnu Nayak Badavath, B. N. Sinha, Venkatesan Jayaprakash, Design, in-silico docking and predictive ADME properties of novel Pyrazoline derivatives with selective human MAO inhibitory activity, International Journal of Pharmacy and Pharmaceutical Sciences. 2015, 7, 277-282. (IF: 0.49) (ISSN-09751491). 14. Vishnu Nayak Badavath, A. K. Singh, S. S Jadav, N. Mishra, D. Abhimanyu, B. N. Sinha, Venkatesan J. Pyrazoline carboxylates as selective MAO-B inhibitors: Synthesis and Biological screening. Journal of Pharmaceutical Chemistry. 2015, 2, 1-5. (ISSN-23495731). 15. Vishnu Nayak Badavath, I. Baysal, G. Ucar, B. N. Sinha, S. K. Mondal, Venkatesan Dr. Vishnu Nayak B Jayaprakash. Monoamine oxidase-A inhibitory activity of novel Curcumin analogues. Journal of Pharmaceutical Chemistry 2015, 2, 12-17. (ISSN-2349-5731) 16. Vishnu Nayak Badavath, Alok Kumar, S. S. Jadav, B. N. Sinha, A. K. Pattnaik, Venkatesan J. Synthesis and Antidepressant activity of pyrazoline based MAO inhibitors. Journal of Pharmaceutical Chemistry 2016, 3, 1-3. (ISSN-2349-5731). 17. A. K. Timiri, Vishnu Nayak Badavath, B. N. Sinha, Venkatesan J, Subasri Selvarasu, Vishwanathan Vijayan, Velmurugan Devadasan. Synthesis, spectral and crystal studies of 2-(4, 6-diamino pyrimidin-2-ylthio)-N-m/p-tolyl/3, 4-dimethylacetamides. Formulation Development and Analysis. 2015, 1, 7-14. 18. Saravanabhavan, V murugesan, Vishnu Nayak Badavath, Venkatesan Jayaprakash. Molecular Docking and Biological Studies of Pyrido[2,3-a ]Carbazole derivatives. RSCOrganic Chemistry Frontiers. (Communicated) 19. Ravi Jarapula, Vishnu N. Badavath, Shriram Rekulapally, Sarangapani M, Development of New Bis-2-Oxoindoline Succinohydrazides as Anticancer agents- Biological Evaluation, 3DQSAR, Molecular Docking and ADMET Studies. Anti-Cancer Agents in Medicinal Chemistry (Manuscript Id: BMS-ACAMC-2018-154). 20. S. S. Jadav, Vishnu Nayak Badavath, Ramesh Ganesan, Narayana Murthy, Barij Nayan Sinha, Dominique Besson, Venkatesan Jayaprakash. Biological evaluation of 2aminothiazole hybrid as antimalarial and antitrypanosamal agents: Design and synthesis. Anti-Infective Agents (Communicated manuscript ID: BMS-AIA-2018-32). 21. Saravanabhavan Munusa, Vishnu N. Badavath, M. Sekar, Shabbir Muhammad. Microwave assisted synthesis, biological evaluation and molecular docking studies of novel pyrido[2,3a]carbazole derivatives (To be communicated) 22. Vishnu N. Badavath, Venkatesan Jayaprakash, B. N. Sinha. Design, Synthesis and Molecular Modeling of 2-benzylidenebenzofuran-3 (2H)-one derivatives against Chikungunya virus. (To be communicated) 23. Vishnu Nayak Badavath, Venkatesan Jayaprakash, Barij N. Sinha, Susanta K. Mondal. Curcumin-based Ferulic Acid Amides and Pyrazoline Analogues: In-Vitro Permeability and Metabolic stability studies. (To be communicated) 24. Vishnu N. Badavath, Venkatesan Jayaprakash, Barij N. Sinha, MAO inhibitory activity of 4, 5- dihydro-1H-pyrazole derivatives: Review. (To be communicated) 25. S. S. Jadav, Vishnu N. Badavath, Gulberk Ucar, Barij N. Sinha, Venkatesan Jayaprakash. Synthesis and MAO inhibitory activity of hybrid molecules: Pyrazoline with Rhodamine (To be communicated) Dr. Vishnu Nayak B AICTE-QIP Programme attended: 1. Certificate of Participation in AICTE-QIP-2012, Organized by Dept. of Pharm. Sci. & Tech. (UGC-SAP & DST-FIST Supported Dept.) Birla Institute of Technology (BITMesra), Ranchi- 835215, India. 2. Certificate of participation in AICTE-QIP-2011, Organized by Dept. of Pharm. Sci. & Tech. (UGC-SAP & DST-FIST Supported Dept.) Birla Institute of Technology (BITMesra), Ranchi- 835215, India. Poster Presentation at International Conference 1. Vishnu Nayak Badavath, Baysal I, Venkatesan Jayaprakash, Barij N. Sinha, Gulberk Ucar MAO inhibitory activity of 2-methoxy-4-(3-phenyl-4, 5-dihydro-1H-pyrazol-5-yl) phenol derivatives. International Conference on Nature Inspired Initiatives in Chemical Trends Organic Synthesis-Sep. 19-20, 2016, Organized by CSIR-Indian Institute of Chemical Technology, Hyderabad. 2. Vishnu Nayak Badavath, Design, synthesis and biological screening of monoamine oxidase inhibitors. Psychology, Autism and Alzheimer's disease. Sep. 30 - Oct. 01, 2013 Hilton San Antonio Airport, TX, USA (Accepted abstract). 3. Vishnu Nayak Badavath, Venkatesan J, B. N. Sinha, Gulberk U. Human MAO inhibitory activity of 2-(arylmethylidene)-2, 3-dihydro-1-benzofuran-3-one derivatives. International Conference on Nature Inspired Initiatives in Chemical Trends Organic Synthesis- Sep. 1920, 2016, Organized by CSIR-Indian Institute of Chemical Technology, Hyderabad, India. 4. Venkatesan Jayaprakash, Vishnu Nayak Badavath, B. N. Sinha, Ipek Baysal, Gulberk Ucar, S. K. Mondal, MAO inhibitory activity and Pharmacokinetic properties of Curcumin analogue AC1. International Multidisciplinary Symposium on Drug Research & Development, Organized by Faculty of Anadolu University & Society of Researchers in Pharmacy and Medicine (ILARUD), Eskisehir, Turkiey. Oct 15-19,2015 Poster Presentation at National Conference 1. Vishnu Nayak Badavath, S. K. Mondal, B. N. Sinha, Venkatesan Jayaprakash "Curcuminbased Ferulic Acid Amides and Pyrazolines Analogues: In-Vitro Permeability and Metabolic stability studies" Conference on Innovations in Pharmaceutical Technologies & Workshop on GLP/GMP Compliance, on 24-25 Jan. 2017, at NIPER-Hyderabad, Telangana, India. 2. Vishnu Nayak Badavath, T. Narender, K. Venkateswarlu "Microwave assisted preparation th Dr. Vishnu Nayak B of Chromene intermediate and their utilization in the synthesis of Chromenochalcones" Symposium on Medicinal Chemistry & Pharmaceutical Sciences, on 3-5, Mar. 2011. Organized by 3 CDRI-NIPER-Raebareli held at CSIR-CDRI, Lucknow, India. 3. Vishnu Nayak Badavath, "SIRTUINS?? the Potential Therapeutic Drug Target" on 25-27th, Mar. 2010, in 2 CDRI-NIPER-Raebareli symposium on Medicinal Chemistry & Pharmaceutical sciences held at (CSIR-CDRI), Lucknow, India. 4. Vishnu Nayak Badavath, C. Hanish Singh, V. Alagarsamy, "Monoamine Oxidase Inhibitory Effect of Evolvulusalsinoides Linn in Neurodegenration Induced Mice" on 27-28, Feb. 2009. Organized by AICTE Sponsored National Conference on Emerging Trends in Pharmaceutical Science, held at MNR College of Pharmacy, Sangareddy, Telangana, India. Workshop attended: 1. Participated in Workshop on Innovations in Pharmaceutical Technologies & GLP/GMP Compliance, on 24-25 Jan. 2017, at NIPER-Hyderabad, Telangana, India. 2. Participated in the TEQIP-sponsored workshop on "Software in Chemical Science Education and Research (SCR-2013)" conducted by the Dept. of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, on 3rdOct.2013. 3. Participated in seminar on "Intellectual property and Innovation Management in Knowledge Era" Organized by National Research Development Corporation, New Delhi (NRDC) and BIT, Mesra on 21stFeb, 2012 at Mesra, Ranchi, Jharkhand, India. 4. Participated in Work Shop On "Intellectual Property Rights (IPR-2011) on 2 Dec, 2011. At Birla Institute of Technology (BIT)-Mesra, Ranchi, Jharkhand, India. 5. Participated in "International Work Shop on Recent Trends in Intellectual Property Practice & Management" held at Central Drug Research Institute, Lucknow, India. Organized by CSIR & United States Patents & Trademark Office (5-6 Oct.2010). th nd th nd rd Guided by the available literature, and computational studies, the objective of the current research was to synthesize a few compounds incorporating the structural features of curcumin and to evaluate them for any improvement in MAO inhibitory activity, permeability and metabolic stability compared with curcumin. Plan of work The detailed plan of work to develop new selective and reversible MAO-inhibitors includes * Complete literature survey and its update on regular basis. * Synthesis and characterization of designed molecules through 1H NMR, 13C NMR and ESI - MS etc., Dr. Vishnu Nayak B * Biological screening of synthesized compounds for their human MAO inhibitory activity using in vitro enzyme assay methodology * Evaluation of permeability and metabolic stability of potent compounds through in vitro assay methodology * Carrying out molecular docking simulation for understanding the factors contributing towards potency and selectivity between the isoforms. * Documentation and Compilation of thesis. Dr. Vishnu Nayak B Scheme 1. Reagents and conditions: (a) CH2 (COOH) 2, C5H5N, CH3C6H5, NH2C6H5, reflux, 4 h (b) Ac2O, DMAP, 0-10 oC, 4 h (c) Dry DCM, DMF, (COCl) 2, 0 oC, 2h (d) Dry DCM, 28% aq.NH3, 0 oC, 30 min (e) 28 % NaOMe in MeOH, 15 min, 0 oC (f) TEA, Dry DCM, R-NH2, 0 oC, 2 h (g) 4% NH2NH2. H2O in CH3CN, 15-30 min, rt (h) Pyrrolidine, Dry DCM, 0 oC, 2 h (i) Morpholine, Dry DCM, 0 oC, 2 h (j) HMDS, dry DCM, TEA, reflux, 6 h. Scheme 2. Reagents and conditions: (a) NH2NH2.H2O, AcOH, reflux, 4 h (b) C6H5-NH-NH2, EtOH, NaOH, reflux, 4 h (c) NH2-NH-C(=X)-NH2, ethanolic NaOH, reflux, 6-12 h (d) NH2NH2.H2O, EtOH, reflux, 6 h (e) C6H5COCl, C5H5N, reflux, 3 h (f) C6H5-NCS, EtOH, reflux, 2 h (g) R-C6H4-SO2Cl, THF, 20 min, 10 - 15 oC (h). Cl-CO-OR, K2CO3, EtOH, 30 min, <10 oC. Dr. Vishnu Nayak B Scheme 3. Reagents and conditions: (a). NH2NH2.H2O, AcOH, reflux, 4 h (b) C6H5-NH-NH2, EtOH, NaOH, reflux, 4 h (c) NH2-NH-C(=X)-NH2, ethanolic NaOH, reflux, 6-12 h (d) NH2NH2.H2O, EtOH, reflux, 6 h (e) C6H5COCl, pyridine, reflux, 3 h (f) C6H5-NCS, EtOH, reflux, 2 h (g) p-CH3C6H4SO2Cl, THF, 20 min, 10 - 15 oC (h) Cl-CO-OR, K2CO3, EtOH, 30 min, <10 oC. Biochemical activities Determination of hMAO-A and hMAO-B activities: Compounds 1-36 were screened for their hMAO inhibitory activity using recombinant human MAO isoforms. MAO inhibitory activity was determined by measuring the production of H2O2 from p-tyramine, the common substrate for both hMAO-A and hMAO-B, using the Amplex-Red MAO assay kit. Selectivity of compounds towards hMAO-B has been calculated by using the formula given below ( ( ) ) SI = Selectivity Index for hMAO-B inhibition Ki = Inhibitory constant Dr. Vishnu Nayak B The interactions of the synthesized compounds (1-36) with hMAO isoforms were determined by a ?uorimetric method as described and modi?ed previously. Kinetic experiments and Reversibility experiments: The synthesized compounds were dissolved in DMSO with a maximum concentration of 1% (w/v) and used in the different concentration range. Protein was determined according to Bradford using bovine serum albumin as the standard. Reversibility was assessed using a centrifugation-ultra filtration method, previously reported Molecular docking simulation In order to understand the interaction at molecular level, compounds 1-36 were docked with Xray crystal structure of hMAO-A (PDB: 2BXR) and hMAO-B (PDB:2BYB) using AutoDock4.2. Analysis of docking results was done using MGL Tools-1.5.6 (The Sripps Research Institute). Top scoring molecule in the largest cluster was analysed for its interaction with the protein. Figure 3. Interaction of Compound 13 with hMAO-B (PDB: 2BYB) active site, H-bonds are shown as green dots. Figure 4. Interaction of Compound 14 with hMAO-B (PDB: 2BXR) active site, H-bonds are shown as green dots and ?-? interaction as yellow cylinders. Dr. Vishnu Nayak B Figure 5. Interaction of R-enantiomer of compound 24 with hMAO-A (PDB: 2BXR) active site, H-bonds are shown as green dots and ?-? interaction as yellow cylinders. Figure 6. Interaction of S-enantiomer compound 24 with hMAO-A (PDB: 2BXR) active site, H-bonds are shown as green dots and ?-? interaction as yellow cylinders. Figure 7. Interaction of R-enantiomer of compound 34 with hMAO-A (PDB: 2BXR) active site, H-bonds are shown as green dots and ?-? interaction as yellow cylinders. Dr. Vishnu Nayak B Figure 8. Interaction of S-enantiomer of compound 34 with hMAO-A (PDB: 2BXR) active site, ?-? interaction as yellow cylinders. In vitro permeability studies and metabolic stability study: Table . In vitro Caco-2 permeability study data of compounds Avg Papp ×10-6 cm/sec n=2 Permeability MAOCompound Efflux Ratio Rank selectivity A to B B to A (B>A/A>B 7.0 14.3 2.05 High Non-selective 6 19.1 51.2 2.7 High MAO-B 10 6.1 19.3 3.16 High MAO-B 13 0.0 8.8 Low MAO-A 14 11.7 16.8 1.43 High Non-selective 19 14.9 28.0 1.9 High MAO-B 20 9.6 16.5 1.72 High MAO-A 23 7.9 14.4 1.82 High MAO-A 24 4.1 6.3 1.55 Low MAO-A Ferulic acid 0.0 0.0 Low MAO-A Curcumin -6 All permeability values are represented as Avg Papp ×10 cm/sec, Permeability ranking based on following criteria (in-hours) Low: Papp A-B < 5×10-6 cm/sec, High: Papp A-B ? 5×10-6 cm/sec. Table. In vitro Human liver microsomal stability study data of compounds. T1/2 CLint, app Compounds (min) (µl/min/mg) 85.4 16.22 6 308.0 4.5 10 50.1 27.68 13 11.4 121.80 14 11.4 121.70 19 42.0 33.0 20 21.2 65.27 23 19.0 73.40 24 120.0 11.60 Ferulic acid 7.7 180.33 Curcumin CLint, app range: 11.6 - 462.0 µL/min/mg, T-1/2range: 3-120 min, LM conc: 0.5mg/mL. Dr. Vishnu Nayak B Compounds (6, 10, 13, 14, 19, 20, and 23-24) synthesized (by Scheme 1 and 2) were subjected in vitro permeability studies (Caco-2), and metabolic stability studies. Structural activity relationship (SAR) Dr. Vishnu Nayak B Dr. Vishnu Nayak B Summary and conclusion: This section consists of summary and conclusion of results obtained by the experimental work. First series of compounds were designed by considering half the structure of curcumin. They were ferulic acid amides (1-14). Compound 14 was actually a bis-feruloyl amide that mimics curcumin. They were evaluated for their hMAO-isoform inhibitory activity. All the compounds were found to inhibit either of hMAO isoforms selectively or non-selectively. Most of the compounds were found to be selective towards hMAO-B, except compounds 3-6 that are non-selective and compound 14 selective towards hMAO-A. Compound 14 was found to have improved activity and metabolic stability compared with curcumin, but there is no significant improvement in permeability. On the other hand the mono-feruloyl derivative 13 was found to be potent and selective towards hMAO-B with significant improvement in permeability and metabolic stability. In the second series we designed a cyclic analogue of the ? ?- unsaturated portion of curcumin to provide a novel pyrazoline 15-26, and were evaluated for their hMAO inhibitory activity. Ten compounds 15 - 18 and 21-26) were found to be selective towards hMAO-A, while one (compound 20) was found to be selective towards hMAO-B and another (19) was found to be non-selective. Compound 20 was having the best permeability and metabolic stability amongst the four studied that was followed by compounds 19, 23 and 24. The design strategy adopted that of improved the permeability and metabolic stability characteristics significantly in comparison with curcumin. Dr. Vishnu Nayak B In the third series we designed few chalcone that resembles aryl-?, ?-unsaturated carbonyl portion of curcumin but by reversing the position of the double bond and the carbonyl group. These derivatives were then cyclized to provide a series of novel pyrazoline derivatives 27-36. Eight compounds 27-29 and 32-36) are found to be potent, selective, competitive and reversible inhibitor of hMAO-A, while compound 31 was found to be a selective inhibitor of hMAO-B, and another compound 30, was found to be no-selective. Dr. Vishnu Nayak B iii). Work carried out during Post graduation As a Project Research Assistant. Project supervisor: Dr. T. Narender, Principal Scientist in Medicinal and Process Chemistry Division at CSIR-Central Drug Research Institute-Lucknow under master degree project. Period: 1 Year (June-2010 June 2011 * Synthesis of novel N-(2-hydroxy-2-p-tolylethyl)-amideand N-(2-oxo-2-p- tolylethyl)-amide derivatives and their Antidyslipidemic activity In Triton induced Hyperlipidemiamodel. Reagents and conditions: a). NaN3, MeOH, H2O (b). 10% Pd/C, ConcHCl, Dry MeOH (c). Acids, DIC, DIPEA, Dry DCM, 0o C, rt (d). NaBH4, MeOH * New chemical access has been developed for the synthesis of 3?-acetyl-4?hydroxychalcones from 2-hydroxy-4-acyl-acetophenone [1,1'-(4-hydroxy-1,3-phenylene) diethanone] and various substituted aromatic aldehydes by a regioselectiveClaisen-Schmidt condensation reaction using BF3.Et2O, in good to excellent yields within 12-24 hrs. O HO F O B BF3-Et2 O O F F F O B O H O R O O BF3 O H O HO -H 2O O F O F B O HO R O Dr. Vishnu Nayak B * Microwave assisted preparation of Chromene intermediates and their utilization in the synthesis of Chromenochalcones Natural product isolation * Extracted novel Limonoids from Xylocarpusmolluccensis, * Isolated 4-hydroxyisoleucine an unusual amino acid from Trigonella foenum graecum (methi seeds) exhibits dual activity (antidyslipidemic and antihyperglycemic).
Description
