Arindam Talukdar , Ph.D.

Principal Scientist
Organic & Medicinal Chemistry
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Research Interest

Our lab aims to answer fundamental questions that lie at the interface of chemistry and biology by integrating the concept of organic chemistry, biochemistry and molecular modeling to perform structure-based design and synthesis of novel chemical entity to unravel the molecular mechanism and develop potential treatment for human diseases.

Probing Endosomal Toll-like Receptors (TLRs). TLRs are members of the larger family of evolutionarily conserved pattern recognition receptors which are critical first line of defence for self-nonself discrimination by the host immune response. Aberrant endosomal TLR activation is implicated in autoreactive inflammation in different autoimmune diseases. The goal is to rationally design selective inhibitors for the nucleic acid-recognizing TLRs for devising novel therapeutic strategies in relevant clinical contexts. 

Epigenetic modifying enzymes as novel therapeutic targets: The main focus is to perform structure-based design and synthesis of small-molecule regulators of epigenetics modifying enzymes such as histone methyltransferases (HMT) as tools to unravel the complex biology of epigenetics and contribute towards epigenetic-based drugs for the treatment of a number of diseases such as cancer, autoimmunity, diabetes, or neurological disorders.

Credentials

  • Senior Research Scientist (2010-2012), Albany Molecular Research Inc. Singapore
  • Post-doctoral Research Associate (2005-2009), Purdue University, USA (Prof. Mark Cushman).
  • Post-doctoral Research Scholar (2004-2005), The Ohio State University, USA (Prof. Peng George Wang).
  • M.Pharmacy (1997) Medicinal Chemistry, Panjab University, Chandigarh, India (Prof. Tilak Raj Juneja).

Patents & Publications

PATENTS

  1. Quinazolinones Derivatives for Treatment of Non-Alcoholic Fatty Liver Disease, Preparation And Use Thereof.  PCT/IN2021/050621.
  2. Bicycle Topoisomerase I Inhibiting Compounds, Process For Preparation And Use Thereof. WO2019229765.  
  3. Purine Based Compounds As Toll-Like Receptor 9 Antagonist. WO/2019/092739, US 2020/034706. 
  4. Bicyclic Compound and Use Thereof for Inhibiting SUV39H2. PCT/US2016/0051350. 
  5. Blocking toll-like receptor 9 signaling with small molecule antagonist. WO2017/163264A1, US10662177B2. 
  6. Preparation of 2,5-disubstituted pyrrolidines and tetrahydrothiophenes as leukotrine biosynthesis inhibitors. WO2000001670 A1, EP 1115702. 

 

PUBLICATIONS

  1. Kundu B, Raychaudhuri D, Mukherjee A, Sinha BP, Sarkar D, Bandopadhyay P, Pal S, Das N, Dey D, Ramarao K, Nagireddy K, Ganguly D,* and Arindam Talukdar*. Systematic Optimization of Potent and Orally Bioavailable Purine Scaffold as a Dual Inhibitor of Toll-Like Receptors 7 and 9. Journal of Medicinal Chemistry, 2021 (In Press).
  2. Arindam Talukdar,* Ganguly D, Roy S, Das N, Sarkar D. Structural Evolution and Translational Potential for Agonists and Antagonists of Endosomal Toll-like Receptors. Journal of Medicinal Chemistry, 2021, 64, 12, 8010.
  3. Pal S, Paul B, Bandopadhyay P, Preethy N, Sarkar D, Rahaman O, Goon S, Roy S, Ganguly D,* Arindam Talukdar*. Synthesis and characterization of new potent TLR7 antagonists based on analysis of the binding mode using biomolecular simulations. European Journal of Medicinal Chemistry, 2021, 210, 112978. 
  4. Bezerra GA, Holenstein A, Foster WR, Xie B, Hicks KG, Bürer C, Lutz S, Mukherjee A, Sarkar D, Bhattacharya D, Rutter J, Arindam Talukdar, Brown PJ, Luo M, Shi L, Froese DS,* Yue WW.* Identification of small molecule allosteric modulators of 5,10-methylenetetrahydrofolate reductase (MTHFR) by targeting its unique regulatory domain. Biochimie, 2021. 183, 100. 
  5. Kundu B, Sarkar D, Chowdhuri SP, Pal S, Das SK, Das BB, and Arindam Talukdar*. Development of a metabolically stable topoisomerase I poison as anticancer agent. European Journal of Medicinal Chemistry, 2020, 202, 112551.
  6. Mukherjee A, Raychaudhuri D, Sinha BP, Kundu B, Mitra M, Paul B, Bandopadhyay P, Ganguly D,* and Arindam Talukdar*. A Chemical Switch for Transforming a Purine Agonist for Toll-like Receptor 7 to a Clinically Relevant Antagonist. Journal of Medicinal Chemistry, 2020, 63, 4776.
  7. Bhowmik D, Pal S, Lahiri A, Arindam Talukdar*, Sandip Paul*. Emergence of multiple variants of SARS-CoV-2 with signature structural changes. 2020.  bioRxiv preprint. doi: 10.1101/2020.04.26.062471.
  8. Pal S, Arindam Talukdar*. Compilation of Potential Protein Targets for SARS-CoV-2: Preparation of Homology Model and Active Site Determination for Future Rational Antiviral Design. 2020. ChemRxiv. doi: 10.26434/chemrxiv.12084468. 
  9. Kundu B, Das SK, Paul Chowdhuri S, Pal S, Sarkar D, Ghosh A, Mukherjee A, Bhattacharya D, Das BB,* and Arindam Talukdar*. Discovery and Mechanistic Study of Tailor-Made Quinoline Derivatives as Topoisomerase 1 Poisons with Potent Anticancer Activity. Journal of Medicinal Chemistry, 2019, 62, 3428.
  10. A Mukherjee, S Mishra, NK Kotla, K Manna, S Roy, B Kundu, Bhattacharya D, Saha KD, Arindam Talukdar*. Semisynthetic Quercetin Derivatives with Potent Antitumor Activity in Colon Carcinoma. ACS Omega, 2019, 4, 7285.
  11. Kundu B, Sarkar D, Ray N, Arindam Talukdar*. Understanding the Riboflavin Biosynthesis Pathway for the Development of Antimicrobial Agents. Medicinal Research Reviews. 2019, 1-34. 
  12. Pal S, Kumar V, Kundu B, Bhattacharya D, Preethy N, Reddy MP, Arindam Talukdar*. Ligand-based Pharmacophore Modeling, Virtual Screening and Molecular Docking Studies for Discovery of Potential Topoisomerase I Inhibitors. Computational and Structural Biotechnology Journal, 2019, 17, 291.
  13. Paul B, Rahaman O, Roy S, Pal S, Satish S, Mukherjee A, Ghosh AR, Raychaudhuri D, Bhattacharya R, Goon S, Ganguly D* and Arindam Talukdar*. Activity-guided Development of Potent and Selective Toll-like Receptor 9 Antagonists.  European Journal of Medicinal Chemistry, 2018, 159, 187.
  14. Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR, Rahaman O, Arindam Talukdar, Ganguly D. Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation. Journal of Immunology. 2018. pii: ji1701118.
  15. S Roy, B Paul, A Mukherjee, B Kundu, Arindam Talukdar*. Copper-catalyzed selective C–N bond formation with 2-amino, 2-hydroxy and 2-bromo-5-halopyridine. RSC Advances, 2017, 7, 44366.
  16. Roy S, Mukherjee A, Paul B, Rahaman O, Roy S, Maithri G, Ramya B, Pal S, Ganguly D,* and Arindam Talukdar*. Design and Development of Benzoxazole Derivatives with Toll-like Receptor 9 Antagonism. European Journal of Medicinal Chemistry, 2017, 134, 334-347.
  17. Arindam Talukdar, Zhao Y, Lv W, Bacher A, B. Illarionov, M. Fischer, and Mark Cushman. O-Nucleoside, S-Nucleoside, and N-Nucleoside Probes of Lumazine Synthase and Riboflavin Synthase. J. Org. Chem., 2012, 77, 6239-6261.
  18. Mayhoub SA, Arindam Talukdar, and Mark Cushman. A Highly Efficient Oxidation of Benzyl Methyl Ethers with NBS Selectively Affords Either Aromatic Aldehydes or Aromatic Methyl Esters. J. Org. Chem., 2010, 75, 3507-3510.
  19. Arindam Talukdar, Morgunova E, Duan J, Meining W, Foloppe N, Nilsson L, Bacher A, Illarionov B, Fischer M, Ladenstein R, Mark Cushman. Virtual Screening, Selection and Development of a Novel Structural Scaffold for Inhibition of Lumazine Synthase. Bioorg Med Chem. 2010, 18, 3518-3534.
  20. Arindam Talukdar, Breen M, Bacher A, Illarionov B, Fischer M, Georg G, Ye QZ, and Mark Cushman. Discovery and Development of a Small Molecule Library with Lumazine Synthase Inhibitory Activity. J. Org. Chem., 2009, 74, 5123–5134 (Feature JOC Article).
  21. Arindam Talukdar, Illarionov B, Bacher A, Fischer M, Mark Cushman, Synthesis and enzyme inhibitory activity of the S-nucleoside analogue of the ribitylaminopyrimidine substrate of lumazine synthase and product of riboflavin synthase. J. Org. Chem., 2007,72, 7167-7175.
  22. Chen W, Xia C, Wang J, Thapa P, Li Y, Arindam Talukdar, Nadas J, Zhang W, Zhou D, Wang PG. Synthesis and Structure-Activity Relationship Study of Isoglobotrihexosylceramide Analogues. J. Org. Chem. 2007, 72, 9914-9923.
  23. Kim HY, Arindam Talukdar, and Mark Cushman, Regioselective synthesis of N--hydroxyethylaziridines by ring-opening reaction of epoxides with aziridine generated in situ.  Organic Letters, 2006, 8, 1085.
  24. Luo S, Zhu, L, Arindam Talukdar, Mi X, Cheng J-P, Wang PG. Recent Advances in Rear Earth-Metal Triflate catalyzed Organic Synthesis in Green Chemistry. Mini-Reviews in Organic Chemistry 2005, 2. 546.
  25. Zhu L, Arindam Talukdar, Zhang G, Kedenburg JP, Wang PG. A divergent synthesis of uncommon sugars from furanaldehyde. Synlett, 2005, 1547.
  26. Gurjar, MK, Arindam Talukdar. Synthesis of terminal disaccharide unit of Klebsiella pneumoniae. Tetrahedron, 2004, 60, 3267.
  27. Arindam Talukdar.* Unusual conversion of sugar oximes to sugar nitriles with ruthenium catalysts. Synthetic Communications, 2002, 32(22), 3503.
  28. Gurjar, MK, Arindam Talukdar. Heck reaction of (S)-N-Cbz-allyl glycine tert-butyl ester with aromatic halides. Synthesis, 2002, 315.
  29. Juneja, TR, Arindam Talukdar*, Gupta, RL. Mutagenicity of Sulfoscanate: a comparative study. Mutation Res., 2002, 518, 155-161.
  30. Chorghade MS, Gurjar MK, Arindam Talukdar. Fascinating Excursions into Chiral Chemistry: An Insider’s Perspective. CHIMICA OGGI Chemistry Today 2002, 20, 20.
  31. Juneja, TR, Arindam Talukdar*, Mehta N, Gupta, RL. Effect of various alkyl and unsaturated substituents on the mutagenicity of some nitrophenyl thioethers. Mutation Res., 2001, 495, 97-102.
  32. Gurjar MK, Sadalapure K, Adhikari S, Sarma BVNBS, Arindam Talukdar, Chorghade MS. Kinetic resolution of aryl glycidyl ethers: A practical synthesis of optically pure β-blocker (S)-Metoprolol. Heterocycles, 1998, 48, 1471.

 

BOOK CHAPTER

  1. Molecular Docking for Computer-Aided Drug Design. Chapter-21; Computational Approaches Toward Development of Topoisomerase I Inhibitor: A Clinically Validated Target. Arindam Talukdar, Sourav Pal. Elsevier. 2021
  2. Protein–Protein Interaction Regulators. Chapter-13; Small Molecule Modulators of Endo-lysosomal Toll-like Receptors. Arindam Talukdar, Ayan Mukherjee, Dipyaman Ganguly. Protein–Protein Interaction Regulators. Royal Society of Chemistry. 2020.
  3. N-Nitroso Compounds. Chapter-3; Nitric Oxide Donors and its Applications. Arindam Talukdar, Wang P. G. 2004. Wiley-VCH, Germany.