Research Area:   “Organic Synthesis and Medicinal Chemistry”

• New Method Development (C-H Functionalization Reactions): Application in the Synthesis of Bio-actives and Natural products

C-H functionalization reactions via free-radical reactions provide a unique opportunity for the synthesis of C-C, C-N, C-O, C-S bond formation. Our group is exploiting this approach for the development of new methodology as well as late-stage functionalization and synthesis of bio-actives and natural products.

(Selected Publications: J. Org. Chem.  2020, 85, 716; Eur. J. Org. Chem. 2019, 3591; J. Org. Chem., 2018, 83 12420; J. Org. Chem., 2017, 82, 1000; Org. Lett. 2016, 18, 3638; J. Org. Chem. 2016, 14, 5886; Org. Biomol. Chem. 2016, 14, 4312; Org. Lett. 2015, 17, 5547; Org.Biomol.Chem. 2015, 13, 11341; Eur. J. Org. Chem. 2015, 6526-6533; J. Org. Chem. 2015, 80, 1929; RSC Adv. 2014, 4, 50208; J. Org. Chem. 2013, 78, 2639)

• Medicinal Chemistry in the area of Infection and Oncology

Drug discovery has high attrition rate and majority of the failure is because of poor drug-like properties and labilities issues of genotoxicity, mutagenicity etc. Our group is working on the identification of new lead-like candidates in the area of infection, oncology and inflammation.  Our efforts have led to the identification of anti-infective and anti-cancer leads and few are now being investigated in pre-clinical studies.

(Selected Publications: J. Med. Chem., 2018, 60,  9470; Nature Communications  2018, 9, 4217; Drug Discovery Today, 2018, 23, 605; Tuberculosis, 2018, 108, 56–63; Pulm. Pharmacol Ther. 2018, 48, 151; ACS Med. Chem. Lett. 2015, 6, 1041; ACS Med. Chem. Lett. 2015, 6, 1059; Org. Biomol. Chem. 2015, 13, 3610; PLoS ONE, 2014, 9, e110411; Med. Chem. Commun. 2014, 5, 521-527; Chem. Rev. 2013, 113, 6761–6815)

• Carbohydrate Chemistry (GPI anchor and Phospholipids based Probes)

Glycosylphosphatidylinositols (GPIs) and GPI-anchored proteins along with cholesterol and sphingolipids create functional micro-domains (lipid rafts) as signaling platforms at the cell surface. The molecular understanding of the mechanism of the localized clustering of GPI-anchored proteins and cholesterol in lipid rafts requires synthetic probes based on GPI structures and Phospholipids. A collaborative Programme with NCBS, Bangalore (Prof. Satyajit Mayor’s group) is going on to elucidate the structural role of GPIs and Phospholipids in clustering of cholesterol-rich ordered domains, where the challenging synthesis of fluorescently labelled and metabolically stable probes is of focus of interest of our group.

(Selected Publications: J. Org. Chem.  2020, 85, 7757; J. Org. Chem. 2015, 80, 11916; Cell, 2015, 161, 581; Org. Biomol. Chem. 2014, 12, 1163-1172)

• Natural Product Chemistry (Isolation, Synthesis and Phytopharmaceutical drugs development)

Natural products are always being an inevitable source of new therapeutic drugs, however, has been least focussed in last two decades because of many reasons starting from their availability, booms of synthetic chemistry, high-throughput and combinatorial chemistry etc. The issue of liabilities and high attrition rate has again attracted interest and is being exploited to those areas which are ignored in the past. One such example is phytocannabinoids, a unique class of compound found in cannabis crop, which is being less pursued in the past because of their poor drug-like properties and restriction because of its psychoactivity and NDPS Act. The seldom work in this area in last few decades has brought the clear understanding regarding its psychoactivity and therapeutic potential and presenting a reason for bringing this into main stream drug discovery. In India, cannabis grows all over India as weed, there is an emergent great opportunity to explore this valuable plant for the production of non-psychotic phytocannabinoids and explore their potential for biomedical applications. Recently, CSIR-IIIM has sought approval from regulatory authority regarding the R&D of cannabis for therapeutic potential. As  our group is working in the drug discovery and have initiated extensive research programme on cannabis crop to utilize its full potential i) development of phytopharmaceutical based drugs; ii)  development of synthetic route for the phytocannabinoids; iii) Creation of database for Cannabis accessions from different geographical region; iv) Creation of repository of chemical constituents of Cannabis as most phytocannabinoids still await an evaluation of their biological profile and pharmaceutical potential.

• Lead optimization of identified anti-TB chemotypes to develop novel pre-clinical candidate: Synthesis, In vitro, Structure-activity relationship, Pharmacokinetics and In vivo evaluation (3 Years, 2018-2021, GAP2181, DST/SERB Funded)
• Genotype-Phenotype relationship in rare genetic disorder: Physiochemical analysis of mutations in GNE myopathy nad phenotypic modulation by small molecule effector (3 Years, 2017-2020, GAP2171, DBT Funded)
• COVID-19 API Mission (9 Months, HCP-29, June 2020-Mar 2021, CSIR Funded).
• R&D on cannabis (Isolation, testing, Synthesis and Medicinal Chemistry) (CSIR-IIIM RC Approved, MLP1001)
• Medicinal chemistry of natural products for cancer, malaria and M. tuberculosis drug discovery (CSIR-IIIM RC Approved, MLP 5005)
• Chemistry of glycoconjugates; new opportunities for basic biology (CSIR-IIIM RC Approved, MLP 4016)