Natural Products & Medicinal Chemistry (NPMC)

The research focus of the department is to discover natural products driven discovery of small molecule lead candidates as a potential treatment for unmet medical needs. The therapeutic areas currently under focus are cancer (particularly breast and ovarian cancer), Alzheimer’s disease, infectious diseases (tuberculosis, gram-negative infections, viral infections), sickle cell anaemia, and rheumatoid arthritis. The department has strong expertise in natural products chemistry, synthetic organic chemistry (small molecules, carbohydrates, peptides), total synthesis of complex natural products, drug design/ molecular modelling, medicinal chemistry, phytopharmaceuticals/ nutraceuticals, etc. The research activities of the department are supported by the state-of-art analytical facilities available within the central instrumentation facility. The department has experience and expertise in preclinical development / IND enabling of lead candidates.

  • Drug discovery and development: To discover preclinical candidates (NCE’s & phytopharmaceuticals) for unmet medical needs, and take them to clinical trials.
  • Development of new chemistry, new processes for medicinally important natural products and drugs
  • Natural products chemistry – Isolation of secondary metabolites from plants, microbes and marine sources
  • Synthetic organic chemistry (small molecules, peptides, carbohydrates, nucleosides)
  • Total synthesis of complex natural products
  • Computational chemistry/ drug design
  • Medicinal chemistry/ lead optimization
  • Phytopharmaceuticals/ nutraceuticals
  • All state-of-art equipments that are necessary for chemistry research such as rotary evaporators, vacuum pumps, chillers, magnetic stirrers, low temperature reaction baths, flash chromatography, microwave reactors, HPLC systems, etc are available within the department. The departmental research activities are supported by state-of-art analytical facilities available within the central instrumentation facility.
  • Linux HP workstations (Intel Xeon Dual Core Processor) with the software suite Schrodinger installed

Following are the instruments which are being used for various kind of analysis:

List of current ongoing projects

Sr No Ongoing Projects Funding agency
CSIR Mission Projects
1. CSIR-Sickle-Cell Anaemia Mission Phase –II CSIR
2. CSIR-Aroma Mission-II CSIR
Other CSIR funded Projects
3 Evaluation of the role and mechanism of Rifampicin and its analogues in alleviating hyperglycaemia related complication CSIR
4 Repurposing of colchicine for management of COVID-19 patients CSIR
5 Preclinical development of crocin-1 enriched Crocus sativus as phytopharmaceutical lead CSIR
6 Synergizing marine ecology with bioprospecting: Harnessing marine living resources for products and bioprocesses CSIR
7 Preclinical development of small molecule(s) promoting hair regeneration and studying mechanism of hair regenerations CSIR
8 Non-infringing routes for the synthesis of FDA approved life saving drugs CSIR
9 Nucleoside as biofilm inhibitors of bacteria and to understand the underlying mechanism of action CSIR
10 Development of -Hairpin Peptidomimetics and Self-Assembled Ultrashort Hybrid Peptide Nanostructures as Anti-Infective Agents CSIR
11 Isolation Synthesis of Bioactive Molecules from Microbial Sources CSIR
Externally funded projects
12 Development nutraceutical products from algae Industry Sponsored
13 Synthesis of Reference Standards and in-vitro and in-vivo studies (PK studies) on the metabolites and long-term metabolites NDTL
14 Nitric oxide-Cannabidiol conjugates: A dual action hybrids for pain management in sickle cell anaemia SERB
15 Lead optimization of identified anti-TB chemotypes to develop novel pre-clinical candidate: Synthesis, In vitro, Structure-activity relationship, Pharmacokinetics and In vivo evaluation SERB
16 Design & synthesis of andrographolide analogues for identification of potent anti-cancerous hit SERB
17 CBD-THC Enriched Phytopharmaceutical drug for cancer pain management DBT
18 Phytopharmaceutical Development of Ficus semicordata Buch.-Ham. Ex  Sm. as per regulatory guidelines of DCGI (under the phytopharmaceutical Mission for North East Region DBT
19 Genotype Phenotype relationship in rare genetic disorders:  Physiochemical analysis of mutations in GNE Myopathy and Phenotypic modulation by small molecule effectors  

DBT

Authors Title Journal
Computational chemistry
Akhoon BA, Choudhary S, Tiwari H, Kumar A, Barik MR, Rathor L,  Pandey R, Nargotra A. Discovery of a new donepezil-like acetylcholinesterase inhibitor for targeting Alzheimer’s disease: computational studies with biological validation J. Chem.  Inf. Model. 2020; 60(10):4717-4729
Mahajan P, Wadhwa B, Barik MR, Malik F, Nargotra A. Combining ligand- and structure-based in silico methods for the identification of natural product-based inhibitors of Akt1. Mol Divers, 2020; 24(1):45-60

 

Abdullaha M; Ali M; Kour D; Kumar A; Bharate SB Discovery of Benzo[cd]indol-2-one and Benzylidene-thiazolidine-2,4-dione as New Classes of NLRP3 Inflammasome Inhibitors via ER-β Structure Based Virtual Screening Bioorg. Chem, 2020, 95, 103500
Natural Products Chemistry
Ntemafack A; Nuthakki V; Abdullaha M; Qazi H; Gandhi SG; Bharate SB. Discovery of Helminthosporin, an Anthraquinone Isolated from Rumex abyssinicus Jacq as a Dual Cholinesterase Inhibitor ACS Omega, 2020, 5 (3), 1616-1624

 

Bhatt S, Kumar V, Dogra A, Ojha PK, Wazir P, Sangwan PL, Singh G, Nandi U. Amalgamation of in-silico, in-vitro and in-vivo approach to establish glabridin as a potential CYP2E1 inhibitor

 

Xenobiotica. 2021 Feb 15:1-11
Medicinal chemistry
Dheer D, Behera C, Singh D, Abdullaha M, Chashoo G, Bharate SB, Gupta PN, Shankar R. Design, synthesis and comparative analysis of triphenyl-1, 2, 3-triazoles as anti-proliferative agents Eur. J. Med. Chem., 2020, 207, 112813

 

Abdullaha M; Nuthakki VK; Bharate SB. Discovery of methoxy-naphthyl linked N-(1-benzylpiperidine) benzamide as a blood-brain permeable dual inhibitor of acetylcholinesterase and butyrylcholinesterase Eur. J. Med. Chem., 2020, 207, 112761

 

Rath SK, Singh S, Kumar S, Wani NA, Rai R, Koul S, Khan IA, Sangwan PL. Synthesis of (E)-3-(1-chloro-3,4-dihydronaphthalen-2-yl)acrylic acid substituted amino acid ester derivatives as inhibitors of Staphylococcus aureus NorA efflux pump to combat antimicrobial resistance. Bioorg. Med. Chem. 2020, 27(2). 343-353
Nuthakki VK; Yadav RR; Bharate SB. Identification of Aplysinopsin as a Blood-brain Barrier Permeable Scaffold for Anti-cholinesterase and Anti-BACE-1 activity Bioorg. Chem. 2021, 107, 104568

 

New Synthetic Methods/ Total synthesis
Kumar M, Ahmed R, Singh M, Sharma S, Thatikonda S, Singh PP. Functionalization of Alkynes and Alkenes Using a Cascade Reaction Approach: Synthesis of β-Keto Sulfones under Metal-free Conditions J Org Chem,  2020, 85(2):716-725
Gangadurai C, Illa GT, Reddy DS. FeCl 3-catalyzed oxidative decarboxylation of aryl/heteroaryl acetic acids: preparation of selected API impurities

 

Org Biomol Chem. 2020 Nov 7;18(41):8459-8466
J. Kumar, A. Ahmad, M.A. Rizvi, B.A. Shah Photoredox-Mediated Synthesis of Functionalized Sulfoxides from Terminal Alkynes Org. Lett. 2020, 22, 5661–5665
Athawale PR, Kalmode HP, Motiwala Z, Kulkarni KA, Reddy DS. Overturning the Peribysin Family Natural Products Isolated from Periconia byssoides OUPS-N133: Synthesis and Stereochemical Revision of Peribysins A, B, C, F, and G

 

Org Lett. 2020 Apr 17;22(8):3104-3109
Kour J, Venkateswarlu V, Verma PK, Hussain Y, Dubey G, Bharatam PV, Sahoo SC, Sawant SD. Oxone-DMSO Triggered Methylene Insertion and C(sp 2)-C(sp 3)-H-C(sp 2) Bond Formation to Access Functional Bis-Heterocycles

 

J Org Chem. 2020 Apr 3;85(7):4951-4962
Carbohydrate chemistry
Bhardwaj M, Hussain N, Zargar IA, Dash AK, Mukherjee D. Synthesis of aryl ethers of carbohydrates via reaction with arynes: selective O-arylation of trans-vicinal dihydroxyl groups in carbohydrates Org Biomol Chem. 2020 Jun 10;18(22):4174-4177
Peptide chemistry
Shankar S, Singh G, Rahim JU, Qayum A, Sharma PR, Katoch M, Rai R. Investigation of α/γ hybrid peptide self-assembled structures with antimicrobial and antibiofilm properties

 

J Pept Sci. 2020 Apr;26(4-5):e3243
Ur Rahim J, Singh G, Shankar S, Katoch M, Rai R. Tetrahydropiperic acid (THPA) conjugated cationic hybrid dipeptides as antimicrobial agents

 

J Antibiot (Tokyo). 2021, ASAP.
Phytopharmaceuticals/ nutraceuticals
Kumar V; Bharate SS; Bhurta D; Gupta M; Gandhi SG; Singh D; Jaglan S; Kumar A; Vishwakarma RA; Bharate SB Evaluation of rohitukine-enriched fraction of Dysoxylum binectariferum Hook.f. (leaves) as Anti-arthritic Phytopharmaceutical Candidate: Chemical Standardization, In-vivo validation, Formulation Development and Oral Pharmacokinetics J. Ethnopharmacol., 2020, 254, 112758
Recent reviews/ perspectives
Raghuvanshi R.; Bharate SB. Recent developments in the use of kinase inhibitors in management of viral infections J. Med. Chem.  2020, ASAP
Gunjal VB, Thakare R, Chopra S, Reddy DS. Teixobactin: A Paving Stone toward a New Class of Antibiotics?

 

J Med Chem. 2020 Nov 12;63(21):12171-12195
Bag D, Verma PK, Sawant SD. Chiral Transient Directing Group Strategies in Asymmetric Synthesis. Chem Asian J. 2020 Oct 16;15(20):3225-3238
Bag D, Sawant SD Heteroarene-tethered Functionalized Alkyne Metamorphosis Chemistry, 2021, 27, 1165-1218
Bag D, Kour H, Sawant SD. Photo-induced 1,2-carbohalofunctionalization of C-C multiple bonds via ATRA pathway

 

Org Biomol Chem. 2020 Nov 7;18(41):8278-8293
Shankar S, Junaid Ur Rahim, Rai R. Self-Assembly in Peptides Containing β-and γ-amino Acids. Curr Protein Pept Sci. 2020; 21(6):584-597.
Ahmad Dar A, Sangwan PL, Kumar A. Chromatography: An important tool for drug discovery. J Sep Sci. 2020 Jan;43(1):105-119