2. Academic Validation
  3. Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents

Synthesis and biological evaluation of novel bavachinin analogs as anticancer agents

  • Eur J Med Chem. 2018 Feb 10:145:511-523. doi: 10.1016/j.ejmech.2018.01.006.
Nidhi Gupta 1,  Arem Qayum 2,  Arun Raina 3,  Ravi Shankar 3,  Sumeet Gairola 4,  Shashank Singh 2,  Payare L Sangwan 5
Affiliations

Affiliations

  • 1 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.
  • 2 Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
  • 3 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
  • 4 Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India; Plant Science Division, CSIR-Indian Institute of Integrative Medicine Jammu, 180001, India.
  • 5 Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India. Electronic address: plsangwan@iiim.ac.in.
PMID: 29335212 DOI: 10.1016/j.ejmech.2018.01.006
Abstract

A library of 28 analogs of bavachinin including aliphatic and aromatic ethers, epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives have been synthesized and evaluated for cytotoxicity against four different human Cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for many analogs compare to bavachinin. Best results were observed for a 1,2,3-triazole analog (17i) with IC50 values 7.72, 16.08, 7.13 and 11.67 μM against lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) Cancer cell lines respectively. This analog showed three and four fold improvement in cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1). Structure activity relationship (SAR) study for all synthesized analogs was carried out. Further, mechanistic study of the lead molecule (17i) revealed that it inhibits colony formation and in vitro migration of human colon Cancer cells (HCT-116). Also, it induced the morphological changes and mediated the apoptotic cell death of HCT-116 cells with perturbance in mitochondrial membrane potential (MMP) and PARP cleavage.

Keywords

Bavachinin; Colony formation; Cytotoxicity; In-vitro migration; MMP; PARP.

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