2. Academic Validation
  3. Design, synthesis and comparative analysis of triphenyl-1,2,3-triazoles as anti-proliferative agents

Design, synthesis and comparative analysis of triphenyl-1,2,3-triazoles as anti-proliferative agents

  • Eur J Med Chem. 2020 Dec 1;207:112813. doi: 10.1016/j.ejmech.2020.112813.
Divya Dheer 1,  Chittaranjan Behera 2,  Davinder Singh 1,  Mohd Abdullaha 3,  Gousia Chashoo 4,  Sandip B Bharate 3,  Prem N Gupta 5,  Ravi Shankar 6
Affiliations

Affiliations

  • 1 Bio-organic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India.
  • 2 PK-PD Toxicology & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.
  • 3 Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India.
  • 4 Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India.
  • 5 PK-PD Toxicology & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India. Electronic address: pngupta@iiim.res.in.
  • 6 Bio-organic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India. Electronic address: rshankar@iiim.res.in.
PMID: 32947093 DOI: 10.1016/j.ejmech.2020.112813
Abstract

Herein, a series of triaryl-1,2,3-triazoles, in order to check cytotoxicity on breast Cancer cell lines have been synthesized with pendent benzyl ring to mimic the phenolic A ring of Tamoxifene. The biological results indicated that most of the compounds possessed comparative anti-proliferative activities in both ER + ve (MCF-7) and ER-ve (MDA-MB-231) breast Cancer cell lines. Among synthesized derivatives, five compounds 8f, 8i, 8j, 8n and 8p showed anti-proliferative activities at <5 μM against MCF-7 cell line and three compounds 8e, 8f and 8j show IC50 value greater than 30 μM in FR-2 cells (normal cell). Moreover, to understand the mechanistic behavior of the selective compound 8f, various studies performed viz. surface morphological changes by bright field microscopic examination, nuclear morphological alteration by DAPI staining, measurement of intracellular ROS level and determination of change in mitochondrial membrane potential. It was observed that, the selective compound 8f associated with higher ROS generation along with decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as reduction in number and shrinkage of cells coupled with nuclear blabbing indicating sign of Apoptosis. Further, molecular docking study in comparison to tamoxifen was also carried out to investigate the interaction of 8f with ER-α which favors its possible mode of Anticancer action.

Keywords

1,2,3-Triazole; Apoptosis; Breast cancer; Estrogen receptor; Molecular docking studies; Morphological alteration.

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