2. Academic Validation
  3. New amide linked dimeric 1,2,3-triazoles bearing aryloxy scaffolds as a potent antiproliferative agents and EGFR tyrosine kinase phosphorylation inhibitors

New amide linked dimeric 1,2,3-triazoles bearing aryloxy scaffolds as a potent antiproliferative agents and EGFR tyrosine kinase phosphorylation inhibitors

  • Bioorg Med Chem Lett. 2019 Oct 1;29(19):126618. doi: 10.1016/j.bmcl.2019.08.022.
Tejshri R Deshmukh 1,  Aniket P Sarkate 2,  Deepak K Lokwani 3,  Shailee V Tiwari 4,  Rajaram Azad 5,  Bapurao B Shingate 6
Affiliations

Affiliations

  • 1 Department of Chemistry, Dr. Babasaheb Ambedkar, Marathwada University, Aurangabad 431 004, Maharashtra, India.
  • 2 Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, Maharashtra, India.
  • 3 Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education & Research, Shirpur 425 405, Maharashtra, India.
  • 4 Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani 431 401, Maharashtra, India.
  • 5 Department of Animal Biology, University of Hyderabad, Hyderabad 500 046, India.
  • 6 Department of Chemistry, Dr. Babasaheb Ambedkar, Marathwada University, Aurangabad 431 004, Maharashtra, India. Electronic address: bapushingate@gmail.com.
PMID: 31431361 DOI: 10.1016/j.bmcl.2019.08.022
Abstract

A search for potent antiproliferative agents has prompted to design and synthesize aryloxy bridged and amide linked dimeric 1,2,3-triazoles (7a-j) by using 1,3-dipolar cycloaddition reaction between 2-azido-N-phenylacetamides (4a-e) and bis(prop-2-yn-1-yloxy)benzenes (6a-b) via copper (I)-catalyzed Click Chemistry approach with good to excellent yields. All the newly synthesized compounds have been screened for their in vitro antiproliferative activities against two human Cancer cell lines. The compounds 7d, 7e, 7h, 7i and 7j have revealed promising antiproliferative activity against human breast Cancer cell line (MCF-7), whereas, the compounds 7a, 7b, 7c, 7i and 7j were observed as potent antiproliferative agents against human lung Cancer cell line (A-549). The active compounds against MCF-7 have been also analysed for their mechanism of action by the enzymatic study, which shows that the compounds 7d, 7h and 7j were acts as active EGFR tyrosine kinase phosphorylation inhibitors. In support to this biological study, the molecular docking as well as in silico ADME properties of all the newly synthesized hybrids were predicted.

Keywords

Antiproliferative activity; Click reaction; Dimeric 1,2,3-triazoles; EGFR tyrosine kinase phosphorylation inhibition; Molecular docking study.

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