2. Academic Validation
  3. Synthesis, computational studies and antiproliferative activities of coumarin-tagged 1,3,4-oxadiazole conjugates against MDA-MB-231 and MCF-7 human breast cancer cells

Synthesis, computational studies and antiproliferative activities of coumarin-tagged 1,3,4-oxadiazole conjugates against MDA-MB-231 and MCF-7 human breast cancer cells

  • Bioorg Med Chem. 2018 Nov 15;26(21):5612-5623. doi: 10.1016/j.bmc.2018.10.006.
Sanjeev Dhawan 1,  Nagaraju Kerru 1,  Paul Awolade 1,  Ashona Singh-Pillay 1,  Sourav Taru Saha 2,  Mandeep Kaur 2,  Sreekantha B Jonnalagadda 1,  Parvesh Singh 3
Affiliations

Affiliations

  • 1 School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000, South Africa.
  • 2 School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits, Johannesburg 2050, South Africa.
  • 3 School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000, South Africa. Electronic address: singhp4@ukzn.ac.za.
PMID: 30360952 DOI: 10.1016/j.bmc.2018.10.006
Abstract

A novel library of coumarin tagged 1,3,4 oxadiazole conjugates was synthesized and evaluated for their antiproliferative activities against MDA-MB-231 and MCF-7 breast Cancer cell lines. The evaluation studies revealed that compound 9d was the most potent molecule with an IC50 value of <5 µM against the MCF-7 cell line. Interestingly, compounds 10b and 11a showed a similar trend with lower inhibitory concentration (IC50 = 7.07 µM), in Estrogen Negative (ER-) cells than Estrogen Positive (ER+) cells. Structure-activity relationship (SAR) studies revealed that conjugates bearing benzyl moieties (9b, 9c and 9d) had superior activities compared to their alkyl analogues. The most potent compound 9d showed ∼1.4 times more potent activity than tamoxifen against MCF-7 cell line; while the introduction of sulfone unit in compounds 11a, 11b and 11c resulted in significant cytotoxicity against both MCF-7 and MDA-MB-231 cell lines. These results were further supported by docking studies, which revealed that the stronger binding affinity of the synthesized conjugates is due to the presence of sulfone unit attached to the substituted benzyl moiety in their pharmacophores.

Keywords

Coumarin; MCF-7; MDA-MB-231; Molecular hybridization; Oxadiazole; Triple-negative breast cancer (TNBC).

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