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  2. Apoptosis Inducing 1,3,4-Oxadiazole Conjugates of Capsaicin: Their In Vitro Antiproliferative and In Silico Studies

Apoptosis Inducing 1,3,4-Oxadiazole Conjugates of Capsaicin: Their In Vitro Antiproliferative and In Silico Studies

  • ACS Med Chem Lett. 2021 Oct 21;12(11):1694-1702. doi: 10.1021/acsmedchemlett.1c00304.
Fatima Naaz 1 Faiz Ahmad 2 Bilal Ahmad Lone 2 Arif Khan 1 Kalicharan Sharma 3 IntzarAli 4 M ShaharYar 3 Yuba Raj Pokharel 2 Syed Shafi 1
Affiliations

Affiliations

  • 1 Department of Chemistry, School of Chemical and Lifescience, Jamia Hamdard, New Delhi-110062, India.
  • 2 Faculty of Life Sciences and Biology, South Asian University, New Delhi-110021, India.
  • 3 Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi-110062, India.
  • 4 Department of Medical Microbiology, Hamdard Institute of Medical Studies and Research, Jamia Hamdard, New Delhi-110062, India.
Abstract

A series of 1,3,4-oxadiazole tethered capsaicin derivatives was prepared by using one point modification at the vanillyl-hydroxyl group of capsaicin. All the prepared capsaicinoids were evaluated for their antiproliferative activity against NCI-60 human Cancer cell lines at 10 μM. Among the compounds tested, compound 20a exhibited good cytotoxic activity against HCT-116, NCI-H460, and SKOV3 cell lines with IC50 8.55 μΜ, 5.41 μΜ, and 6.4 μΜ, respectively, compared to the parent natural product capsaicin. Further on, it significantly inhibited the colony formation in NCI-H460 in a dose dependent manner and enhanced the ROS effect. It also caused cell arrest at the S phase and induced Apoptosis via suppressing the Pro PARP marker. Compound 20a exhibited an antimigratory property and suppressed the expression of the VEGF marker in a dose dependent manner. Furthermore, compound 20a also suppressed the effects of the p-Erk, p-p38, and P-CNA makers. In silico studies supported the interaction of this class of compounds with the VEGFR2/KDR/Flk-1 protein.

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