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

Fatima Naaz; Faiz Ahmad; Bilal Ahmad Lone; Arif Khan; Kalicharan Sharma; IntzarAli; M ShaharYar; Yuba Raj Pokharel; Syed Shafi

doi:10.1021/acsmedchemlett.1c00304

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. eCollection 2021 Nov 11.

Authors

Fatima Naaz¹, Faiz Ahmad², Bilal Ahmad Lone², Arif Khan¹, Kalicharan Sharma³, IntzarAli⁴, M ShaharYar³, Yuba Raj Pokharel², Syed Shafi¹

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 protein.