1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549).

Autor: Khan A; Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India., Naaz F; Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India., Basit R; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India., Das D; Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India., Bisht P; Faculty of Life Sciences and Biology, South Asian University, New Delhi 110021, India., Shaikh M; Natural product and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India., Lone BA; Faculty of Life Sciences and Biology, South Asian University, New Delhi 110021, India., Pokharel YR; Faculty of Life Sciences and Biology, South Asian University, New Delhi 110021, India., Ahmed QN; Natural product and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India., Parveen S; Faculty of Science, Chemistry Department, Taibah University, Yanbu Branch, Yanbu 46423, Saudi Arabia., Ali I; Department of Microbiology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi 110062, India., Singh SK; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India., Chashoo G; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India., Shafi S; Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2022 Sep 01; Vol. 7 (36), pp. 32078-32100. Date of Electronic Publication: 2022 Sep 01 (Print Publication: 2022).
DOI: 10.1021/acsomega.2c03325
Abstrakt: A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin ( 10 ) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC 50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC 50 values of 6.65 and 5.55 μM, respectively, while compounds 18b , 18c , 18f , and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC 50 values ranging between 2.9 and 10.5 μM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC 50 value of 2.91 μM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds.
Competing Interests: The authors declare no competing financial interest.
(© 2022 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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