Apoptosis Inducing 1,3,4-Oxadiazole Conjugates of Capsaicin: Their In Vitro Antiproliferative and In Silico Studies.
Fatima NaazFaiz AhmadBilal Ahmad LoneArif KhanKalicharan Sharmanull IntzarAliM ShaharYarYuba Raj PokharelSyed ShafiPublished in: ACS medicinal chemistry letters (2021)
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.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- endothelial cells
- oxidative stress
- dna damage
- cell cycle arrest
- molecular docking
- cell death
- vascular endothelial growth factor
- pi k akt
- case control
- papillary thyroid
- poor prognosis
- binding protein
- single cell
- cell proliferation
- dna repair
- cell therapy
- cancer therapy
- squamous cell carcinoma
- stem cells
- small molecule
- squamous cell
- anti inflammatory
- protein protein
- young adults
- childhood cancer
- pluripotent stem cells