RT info:eu-repo/semantics/article
T1 Expanding the Chemical Space of Withaferin A by Incorporating Silicon To Improve Its Clinical Potential on Human Ovarian Carcinoma Cells
A1 Perestelo, Nayra R.
A1 Llanos, Gabriel G.
A1 Reyes, Carolina P.
A1 Amesty, Ángel
A1 Sooda, Kartheek
A1 Afshinjavid, Saeed
A1 Jiménez Díaz, Ignacio Antonio
A1 Javid, Farideh
A1 López Bazzocchi, Isabel
AB Ovarian cancer represents the seventh mostcommonly diagnosed cancer worldwide. Herein, we report onthe development of a withaferin A (WA)-silyl ether librarywith 30 analogues reported for the first time. Cytotoxicityassays on human epithelial ovarian carcinoma cisplatinsensitiveand -resistant cell lines identified eight analoguesdisplaying nanomolar potency (IC50 ranging from 1 to 32nM), higher than that of the lead compound and referencedrug. This cytotoxic potency is also coupled with a goodselectivity index on a nontumoral cell line. Cell cycle analysisof two potent analogues revealed cell death by apoptosiswithout indication of cell cycle arrest in G0/G1 phase. Thestructure−activity relationship and in silico absorption, distribution, metabolism, and excretion studies demonstrated that theincorporation of silicon and a carbonyl group at C-4 in the WA framework enhances potency, selectivity, and drug likeness.These findings reveal analogues 22, 23, and 25 as potential candidates for clinical translation in patients with relapsed ovariancancer.
YR 2019
FD 2019
LK http://riull.ull.es/xmlui/handle/915/36066
UL http://riull.ull.es/xmlui/handle/915/36066
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 21-may-2024