Synthesis and Cytotoxic Activity of Combretastatin A-4 and 2,3-Diphenyl-2-indazole Hybrids

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2021 Aug 28

PMID 34451912

Citations 4

Authors

Jaime Perez-Villanueva

Felix Matadamas-Martinez

Lilian Yepez-Mulia

Vadim Perez-Koldenkova

Martha Leyte-Lugo

Karen Rodriguez-Villar

Francisco Cortes-Benitez

Ana Perla Macias-Jimenez

Ignacio Gonzalez-Sanchez

Ariana Romero-Velasquez

Juan Francisco Palacios-Espinosa

Olivia Soria-Arteche

Affiliations

Soon will be listed here.

Abstract

Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2-indazole and 2,3-dipheny-2-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound , which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound .

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