Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines.

Luis Sánchez-Sánchez,Edgar Zenteno,Gabriel Guerrero-Luna,María Fernández-Herrera,Alan Carrasco-Carballo,Jesús Sandoval-Ramírez,María Hernández-Linares,Hugo López-Muñoz,María Escobar

doi:10.3390/molecules21111533

Abstract

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells. These derivatives were synthesized from the steroidal sapogenin diosgenin in good yields. The in vitro assays show that the steroidal oximes show significant antiproliferative activity compared to the one observed for diosgenin. Cell proliferation, cell death, and the cytotoxic effects were determined in both cervical cancer cells and human lymphocytes. The cancer cells showed apoptotic morphology and an increased presence of active caspase-3, providing the notion of a death pathway in the cell. Significantly, the steroidal oximes did not exert a cytotoxic effect on lymphocytes.

Highlights

Cancers figure among the leading causes of morbidity and mortality worldwide, with therapies based primarily on surgery, radiation therapy, and chemotherapy which, to date, are not successful interventions, and the complete removal of the cancer without damage to other tissues is the ideal goal of treatment
We evaluated the antiproliferative activity of steroidal oxime derivatives; it is not the aim of this study to describe aspects of the molecular mechanisms that regulate the observed antitumor effects
The assays showed that the steroidal oximes 4 and 5 generate interesting results in the antiproliferative activity in vitro compared to the activity observed with diosgenin (1)

Summary

Introduction

Cancers figure among the leading causes of morbidity and mortality worldwide, with therapies based primarily on surgery, radiation therapy, and chemotherapy which, to date, are not successful interventions, and the complete removal of the cancer without damage to other tissues is the ideal goal of treatment Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissues or to spread to distant sites by microscopic metastasis often limits its effectiveness. Antitumor research is a very active field, and a large amount of information dealing with clinical aspects of cancer chemotherapy is generated; there is, a continuing need for Molecules 2016, 21, 1533; doi:10.3390/molecules21111533 www.mdpi.com/journal/molecules new treatments inspired by medicinal chemistry and drug design. Synthetic chemistry has been find a solution to to themodify problem of targets, the limited supply of natural products byorder developing broadly employed drug especially those of natural origin, in to find asynthetic solution strategies

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