Diarilsulfetos análogos da combrestatatina A-4: avaliação toxicogenética, imunomodulatória, apoptótica e prospecção de um novo quimioterápico

Abstract

Combretastatin A-4 (CA-4) is an effective anticancer compound that is also able to overcome multidrug resistance, which have been promoting the development and research of CA-4 analogues. In this work, we determined the genotoxic, apoptotic and immunomodulatory activities of two CA-4 analogues based on diaril-sulfide in male Swiss mice. In addition, we also evaluated their activities when combined with cyclophosphamide, a DNA damaging agent commonly used in cancer therapy. The results showed that both compounds were able to induce DNA damage and apoptosis, but the analogue number 1 has a modest immunomodulatory activity, while the analogue number 2 increased splenic phagocytosis considerably. Furthermore, the analogue number 1 association with cyclophosphamide led a strong increase in both DNA damage and apoptosis, while the analogue number 2 combination with cyclophosphamide was slightly antagonist. These diverse activities indicate that, despite their structural similarity, the CA-4 analogues studied here can affect different molecular processes. In turn, this peculiarity suggests that distinct therapeutic applications can be prospect for these compounds.