Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity

Combretastatin A4 analogues have been synthesized on steroidal framework. Analogue 22 exhibited potent anti-breast cancer activity through strong tubulin polymerisation inhibition activity and was found to be non-toxic in Swiss albino mice. [Display omitted] ▶ Combretastatin A4 analogues on steroidal framework exhibited potent anti-breast cancer activity. ▶ Compound 22, potent cytotoxicity against both ER positive (MCF-7; IC50=7.5μM) & ER negative (MDA-MB-231; IC50=5.5μM) and antitubulin activity (IC50=0.96μM). ▶ Compound 22, in vivo toxicity-safe up to 300mg/kg dose. Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 & MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled “Synthesis and biological testing of steroid derivatives as inhibitors”.