ABSTRACT
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 300 mg/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".
Subject(s)
Breast Neoplasms/pathology , Steroids/chemistry , Stilbenes/chemical synthesis , Stilbenes/pharmacology , Animals , Cell Line, Tumor , Female , Humans , Magnetic Resonance Spectroscopy , Mice , Rats , Rats, Sprague-Dawley , Spectrometry, Mass, Electrospray Ionization , Stilbenes/chemistryABSTRACT
Phenstatin analogues were synthesized on steroidal framework, for selective targeting of breast cancer cells. These analogues were evaluated for anticancer efficacy against breast cancer cell lines. Analogues 12 and 19 exhibited significant anticancer activity against MCF-7, hormone dependent breast cancer cell line. While analogues 10-14 exhibited significant anticancer activity against MDA-MB-231, hormone independent breast cancer cell line. Compound 10 showed significant oestrogen antagonistic activities with low agonistic activity in in vivo rat model. These analogues also retain tubulin polymerization inhibition activity. The most active analogue 10 was found to be non-toxic in Swiss albino mice up to 300 mg/kg dose. Gallic acid based phenstatin analogues may further be optimized as selective anti-breast cancer agents.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Gallic Acid/chemistry , Polymerization/drug effects , Tubulin/metabolism , Animals , Cell Line, Tumor , Female , Humans , Rats , Rats, Sprague-DawleyABSTRACT
Phytol, a diterpene alcohol was modified to several semisynthetic analogues. Some of the modifications were done logically to enhance lipophilicity of the molecule. Analogues 14, 16 and 18 exhibited antitubercular activity (MIC 15.6-50microg/mL) better than phytol (100microg/mL). The most potent analogue 18 was evaluated for in vivo toxicity in Swiss albino mice and was well tolerated by the experimental animals up to 300mg/kg body weight as a single oral acute dose.
