Non steroidal anti-inflammatory drug (NSAIDs) in breast cancer chemotherapy; antimony(V) salicylate a DNA binder

Abstract

Abstract The organoantimony(V) derivative of salicylic acid (SalH2), {[Ph3Sb(SalH)]2O} (SalOSbi) was synthesized and tested for its anti-proliferative activity. SalOSbi was characterized by melting point and FT-IR, 1H NMR, Uv–Vis spectroscopic techniques. Its crystal and molecular structure is also determined by single-crystal X-ray diffraction crystallography. The antiproliferative activity of SalOSbi against human breast cancer cells: MCF-7 (Hormone Dependent (HD)) and MDA-MB-231 (Hormon Independent (HI) is congener or better than that of cisplatin. However SalOSbi is less toxic (by 7-fold) against human lung embryonic fibroblast cells (MRC-5), than cisplatin. Micronucleus assay shows that SalOSbi demonstrates similar in vitro genotoxicity with cisplatin against MRC-5 cells. The apoptotic type of cells death, caused by SalOSbi, was studied by cell cycle arrest and permeabilization of the mitochondrial membrane test. Electronic spectroscopic data confirm strong covalent binding of SalOSbi with DNA, through N(purine or pyrimidine)-M bonds in a similar manner to cisplatin. No inhibitory interaction with lipoxygenase (LOX) has been detected suggesting the non-involvement of the mitochondrial apoptotic pathway.