DEVELOPMENT OF SALINOMYCIN ANALOGS AS POTENTIAL ANTI-CANCER AGENTS

Salinomycin, a poly-ionophore antibiotic originally isolated from Streptomyces albus, exhibits antimicrobial activity against Gram-positive bacteria. Over the years Salinomycin has been studied in the effects it has on cancer, specifically cancer stem cells. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair. Inhibiting PARP has been explored as a strategy in cancer treatment, particularly in cancers with defective DNA repair mechanisms, such as those with BRCA mutations. The benzo-thiazoles, and -imidazoles are identified as inhibitor scaffolds, which compete with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. Benzothiazole, and benzimidazole based compounds particularly with modification at C2 position have shown significant PARP inhibitory action and selective cytotoxicity against breast cancer cell line (MCF-7). Based on the prior established anticancer activity of salinomycin, we undertook the synthesis of salinomycin conjugates at C1 carboxylic acid position by coupling with various substituted thiazoles, and imidazoles. The purity of the samples was established using 1H NMR and 13C NMR analysis and further quantified by LC-MS.