Thiazole Containing Nitrogen Mustards: Synthesis, Structural Evaluation, Cytotoxicity and DNA Binding Studies

Nulgulmnalli      Manjunathiah Raghavendra; Surampudi      Renuka; Sayan      Dutta Gupta; Pingili      Divya

Abstract

The present anticancer research demands more potent anticancer agents with fewer side effects than the existing ones. A series of novel substituted thiazole and benzothiazole containing nitrogen mustards (5-8; 15-17; 22-23) were synthesized and the structures of the compounds were analyzed by IR, NMR and mass spectras. Their in-vitro cytotoxicity against human lung carcinoma (A549) was investigated by MTT Assay. The compounds 16, 8 showed promising activity against A549 human lung carcinoma cell lines with % CPI 52 (More than Cisplatin) and 45.9 respectively. The DNA binding properties of the compounds were also evaluated based on their affinity or intercalation with CT-DNA measured with absorption titration. The compounds 22 and 5 showed the highest binding affinity with binding constant (Ki) 48.34 and 41.8 respectively.

Keywords: Anticancer activity, Benzothiazoles, Cytotoxicity, DNA binding, Nitrogen mustards, Thiazoles, recrystallized, diethanolamine, triethylamine, TLC plates, over anhydrous magnesium sulphate, scaffolds, aryl hydrocarbon receptor (AhR), TNF-a, 1H NMR