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Novel Cyano- and Amidino- Benzothiazole Derivatives: Synthesis, Antitumor Evaluation, X-ray and QSAR Analysis

Synthesis of a series of novel cyano- and amidino- benzothiazole derivatives (3-31) is described. All studied amidino derivatives showed noticeable antiproliferative effect on several tumor cell lines. Cyano derivatives (11-17) showed considerably less pronounced activity due to their poor solubility in aqueous cell culture medium, which was confirmed by the principal components (PC) analysis. Compounds 21, 22, 28 and 29 were tested for their effects on the cell cycle and apoptosis, whereby 22 and 29, having methyl group at C-6 position in pyridine ring showed drastic cell cycle perturbations that were both concentration- and time-dependent and induced apoptosis. The QSAR modeling, based on the physico-chemical descriptors and on the measured biological activities, indicated the relevance of molecular polarizability and particular distribution of pharmacophores on molecular surface for the activity. In conclusion, benzothiazoles containing either isopropylamidino- or imidazolyl- groups will be considered as starting compounds for further investigation on lead identification

novel benzothiazoles ; synthesis ; amidines ; antitumor evaluation ; X-ray ; QSAR analysis

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