((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2-yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar cycloaddition methodology, as DNA intercalating agents and evaluated for their anticancer activity against human cervical carcinoma HeLa and head and neck squamous cells carcinoma cell lines. The synthesized compounds exhibited good cytotoxic activity with IC50better than cisplatin, used as the main and effective treatment for HNSCC, and a 24.3â 72.0-fold selectivity respect to the 184B5 non-cancerous immortalized breast epithelial cell lines. Unwinding assay, circular dichroism data, and Uv-vis melting experiments confirmed that these compounds act as DNA intercalators with a binding constant in the order of 104Mâ 1. Docking studies showed that both compounds can interact as intercalating agent with both poly-d(AT)2and poly-d(GC)2, preferring an entrance by the minor groove of the poly-d(AT)2.

DNA intercalators based on (1,10-phenanthrolin-2-yl)isoxazolidin-5-yl core with better growth inhibition and selectivity than cisplatin upon head and neck squamous cells carcinoma

Zagni Chiara;Mineo Placido;Floresta Giuseppe;Monciino Giulia;Pistara Venerando;Abbadessa Antonio;Nicosia Angelo;Amata Emanuele;Rescifina Antonio
2018-01-01

Abstract

((3RS,5SR)- and ((3RS,5RS)-2-(2-methoxybenzyl)-3-(1,10-phenanthrolin-2-yl)isoxazolidin-5-yl)methanol have been synthesized, according to 1,3-dipolar cycloaddition methodology, as DNA intercalating agents and evaluated for their anticancer activity against human cervical carcinoma HeLa and head and neck squamous cells carcinoma cell lines. The synthesized compounds exhibited good cytotoxic activity with IC50better than cisplatin, used as the main and effective treatment for HNSCC, and a 24.3â 72.0-fold selectivity respect to the 184B5 non-cancerous immortalized breast epithelial cell lines. Unwinding assay, circular dichroism data, and Uv-vis melting experiments confirmed that these compounds act as DNA intercalators with a binding constant in the order of 104Mâ 1. Docking studies showed that both compounds can interact as intercalating agent with both poly-d(AT)2and poly-d(GC)2, preferring an entrance by the minor groove of the poly-d(AT)2.
2018
1,3-Dipolar cycloaddition; DNA-intercalators; Head and neck squamous cells carcinoma; HeLa; Isoxazolidines; Pharmacology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/314984
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