Design, Synthesis and In Vitro Anticancer Activity of a New Class of Bifunctional DNA Intercalators

Ana      Maria V. Zbancioc; Gheorghita      N. Zbancioc; Catalin      Tanase; Anca      Miron; Cornelia      Ursu; Ionel      I. Mangalagiu

Abstract

The emphasis of this work was to design and synthetize a new class of bifunctional DNA intercalators, containing in the same molecule an alkylating part and a nitrogen heterocycles intercalator unit. The adopted strategy is general, straightforward, and only involves two steps: acylation and quaternization. An alternative, fast, general, and environmentally friendly method for preparation of these compounds under microwave (MW) irradiation is also presented. The structure of compounds was proven by elemental (C, H, N) and spectral analysis (IR, 1H NMR, 13C NMR, COSY, HMQC, HMBC). The obtained compounds proved to have excellent anticancer activity in vitro. Possible mechanisms of action and structure-activity relationships are discussed.

Keywords: Bifunctional DNA intercalators, Diazine, 1,3-Diazols, Design, Synthesis, Microwave, Anticancer activity, Bifunctional DNA, Nitrogen heterocytes intercalator unit, Microway (M/W), Spectral analysis IR, Structure activity relationships, Cancer therapy, Chemotherapy, Cytotoxicity, Multidrug resistance, DNA-directed alkylating agents, DNA-affinic carriers, Shimadzu GCMS-QP2010, Chemical ionization (CI), CEM corporation, HeLa cell line, Cervicalendothelial carcinoma, DMEM medium, Student's “t” test, Nitrogen mustards, Halo-alkyl-ester chains, Enzyme inhibition, Diazine moieties, Imidazole, Carbamate prodrugs, Topoisomerase inhibitors, Microwave-assisted synthesis, Chromophore, Naphthyridine