Copper(II) chloride mediated synthesis and DNA photocleavage activity of 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines

A new class of photonucleases, 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines (4) was synthesized in a facile and efficient manner via copper(II) chloride mediated oxidative intramolecular cyclization of 2-(arylidenehydrazino)-3-substituted-quinoxalines (3). DNA cleavage potency of compounds 4a–d (40 μg each) was quantitatively evaluated on supercoiled plasmid ΦX174 under UV irradiation (312 nm, 15 W) without any additive. Compound 4c was found to be the most efficient DNA photocleaver which had converted supercoiled DNA (form I) into the relaxed DNA (form II) at 30 μg and the DNA photocleavage activity increases with increase in concentration of 4c.

Graphical abstract1-Aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines were synthesized and investigated as photoinducible DNA cleaving agents. Among these, compound 4c having 2′-thienyl moiety exhibited the most potent DNA cleavage activity against supercoiled ΦX174 plasmid.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► CuCl2 mediated efficient synthesis of fused triazoloquionoxalines. ► Photocleavage studies of compounds 4a–d on supercoiled ΦX174 DNA. ► Compound 4c photonicked DNA most efficiently from Form I into Form II. ► Photocleavage activity depends on the concentration and substituents at triazole ring.