N-propargyl-2-alkynylbenzothiazolium aza-enediynes: role of the 2-alkynylbenzothiazolium functionality in DNA cleavage

Abstract

The 2-alkynylbenzothiazolium salts 3a–d incorporating an N-propargyl moiety have been prepared as aza-enediyne analogues. While these aza-enediynes are shown to be modest DNA cleavage agents, DNA cleavage was also observed with the N-methyl-2-alkynylbenzothiazolium salt 4, which lacks the aza-enediyne moiety. The structural requirements for DNA cleavage, and the correlation of DNA cleavage efficiency with the propensity of these compounds to undergo nucleophilic addition by methanol support a proposed DNA cleavage mechanism involving DNA alkylation by appropriate 2-alkynyl-substituted benzothiazolium salts. We have synthesized a series of 2-alkylnylbenzothiazolium salts, some of which possess an aza-enediyne moiety. These salts are modest DNA cleavage agents at pH 8 and 9; however, the DNA cleavage does not require the aza-enediyne functionality