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

The 2-alkynylbenzothiazolium salts 3a-d incorporating an N-propargyl moiety have been prepared as aza-enediyne analogues. While these aza-enediynes ar e shown to be modest DNA cleavage agents, DNA cleavage was also observed wi th the N-methyl-2-alkynylbenzothiazolium salt 4, which lacks the aza-enediy ne moiety. The structural requirements for DNA cleavage, and the correlatio n of DNA cleavage efficiency with the propensity of these compounds to unde rgo nucleophilic addition by methanol support a proposed DNA cleavage mecha nism involving DNA alkylation. by appropriate 2-alkynyl-substituted benzoth iazolium salts. (C) 2001 Elsevier Science Ltd. All rights reserved.