DNA interaction of bromomethyl-substituted acridines

In this study, 1,8-bis(bromomethyl)acridine (2) and 2,7-bis(bromomethyl)acridine (3), monofunctional 2-(bromomethyl)-7-methylacridine (4) and 2,7-dimethylacridine (5) were synthesized, and their crosslinking and intercalative activities were investigated to assess the reactivity of bromomethyl acridines with DNA. Interstrand crosslinking activity was similar among the three bis(bromomethyl)acridines. The acridines exhibited intercalation activity for calf thymus DNA as follows:3 >  4 >  2 = 1 >>>  5. Intracellular DNA-crosslinking and DNA-intercalating activities were evaluated using the Ames assay.4 was mutagenic inSalmonella typhimurium TA100 and TA98, indicating that the bromomethyl group alkylated DNA bases. All three bis(bromomethyl)acridines were mutagenic inS. typhimurium TA92 and TA94, which can detect intracellular crosslinking DNA damage, whereas5 was not mutagenic in these strains. The results showed that the bis(bromomethyl)acridines crosslinked DNA and intercalated between DNA bases, and3 exhibited the highest crosslinking and intercalating activity.

Source: Medicinal Chemistry Research - November 7, 2017 Category: Chemistry Source Type: research