DNA-binding agents

Synthesis and cytotoxicity studies of bifunctional hybrids of nitrogen mustards with potential enzymes inhibitors based on melamine framework

“…Thus, the diversity of action mode of triazine based inhibitors and presence of three reactive centres which could be used for the selective functionalization of the triazine scaffold have paved the way to a new class of hybrid anticancer drugs with a lowered toxicity and broader antitumour spectrum 24 . Therefore, while designing the structure of new hybrid anticancer drugs 25 we attempted to attach one, two, or three chloroethylamine groups to surround triazine substituted respectively with one (Scheme 1), two or three piperazine rings (Scheme 2). In order to prepare such constructs we made use of the observation 26,27 that some N-triazinylammonium chlorides 11a-f easy accessible from a broad range of triazines 9a-d and 1,4-diazabicyclo[2.2.2]octane (DABCO) (10) rearranged with a formation of 12a-f bearing 2-chloroethylamino fragment.…”

“…Therefore recent approaches involve development of hybrid cancer drugs 18 or application of 1,3,5-triazine as inductor of new specific molecular targets 19 . In these studies it has been attempted to introduce into 1,3,5-triazine scaffold one, two or three fragments bearing 2-chloroethylamine moiety characteristic for nitrogen mustards 20,21 and to confirm anti-proliferative activity of the obtained hybrids.…”