Design, Synthesis And Bioactivity Study Of Novel Naphthyl Thio-heterocyclic Compounds

DNA intercalators have found important uses in the study of interaction between DNA and small molecules and anticancer drug design. They generally consist of a flat, rigid and large conjugated aromatic structure. Also, artificial nucleases are of great interests from the standpoint of chemistry, biology and medicine.A series of angular thiazonaphthalimides was designed and synthesized by fusing a thiazole ring to the naphthalimide skeleton. The compound with the trifluoromethyl group had the highest DNA intercalating, photocleaving ability and antitumor activity against A549. The compound with the methyl group had the highest antitumor activity against P388.A series of linear and angular 2-aminothiazonaphthailimides was designed and synthesized by selectively fusing an aminothiazole ring to the naphthalimide skeleton. The linear compound was more active in bioactivities than its angular isomer.A series of linear substituted thiazonaphthailimides was modified from the 2-aminothiazonaphthalimide. All of them showed efficient antitumor activities against A549, P388 and HL-60 cell lines.A series of 2-substituted phenyl thiazonaphthalene carboxamides was designed and synthesized via decarbonylation reaction mediated by mercuric oxide. The compound having a methyloxide group intercalated into DNA most efficiently. The compound bearing an electron donating group photocleaved DNA more efficiently than its analogue bearing an electron withdrawn group.A series of 2-substituted phenyl thiazo- and thiadiazo- naphthalene carboxamides having aminoalkyl side chains at 5- or 6- position was designed and synthesized. The compound with the aminoalkyl side chain at 6-position was more active than its 5-position isomer in antitumor and DNA photocleaving activities.A series of benzothiopheno- and benzothixanthene- naphthalene carboxamides was designed and synthesized. The benzothiophenonaphthalene carboxamides intercalated into DNA more efficiently, but photocleaved DNA less efficiently than corresponding benzothixanthene isomers.All these naphthalimides and naphthalene carboxamides could hydrolyze different supercoiled plasmid DNA to fragments half size of the original plasmids without metal ions at 70 °C. The hydrolysis was time and concentration dependent. The naphthalimide could selectively hydrolyze DNA in G or C sequence.