Synthesis, DNA binding, and Leishmania topoisomerase inhibition activities of a novel series of anthra[1,2-d]imidazole-6,11-dione derivatives.
Nine novel anthra[1,2-d]imidazole-6,11-diones, differing in their side chain, were synthesized. UV-vis spectroscopy and viscometric titrations of these molecules with duplex DNA were used to assess their binding with DNA. Five of the nine compounds showed high inhibition activity against topoisomerase I of Leishmania donovani, with the one bearing the tetrazole side chain exhibiting an IC50 approximately 1 microM. The inhibition activities were not related with their DNA binding affinity and depended on the nature of the side chain.
Chaudhuri
Padmaparna
P
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India.
Majumder
Hemanta K
HK
Bhattacharya
Santanu
S
D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry; D002166:Camptothecin / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007893:Leishmania donovani / Q000201:enzymology*; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry
D000873:Anthracenes; D007093:Imidazoles; D009025:Morpholines; D059004:Topoisomerase I Inhibitors; D014344:Trypanocidal Agents; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin