title: Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives.
abstract: Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from 1.46 × 10(4) to 6.01 × 10(4) M(-1). UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.
authors: Laboratório de Planejamento e Síntese de Fármacos, Departamento de Antibióticos, Universidade Federal de Pernambuco (UFPE), Recife 50670-901, PE, Brazil. maria.lima@pq.cnpq.br.
authors: Elizabeth Almeida
authors: EA
authors: Lafayette
authors: Sinara Mônica
authors: SM
authors: Vitalino de Almeida
authors: Marina Galdino da Rocha
authors: MG
authors: Pitta
authors: Eduardo Isidoro
authors: EI
authors: Carneiro Beltrão
authors: Teresinha Gonçalves
authors: TG
authors: da Silva
authors: Ricardo
authors: R
authors: Olímpio de Moura
authors: Ivan da Rocha
authors: Ida R
authors: Pitta
authors: Luiz Bezerra
authors: LB
authors: de Carvalho
authors: Maria do Carmo Alves
authors: Mdo C
authors: de Lima
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D004247:DNA; C427203:calf thymus DNA; D004264:DNA Topoisomerases, Type I