RESUMEN
Designed and synthesized were a series of 5H-chromeno[4,3-b]pyridines with substitution at 2- and 4-positions with various 5- or 6-membered heteroaromatics as antitumor agents. They were evaluated for topoisomerase I and II inhibitory activities as well as cytotoxicities against several human cancer cell lines. Structure-activity relationship study showed that 2-furyl or 2-thienyl at 2- or 4-position of central pyridine is crucial in displaying topo I or II inhibitory activity and cytotoxicity.
Asunto(s)
Antígenos de Neoplasias/metabolismo , Benzopiranos/síntesis química , Proliferación Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/metabolismo , ADN-Topoisomerasas de Tipo I/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias/enzimología , Piridinas/síntesis química , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa II/síntesis química , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Benzopiranos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Piridinas/farmacología , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa II/farmacologíaRESUMEN
Designed and synthesized 60 2-thienyl-4-furyl-6-aryl pyridine derivatives were evaluated for their topoisomerase I and II inhibitory activities at 20 microM and 100 microM and cytotoxicity against several human cancer cell lines. Compounds 8, 9, 11-29 showed significant topoisomerase II inhibitory activity and compounds 10 and 11 showed significant topoisomerase I inhibitory activity. Most of the compounds (7-21) possessing 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety showed higher or similar cytotoxicity against HCT15 cell line as compared to standards. Most of the selected compounds displayed moderate cytotoxicity against MCF-7, HeLa, DU145, and K562 cell lines. Structure-activity relationship study revealed that 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities.