RESUMEN
A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2'-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.
Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Anticarcinógenos/síntesis química , Anticarcinógenos/farmacología , Carbazoles/química , Chalconas/química , Administración Oral , Antiinfecciosos/química , Antiinfecciosos/farmacocinética , Anticarcinógenos/química , Anticarcinógenos/farmacocinética , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Línea Celular Tumoral , Técnicas de Química Sintética , Ensayos de Selección de Medicamentos Antitumorales , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacocinética , Depuradores de Radicales Libres/farmacología , Humanos , Relación Estructura-Actividad , Distribución TisularRESUMEN
Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activity. Most of the target compounds had more potent XO inhibitory activity than the standard drug (IC(50) = 4.3-5.6 µM). Interestingly, compound 7q bearing cyclopropyl ring was found to be the most potent inhibitor of XO (IC(50) = 4.3 µM). Molecular modelling study gave an insight into its binding modes with XO. Compounds 7a, 7d, 7e, 7g, and 7k were found to be potent inhibitors of tyrosinase (IC(50) = 14.01-17.52 µM). These results suggest the possible use of these compounds for the design and development of novel XO and tyrosinase inhibitors.