Synthesis, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors.
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.
Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413255, Maharashtra, India. bandgar_bp@yahoo.com
Babasaheb P
BP
Bandgar
Laxman K
LK
Adsul
Hemant V
HV
Chavan
Sadanand N
SN
Shringare
Balaji L
BL
Korbad
Shivkumar S
SS
Jalde
Shrikant V
SV
Lonikar
Shivraj H
SH
Nile
Amol L
AL
Shirfule
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008543:Melanins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001549:Benzamides; D002227:Carbazoles; D004791:Enzyme Inhibitors; D008543:Melanins; C578007:N-(3-(3-(9-methyl-9H-carbazol-3-yl)-acryloyl)-phenyl)-benzamide; D014442:Monophenol Monooxygenase; D014969:Xanthine Oxidase