Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs with a potential for selective therapy of solid tumors by PMT and ADEPT strategies.
Pyrrolo[2,1-c][1,4]benzodiazepine-beta-glucuronide prodrugs 15a-b, with a potential for selective therapy of solid tumors by PMT and ADEPT have been designed, synthesized and evaluated for selective cytotoxicity in the presence of the enzyme beta-glucuronidase. The prodrugs have been found to possess reduced cytotoxicity compared to the parent moieties, and are excellent substrates for the enzyme, exhibiting cytotoxicity selectively in the presence of the enzyme. Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs.
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India. ahmedkamal@iict.res.in
Ahmed
A
Kamal
Venkatesh
V
Tekumalla
P
P
Raju
V G M
VG
Naidu
Prakash V
PV
Diwan
Ramakrishna
R
Sistla
D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000737:chemistry*; D006063:Chorionic Gonadotropin / Q000737:chemistry; D020719:Glucuronides / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry; D011623:gamma-Glutamyl Hydrolase / Q000737:chemistry
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D001570:Benzodiazepinones; D006063:Chorionic Gonadotropin; D020719:Glucuronides; D011355:Prodrugs; D014867:Water; D011623:gamma-Glutamyl Hydrolase