title: 1-Arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones as leads for developing cytotoxins and anticonvulsants.
abstract: Various substituted 1-arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones 3a-h, 1-benzyl-2,3-dioxo-2,3-dihydroindole N(4)-aryl thiosemicarbazones 4a-i and 1-benzyl-2,3-dioxy-2,3-dihydroindole N(4)-cyclohexylthiocarbazone 5 were synthesized. All of these compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Nearly 40% of these compounds possess low micromolar IC(50) values and some are either more potent than, or equipotent with, melphalan. Various correlations between the structures of these compounds and cytotoxic potencies were obtained which included the use of QSAR and molecular modeling techniques. Representative compounds displayed anticonvulsant properties in rats and were well tolerated by these animals. The encouraging biodata noted affords adequate rationale for outlining guidelines for further development of these molecular scaffolds.
authors.affiliation: Department of Pharmaceutical Chemistry, India. subhasskarki@hotmail.com
authors.forename: Subhas S
authors.initials: SS
authors.lastname: Karki
authors.forename: Vivek Singh
authors.initials: VS
authors.lastname: Bahaduria
authors.forename: Vivek
authors.initials: V
authors.lastname: Rana
authors.forename: Sujeet
authors.initials: S
authors.lastname: Kumar
authors.forename: Prasanna G
authors.initials: PG
authors.lastname: Subbaro
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D003603:Cytotoxins; D007211:Indoles; D013882:Thiosemicarbazones; C030374:indole