1-Arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones as leads for developing cytotoxins and anticonvulsants.
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.
Karki
Subhas S
SS
Department of Pharmaceutical Chemistry, India. subhasskarki@hotmail.com
Bahaduria
Vivek Singh
VS
Rana
Vivek
V
Kumar
Sujeet
S
Subbaro
Prasanna G
PG
Das
Umashankar
U
Balzarini
Jan
J
De Clercq
Erik
E
Dimmock
Jonathan R
JR
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
D000927:Anticonvulsants; D003603:Cytotoxins; D007211:Indoles; D013882:Thiosemicarbazones; C030374:indole