Author:

Keywords:

indoles, thiosemicarbazones, cytotoxicity, molecular modeling, sar, anticonvulsants, bioassays, maximal electroshock screen, semicarbazones, ketones, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Chemistry, Medicinal, Pharmacology & Pharmacy, Indoles, SAR, SEMICARBAZONES, KETONES, Animals, Anticonvulsants, Cell Line, Tumor, Cytotoxins, Drug Screening Assays, Antitumor, Female, Humans, Inhibitory Concentration 50, Leukemia L1210, Quantitative Structure-Activity Relationship, Rats, T-Lymphocytes, Thiosemicarbazones, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, Medicinal & Biomolecular Chemistry, 3404 Medicinal and biomolecular chemistry

Abstract:

Various substituted 1-arylmethyl-2,3-dioxo-2,3-dihydroindole thiosemicarbazones 3a-h, 1-benzyl-2,3-dioxo-2,3-dihydroindole N4-aryl thiosemicarbazones 4a-i and 1-benzyl-2,3-dioxy-2,3-dihydroindole N4-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 IC50 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.