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 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.

Keywords::

• Indoles
• thiosemicarbazones
• cytotoxicity
• molecular modeling
• SAR
• anticonvulsants
• bioassays

Acknowledgements

The authors thank Professor B. G. Desai of the KLES College of Pharmacy, Bangalore, India for providing the necessary facilities. The Government of India, Ministry of Science and Technology, awarded a BOYSCAST Fellowship to Dr. S. S. Karki which enabled him to work at the University of Saskatchewan as a Visiting Scholar which is gratefully acknowledged. Appreciation is extended to the Belgian Fonds voor Wetenschappelijk Onderzoek (Vlaanderen) which funded the cytotoxicity assays and to Mrs. L. van Berckelaer for excellent technical assistance. Ms. B. McCullough is thanked for typing the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.