Synthesis and biological evaluation of new 5-methyl-N-(3-oxo-1-thia-4- azaspiro[4.5]-dec-4-yl)-3-phenyl-1H-indole-2-carboxamide derivatives

Abstract

A series of new 5-methyl-N-(3-oxo-1-thia-4-azaspiro[4.5]dec-4-yl)-3-phenyl- 1H-indole-2-carboxamide derivatives (2 and 3) was synthesized and characterized by IR, 1H-NMR, HSQC, HMBC, 13C-NMR (APT), APCI mass spectral data and elemental analysis. All synthesized compounds were evaluated for in vitro antituberculosis activity against M.tuberculosis H37Rv. Compound 3c was found to provide the highest (90%) inhibition of mycobacterial growth in the primary screen conducted at 6.25 μg/mL. Compounds 2a, 2b, 3a, 3b and 3c chosen as prototypes were evaluated against the full panel of 55 human tumour cell lines in the National Cancer Institute's in vitro primary cytotoxicity assay. 2b showed the most favourable cytotoxic effects on ovarium cancer cell line IGROV1 (log10 GI50 value -7.31) and renal cancer cell line UO-31 (log10 GI50 value -7.56), whereas 3a showed favorable cytotoxicity on renal cancer cell line RXF-393 (log10 GI50 value - 6.38). ©ARKAT.