Synthesis and biological evaluation of new sulfonamidoindoles

A new series of sulfonamidoindole derivatives which are expected to demonstrate antiviral, anticancer and antimycobacterial properties have been designed and synthesized. Thus 3-phenyl-5-sulfonamido-1H-indole-2-carbohydrazide (5) was treated with sodium nitrite and hydrochloric acid to yield 3-phenyl-5-sufonamido-1H-indole-2-carbonylazide (6). Refluxing 6 with absolute ethanol led to N-(3-phenyl-5-sufonamido-1H-indol-2-yl)carbamic acid ethyl ester (7). Hydrazinolysis of 7 gave 4-(3-phenyl-5-sufonamido-1H-indol-2-yl) semicarbazide (8) which was condensed with aromatic aldehydes to afford 4-(3-phenyl-5- sufonamido-1H-indol-2-yl)-1-(un)substituted benzylidenesemicarbazides (9). Compounds 9a-c, 9e, 9f and 9h were evaluated against some DNA and RNA viruses in CRFK, VERO, HEL and HeLa cell cultures. Most of the compounds showed varying degrees of inhibition below 50% cytotoxic concentration (CC50) or minumum cytotoxic concentration (MCC), but no specific antiviral effects (i.e. minimal antivirally effective concentration ≥5-fold lower than minimal cytotoxic concentration) were noted for any of the compounds against any of the viruses. 9e and 9f were selected for anticancer screening by the National Cancer Institute (NCI). 9e demonstrated the highest cytotoxicity against leukemia cell line SR (55.48%) and colon cancer cell line KM-12 (41.99%) in the primary screen. 9a-e, 9g and 9h were screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv using the microplate alamar blue assay (MABA), but none showed inhibition at 100 μg/ml.