Synthesis, antimicrobial, antimycobacterial and structure–activity relationship of substituted pyrazolo-, isoxazolo-, pyrimido- and mercaptopyrimidocyclohepta[b]indoles

A new class of heterocycles, specifically substituted pyrazolo-, isoxazolo- and pyrimidocyclohepta[b]indoles, has been prepared by condensation of substituted 7-(hydroxymethylene)-7,8,9,10-tetrahydrocyclohepta[b]indol-6(5H)-ones with hydrazine hydrate, hydroxylamine hydrochloride, phenylhydrazine, urea and thiourea, respectively. The structures of the compounds were established by IR, 1H NMR, 13C NMR, mass spectral analysis, X-ray diffraction, and the compounds have been screened for in vitro antimicrobial and antimycobacterial against Mycobacterium tuberculosis H37Rv (MTB). Among the compounds screened, five substances were found to have an MIC of 3.12 μg/ml or greater against MTB. Structure–activity relationship (SAR) analyses and in silico drug relevant properties (HBD, HBA, PSA, c Log P, M.wt) confirmed that the compounds are potential lead compounds for future drug discovery studies.

The hererofused cyclohepta[b]indoles were synthesized and subjected to in vitro antimicrobial and antimycobacterial activities.Figure optionsDownload as PowerPoint slideHighlights
► Synthesis and characterization of novel substituted pyrazolo-, isoxazolo-, pyrimido- and mercaptopyrimidocyclohepta[b]indoles.
► Pyrazole, isoxazole, pyrimidine units display a pronounced activity against antimicrobial activity.
► 3e, 4e, 5e and 6e were found to be the most active with MIC of 3.12 μg/mL against Mycobacterium tuberculosis H37Rv.
► The structure–activity relationship (SAR) and in silico drug relevant properties.