Synthesis of novel indolyl-azetidinone and thiazolidinone derivatives as a potent antioxidant, antimicrobial and antitubercular agents

Abstract

The present study envisaged the development of novel antioxidant, antimicrobial and antimycobacterial candidates using the indole scaffold. Several novel indole derivatives, viz., 5-substituted 3-phenyl-N-[(2-phenyl-1H-indol-3-yl) methylene]-1H-indol-2-carboxamides(3a-c),1-(5-substituted-3-phenyl-1H-indol-2-carboxamidoyl)-2-oxo-3-chloro-4-(2-phenyl-1H-indol-3-yl)azetidines (4a-c) and 2-(2-phenyl-1H-indol-3-yl)-3-(5-substituted 3-phenyl-1H-indol-2-carboxamidoyl)-4-oxo-thiazolidines(5a-c) were prepared. The structures of these compounds were confirmed on the basis of their elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data. All these newly synthesized compounds were screened for their in-vitro antimicrobial activity by cup-plate method, anti-TB activity by alamar blue dye method, Antioxidant activities: like, 1,1-Diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity (RSA), Ferric ions (Fe3+) reducing antioxidant power (FRAP), Ferrous (Fe2+) metal ion chelating activity and invitro growth effect of tuberculosis activity using micro plate alamar blue dye assay (MABA). Compound 3a exhibited good (68.14%, IC50 value 50.67?g/ml) RSA at a concentration 100?g/ml, compound 3a higest bsorbance of FRAP 1.071nm at a concentration 100?g/ml, compound 3a showed good (57.96%, IC50 value <25?g/ml) chelating activity at a concentration 100?g/ml, compounds 3a, 4a and 5a showed highest growth inhibitory effect against all tested of bacteria E. coli, S. aureus, K. pneumonia and P. aeuroginosa. Compound 3a exhibited potent growth inhibitory effect against M. tuberculosis H37Rv (MIC= 0.2 ?g/mL). Screened in-vitro result of antioxidant, antimicrobial and antitubercular activities proved that the presence of electron-withdrawing group chlorine on the phenyl ring mostly favors the activity.