Synthesis of Novel Quinolone and Coumarin Based 1,3,4-Thiadiazolyl and 1,3,4-Oxadiazolyl N-Mannich Bases as Potential Antimicrobials

Rahul      V. Patel; Jigar      K. Patel; Premlata      Kumari; Kishor      H. Chikhalia

Abstract

Two series of 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives have been synthesized and characterized by elemental and spectral (IR, 1H-NMR) data. The hydrazide derivatives of 4-hydroxy quinolone and coumarin moiety were refluxed in carbon disulfide in ethanolic potassium hydroxide to obtain the corresponding hydrazinecarbodithioate salts which were then treated in two ways with (i) sulfuric acid and (ii) hydrochloric acid at cooled temperature to furnish the corresponding 1,3,4-thiadiazole and 1,3,4-oxadiazole intermediates, respectively, which were then treated with piperazine bases in the presence of formalin in methanol to furnish the final N-Mannich products 7i-10vi. The newer analogs were examined for their antimicrobial activity against five bacteria (S. aureus and B. cereus, E. coli, P. aeruginosa and K. pneumoniae) and two fungi (A. niger and C. albicans) and the results revealed that compounds demonstrated excellent activity (MICs: 3.12-25 μg/mL) as compared with the standards (MICs: 6.25-25 μg/mL).

Keywords: 1, 3, 4-thiadiazole, 1, 3, 4-oxadiazole, antimicrobial activity, coumarin, piperazine, quinolone, anti-tuberculosis, anticancer, agents, sulphur