A facile synthesis, characterization and biological evaluation of novel spiro-thiazolidinone and quinazolinone-thiazolidine derivatives

Abstract

The present work aims to synthesize and to perform antibacterial and antifungal screening of some novel spiro-thiazolidinone and quinazolinone-thiazolidine derivatives. The targeted derivatives have been synthesized in four steps. In the first step benzoyl chloride and anthranilic acid react together to form phenyl-4H-benzo[d][1,3]oxazin-4-one (1). Step 2 involves the reaction of 1 with thiourea and thiosemicarbazide to produce 4-oxo-2-phenylquinazoline-3(4H)-carbothioamide (2) and 1-(4-oxo-2-henylquinazolin-3(4H)-yl) thiourea (3) respectively. The reaction of synthesized compounds 2 and 3 with substituted isatin and substituted acetophenone yields imine derivatives 4a-c, 5a-c, 6a-c, and 7a-c respectively in the third step. The cyclization of imine derivatives with thioglycolic acid in the presence of zinc chloride yields the targeted spiro-thiazolidinone (8a-c, and 10a-c) and quinazolinone-thiazolidine (9a-c, and 11a-c) derivatives. Elemental analysis, FTIR, ¹H NMR, and mass spectral studies have been used for the characterization of the synthesized compounds. 8b (MIC 12.5 µg/mL) has been found to be the most effective derivative against B. subtilis. Compounds 9c and 11b, both with MICs of 12.5 µg/mL, are extremely effective against gram-negative bacterial strains of P. pneumonia, whereas compounds 9a and 11a have strong antibacterial activity against E. coli (MICs 12.5 µg/mL). With an average MIC value of 12.5 µg/mL in each case, compounds 8c, 9a, 10a, and 11a demonstrate good antifungal activity against A. niger, and C. albicans. The antifungal activity of compound 11b is highest against C. albican with MIC value of 6.25 µg/mL. The synthesized compounds exhibit strong antibacterial and antifungal activity against distinct pathogens.