Synthesis and Exploration of Thiadiazolinone-linked Quinazolidinone Derivatives

Background: Infections caused by various microbes is one of the important threats for mankind because of their ability of surviving and proliferating in a radically changing environment. The development of resistance to the existing drug regimen has made the situation even more threatening. This condition has left us with the option to design new chemical entities with more potency and low probability to develop resistance. Methods: In view of developing more potent antimicrobials, a novel series of thiazolidinone linked quinazolidinones (6a-e) were synthesized from 2-phenyl-4H- 3,1-benzoxazin-4-ones as the starting compound. The starting compound was converted into (2-phenyl-3,4-dihydro-4- oxo-quinazolin-3yl) acetic acid by condensation with glycine. The resulting compound was converted into corresponding ester and hydrazide. The schiffs bases of the compound were made by condensation with various aromatic aldehydes. The title compounds (6a-e) were prepared by the cyclization with thiolactic acid. All the derivatives were evaluated for their antibacterial and antifungal potential. Results: The structures were confirmed through spectral and elemental analysis and the designed entities were obtained in good yield. Most of the derivatives were showing significant antibacterial and antifungal activity warranting the discovery a novel series of antimicrobials. Conclusion: Since the novel series of quinazolinones with thiazolidinone linked through amide moiety having an electron withdrawing group, had exhibited significant antimicrobial activity profile, more exploration of this scaffold attached with different electron withdrawing groups can be considered as a potential lead for novel antimicrobial research. Keywords: Antibacterial activity, antifungal activity, quinazolidinone, schiff’s base, thiazolidinone.