Novel structural hybrids of quinoline and thiazole moieties: Synthesis and evaluation of antibacterial and antifungal activities with molecular modeling studies

Abstract

One of the best ways to design new biocidal agents is synthesizing hybrid molecules by combining two or more bioactive moieties in a single molecular scaffold. So, new series of quinolines bearing a thiazole moiety were synthesized using thiosemicarbazones 2a-f. Cyclization of 2a-f with ethyl chloroacetate, ethyl 2-chloropropanoate or chloroacetone afforded the corresponding thiazoles 3-5. The antimicrobial activity of the new quinoline derivatives was evaluated. The most of tested compounds revealed potent both of the antibacterial and antifungal activities. Fourfold potency of amphotericin B for the inhibition the growth of the A. fumigatus was displayed by ccompound 5e. The latter compound displayed twofold potency of gentamycin for inhibition the growth of N. gonorrhoeae. Moreover, this compound showed equipotent potency of references drugs for inhibition of the growth of S. flexneri, S. pyogenes, P. vulgaris, A. clavatus, G. candidum and P. marneffei. So, quinolines bearing a thiazole moiety can be suggested as interesting scaffolds for the development both of the novel antibacterial and antifungal agents. Some new derivatives were studied as peptide deformylase enzyme inhibitors. Thiazolidin-4-one derivative 3d and 2,3-dihydrothiazole derivative 5c had shown good PDF inhibition activity, which had been supported by the docking results with highest binding affinity and lowest docking energy score. These results suggested that the most potent compounds might be possible agents as novel bacterial PDF inhibitor.

Keywords: ADME prediction; Antibacterial and antifungal activities; Molecular docking; PDF inhibitor; Quinolines; Thiazoles; Thiosemicarbazones.