Synthesis and potential antimicrobial activity of novel α-aminophosphonates derivatives bearing substituted quinoline or quinolone and thiazole moieties

To develop novel antimicrobial agents, and based on the biologically active heterocyclic quinoline and thiazole substituted, a series of novel alpha-aminophosphonates (9a-h) and (10i-l) derivatives that incorporated quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were designed and synthesized via Kabachnik-Fields reaction in the presence of ionic liquid under ultrasound irradiation. All the new compounds were obtained in good yield with a simple workup and were confirmed using various spectroscopic methods. The in vitro antimicrobial activity of all synthesized compounds were screened in terms of MIC values against the selected strains of Gram-negative and Gram-positive bacteria and two fungal strains using the broth micro-dilution method. The results showed that most of the tested compounds showed moderate inhibitory activities against both Gram-positive and -negative bacteria compared with reference drugs. The following compounds 9e, 9g, 9h, 9i and 9f, 9g, 9h, 10k, 10l are the most active against Gram-positive and Gram-negative bacteria strains, respectively, with MIC values ranging between 0.25 and 128 mu g/mL. The synthesized compounds 9b, 9c, 9f, 9g, 9h, 10k, and 10l exhibited excellent antifungal inhibition with MIC values ranging between 0.25 and 32 mu g/mL. Structure-activity relationship revealed that the presence of coumarylthiazole moiety and hydroxyl in the quinoline group increased the inhibitory activity against microbial strains pathogens. These results confirm that the synthesized compounds can be potential antimicrobial drugs candidate.

Automated summary

Novel alpha-aminophosphonates derivatives incorporating quinoline or quinolone, and coumarylthiazole or 5-phenylthiazol-2-amine moieties were synthesized and screened for antimicrobial activity. The compounds showed moderate to strong inhibitory activities against Gram-positive and Gram-negative bacteria, with some exhibiting excellent antifungal inhibition. Structure-activity relationship analysis indicated that certain structural moieties enhanced the inhibitory activity against microbial pathogens, suggesting the synthesized compounds as potential antimicrobial drug candidates.