Nalidixic Acid Schiff Bases: Synthesis and Biological Evaluation

Background: The prevalence of morbidity and mortality due to infections from parasitic worms and protozoa is on rise especially in third world countries. The situation is further worsened by drug resistant microbial pathogens. Objectives: The antimicrobial and anthelmintic activities associated with substituted furfuraldehyde and 1,8-naphthyridine nucleus of nalidixic acid prompted us to synthesize some new quinolone Schiff bases with an aim to obtain potent antibacterial and anthelmintic agents with improved safety and efficacy. Methods: A new series of 1,8 naphthyridine based Schiff bases were designed and synthesized by the reaction of Nalidixic acid methyl ester 1 with hydrazine hydrate in anhydrous condition which yielded 1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carbohydrazide 2. The compound 2 was further treated with several furfural aldehydes to furnish the desired Schiff bases (3a-k). The in vitro antibacterial activity of Schiff bases was investigated against four Gram positive and four Gram negative bacterial strains. The newly prepared Schiff bases were also tested for their anthelmintic activity against Pheritima posthuma and Perionyx excavatus. Results: Chemical structures and identity of the prepared compounds were confirmed by their spectral data. Overall, Schiff bases (3a-k) showed good antimicrobial activity and interestingly five compounds exhibited more potent inhibitory effect than the standard drug Ampicillin against S. aureus, B. cereus, E. faecalis, S. epidermidis, E. coli, S. typhi and S. dysenteriae. Schiff bases also exhibited significant anthelmintic activity as indicated by their mean paralyses time (min) of 7.07-16.49, and 11.23-20.46 min against Perionyx excavatus and Pheritima posthuma in comparison to the 8.23 and 12.58 min shown by standard drug-Albendazole. Conclusion: It could be proposed that substitution of aromatic ring at C-5 of furfuryl heterocyclic ring in the Schiff bases produce compounds with promising antibacterial and anthelmintic actions.