Synthesis of new 1,2,4-Triazole derivatives of nalidixic acid as potential antibacterial and antifungal agents

ABSTRACT

Triazole and triazole fused heterocyclic ring systems possess diverse applications in the fields of medicine, agriculture and industry. A new series of nalidixic acid derivatives having 1,2,4-triazole moiety at position 3 were synthesised to achieve enhanced biological activity and wide spectrum of activity. Nalidixic acid was first converted into its methyl ester which upon hydrazinolysis afforded nalidixic acid hydrazide. Condensation of the hydrazide with CS[2]/KOH furnished the potassium dithiocarbazate salt, which cyclized to the 3-[4-amino-5-thioxo-4,5-dihydro-1H-l,2,4-triazol-3-yl]-1-ethyl-7-methyl-1H-[1,8] naphthyridin-4-one, [4], on refluxing with hydrazine hydrate. Condensation of the key intermediate 4 with aryl aldehydes afforded Schiffs bases 5a-f, while its reaction with alkyl or aralkyl halides gave compounds 6a-e. Furthermore, compounds 5a,e were reacted with benzyl chloride to afford 7a,b. The chemical structure of the target compounds was confirmed by IR, [1]H-NMR, FAB-MS, EI-MS spectra and elemental analyses. The title compounds and the starting Nalidixic acid; were tested for their in-vitro antibacterial and antifungal activities. Most of the tested compounds showed comparable antibacterial activity with those of Nalidixic acid and higher activity than ampicillin. The tested compounds and Nalidixic acid showed non or moderate antifungal activity in comparison to clotrimazole as a reference drug