SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL 1,8-NAPHTHYRIDINES CONTAINING PYRAZOLINONE, PYRAZOLE, ISOXAZOLINONE, ISOXAZOLE AND PYRIMIDINE-2-ONES

Diazonium salt of 2-(p-aminophenyl)-1,8-naphthyridine (I) was coupled with active methylene compounds  to afford the hydrazono-1,8-napthyridinyl (III-V) and azo(VI) derivatives. Hydrazono ethyl acetoacetate (III) and ethyl cyanoacetate (IV) derivatives on treatment with hydrazine and substituted hydrazine’s were later reacted with hydroxylamine HCl in the presence of ethanol followed by cyclization to afford pyrazolinone (IIIa-e) & (IVa-e) and isoxazolinones (VII&IX). Hydrazono acetyl acetone  (V) and azo dibenzoyl methane  (VI) derivatives on  treatment with hydrazine and substituted hydrazines, hydroxylamine HCl and with urea in the presence of ethanol  followed by  cylization  resulted in the formation of  pyrazoles (Va-e) & (VIa-e), isoxazole (IX&XI) and  substituted  pyrimidine-2-ones (X&XII). All the newly synthesized compounds were screened for their in-vitro antibacterial activity & antifungal activity   by Agar cup-plate method and Serial dilution methods. In Agar cup plate method the Compounds IIId, IVd, VId showed Impressive antibacterial and antifungal activity. In Serial dilution method the compounds Vd & VId showed excellent antibacterial activity against B.Subtilis with an MIC of 7.8 µg/ml where as the compounds IVd, Vd showed very good antifungal activity against A.niger and C.albicans with MIC value of 7.8 µg/ml & 15.6µg/ml. We found that  the  activity was due   to presence of chloro group at the para position of  phenyl ring of Pyrazolinone and pyrazole  and  also the presence of methyl group & amino group  at the 3rd position, hydrazono and azo (N=N)  group at 4th  of the pyrazolinone (IIId, IVd) and  pyrazole (Vd)  ring  are contributing to the antimicrobial activity.