SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL 1,8-NAPHTHYRIDINES CONTAINING PYRAZOLINONE, PYRAZOLE, ISOXAZOLINONE, ISOXAZOLE AND PYRIMIDINE-2-ONESAbstract
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.
S. Raja *, K.N. Jayaveera , S. Subramanyam , A. Sunil Kumar Reddy and C. R. Prakash
Department of Pharmaceutical chemistry, GITAM Institute of Pharmacy, GITAM University, Vishakapatnam, Andhra Pradesh, India
21 January, 2016
26 February, 2016
17 March, 2016
01 June 2016