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ABSTRACT:
A new Mannich base of quinazolin-4-one derivatives possessing 1,3,4-oxadiazole ring have been synthesized by reacting 3-[4-(5-thioxo-4,5-dihydro-[1,3,4]oxadiazole-2-yl)-phenyl]-2-phenyl-3H-quinazolin-4-one (4) with different secondary amines and formaldehyde using N,N-dimethylformamide as the solvent to afford 3-[4-(4-substituted amino4-ylmethyl-5-thioxo-4,5-dihydro-[1,3,4]oxadiazole-2-yl)-phenyl]-2-phenyl-3H-quinazolin-4-ones (5a-e). The structures of the newly synthesized compounds have been established by analytical and spectral methods. The compounds have also been screened for their biological activity.
KEYWORDS: Synthesis, Oxadiazole, Antibacterial and antifungal activity
INTRODUCTION:
Quinazolinone derivatives possess potent biological activity such as analgesic, antibacterial, antifungal and antitumor. Several patent claims have been made on quinazolines as intermediates for potential antimalerials. 2,3-Disubstituted4-(3H)-quinazoline intermediates have been found to be active against Plasmodium galliaceum and showed antiinflammatory action on experimental edemas in animals1-5.
On the other hand 1,3,4-oxadiazoles are known to have broad spectrum of biological activities6-10. In the light of these interesting biological active evidences, we thought it worthwhile to synthesize some new quinazolinone derivatives containing oxadiazole moiety with the objective of screening them for their biological activity.
RESULTS AND DISCUSSION:
4-Amino benzoic acid was esterified using ethanol and catalytic amount of sulphuric acid to give 4-amino benzoic acid ethyl ester11. 2-Amino benzoic acid was allow to react with benzoyl chloride in pyridine to give 2-phenyl-3,1benzoxazin-4-one12(1) which on heating with 4-amino benzoic acid ethyl ester in pyridine yielded 4-(4-oxo-2phenyl-4H-quinazolin-3-yl)-benzoic acid ethyl ester (2).
The compound (2) was then condensed with hydrazine hydrate in ethanol to afford 4-(4-oxo-2-phenyl-4Hquinazolin-3-yl) benzoic acid hydrazide (3) in good yields which on treatment with ethanolic potassium hydroxide and carbon disulphide furnished 3-[4-(5-thioxo-4,5-dihydro[1,3,4]oxadiazole-2-yl)-phenyl]-2-phenyl-3H-quinazolin-4one (4). The reaction of the compound (4) with different secondary amines and formaldehyde using N,Ndimethylformamide afforded Mannich base 3-[4-(4substituted amine-4-ylmethyl-5-thioxo-4,5-dihydro-[1,3,4] oxadiazole-2-yl)-phenyl]-2-phenyl-3H-quinazolin-4ones (5a-d) [SCHEME 1].
BIOLOGICAL ACTIVITY:
Antibacterial Activity:
All the newly synthesized quinazolin-4-ones (5a-d) were screened in vitro for their antibacterial activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Salmonella typhosa by the ditch-plate technique13 using concentrations of 2 and 5 mg/ml. Nutrient agar was employed as culture media and DMF was used as solvent control for antibacterial activity.
The compound (5a) and (5b) showed moderate activity against Escherichia coli and Staphylococcus aureus. The compound (5d) exhibited high activity against Escherichia coli and moderate activity against Staphylococcus aureus. The compounds (5c) possessed weak activity against both Escherichia coli and Staphylococcus aureus.
Antifungal acitivity:
The compounds...