BACKGROUND: Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. METHODS: The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram +ve and Gram -ve strains were used to ascertain the spectrum of activity. ED50 values in the tail flick test were determined and recorded. Analgesic potential of compounds by using tail flick test in SWR male mice have also revealed promising results. RESULTS: All of the derivatives were effective in Gram -ve test against E. coli. None of the compounds show any inhibition of Gram +ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2,4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5≥6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed significant (P<0.01) antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. CONCLUSION: Comparing meta- and para- bromo substitutions, there had been significant (P<0.01) difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta- position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties.
BACKGROUND:Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. METHODS: The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram +ve and Gram -ve strains were used to ascertain the spectrum of activity. ED50 values in the tail flick test were determined and recorded. Analgesic potential of compounds by using tail flick test in SWR male mice have also revealed promising results. RESULTS: All of the derivatives were effective in Gram -ve test against E. coli. None of the compounds show any inhibition of Gram +ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2,4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5≥6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed significant (P<0.01) antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. CONCLUSION: Comparing meta- and para- bromo substitutions, there had been significant (P<0.01) difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta- position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties.
Authors: E Nicolaï; J Goyard; T Benchetrit; J M Teulon; F Caussade; A Virone; C Delchambre; A Cloarec Journal: J Med Chem Date: 1993-04-30 Impact factor: 7.446