Química medicinal

Synthesis and Preliminary Antimicrobial Activity of New Schiff Bases of Pyrido [1,2-A] Pyrimidine Derivatives with Certain Amino Acids

Abstract

Shakir M Alwan, Jaafar Abdul-Sahib Al- Kaabi and Rafid MM Hashim

Pyrido [1,2-a] pyrimidine ring structure is one of the most interesting heterocycles in drug design and its derivatives have various potential pharmacological activities. An interesting approach of synthesizing a new series of pyridopyrimidine derivatives containing Schiff bases of certain amino acids, as privileged moieties of expected high potential in the field of antibacterial and antitumor agents, were investigated that may provide a synergistic model. The new derivatives 1-6 were synthesized by reacting 3-formyl-2H-pyrido [1, 2-a] pyrimidine-2, 4 (3H)-dione 1b with glycine, alanine, glutamic acid, histidine, tryptophan or leucine in methanol under reflux using glacial acetic acid as catalyst. The chemical structures of the new compounds and their intermediates (1-6, 1a and 1b) were characterized, identified and confirmed by spectral analysis (IR, 1H-NMR) and elemental microanalysis (CHN) and the results were within the acceptable limits. Disc-diffusion method was used to evaluate the antimicrobial activities of the newly synthesized compounds of interest 1-6, using Pseudomonas aurginosa, Staphylococcus aurueus, Bacillus subtilus, Candida albicans and Escherichia coli. The synthesized compounds 1-6 showed variable antibacterial activities ranged between good to moderately active, when compared with standards (amoxicillin and ceftriaxone). Compounds 4-6 also showed antifungal activities. However, compounds 5 and 6 are the most potent and have promising results. Compound 6 showed a good activity against all bacterial strains and fungi tested, while compound 5 showed the highest activity against Pseudomonas auroginosa. This approach has afforded the synthesis of new pyrido-pyrimidine derivatives containing Schiff bases of certain amino acids of reasonable and promising antibacterial activities.