Microwave Assisted, Antimicrobial Activity and Molecular Modeling of Some Synthesized Newly Pyrimidine Derivatives Using 1, 4-diazabicyclo[2.2.2]octane as a Catalyst

Background: Pyrimidine ring is one of the most important heterocyclic scaffolds due to its biological benefits as antimicrobial agents via acting as competitive suppressors of dihydropteroate synthase (DHPS) enzyme, inhibiting dihydrofolate reductase or glucosamine N-phosphate synthase. Objective: The objective of this work is preparing twenty four derivatives of pyrimidine heterocycle 1a-f, 2a-f, 3a-f and 4a-f via a facile one step reaction with antimicrobial potential. Methods: Novel twenty four derivatives of pyrimidine heterocycle 1a-f, 2a-f, 3a-f and 4a-f were prepared via a facile one step reaction by treating substituted aldehydes, urea and / or thiourea and active methylene derivatives (diethyl malonate and / or ethyl cyanoacetate) using 1,4- diazabicyclo[2.2.2]octane (DABCO) as a basic catalyst. The chemical structures of all these novel targets were proved by 1HNMR, 13CNMR, MS and elemental analyses. All the twenty four new targets 1a-f, 2a-f, 3a-f and 4a-f were assessed for their antimicrobial activity towards bacteria as Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli and against fungi represented by Aspergillus flavus and Candida albicans. Results: Most of the compounds exhibited very good antimicrobial activity, especially; compound (1c) exhibited the most activity against three types of bacteria Escherichia coli, Bacillus subtilis, Staphylococcus aureus. Moreover, this derivative 1c displayed similar antifungal activity towards Candida albicans as that exhibited by amphotericin B. Conclusion: All the screened compounds 1a-f, 2a-f, 3a-f and 4a-f showed antibacterial activity with inhibition zone diameter range 6-21 mm/mg, while, regarding the antifungal activity, all the novel derivatives except 2b, 2d, 3a, 3c, 3e did not have any effect towards Aspergillus flavus and 3d did not reveal any inhibitory activity towards both fungal species.