Background: Microwave-assisted organic synthesis has rapidly evolved in the last decade
as a well-organized utensil for synthetic chemists. The pyrimidine scaffold still residues as one of the
most valuable class of compounds for the synthesis of clinically useful drugs. Molecular docking is
frequently used to forecast the binding orientation. The probability of binding of protein to pyrimidine
analogues is fascinating and Docking is used to bring out new ligands for biological targets with a
known 3D structure.
Methods: Pyrimidine derivatives 5a-5i was synthesized from Chalcones through condensation reaction
with guanidine hydrochloride in presence of basic medium via both conventional and Microwave assisted method.
In vitro anti-malarial activity against P. falciparum strain, the synthesized compounds were also screened for antibacterial
activities against Gram-positive bacteria and Gram-negative bacteria, then done antifungal activity. Molecular modeling
study of synthesized compounds as well as the marketed drug pyrimethamine was performed by Glide 5.0 (Schrodinger
Results: Microwave assisted is a very good method for the synthesis of pyrimidine derivatives, in reverence to less time
and giving excellent yields as compare to the conventional method. Our results indicated that analogue 5g and 5i show the
most pronounced excellent anti-malarial activity, IC50 Value 0.55, 0.70 (μg/mL) respectively. On the other hand Compound
5a, 5d, 5f, 5g, 5h and 5i possesses good activity against Gram negative and Gram positive bacteria. And compound
5c, 5e and 5f shown excellent antifungal activity.
Conclusion: We conclude microwave assisted synthesis is an excellent method as camper to conventional heating. The
experimental activity profiles were furthermore validated by docking studies thru the inhibition of P. falciparum dihydrofolate
reductase (PfDHFR), a probable target for the improvement of new anti-malarial agents.