Microwave Assisted Synthesis, Biological Characterization and Docking Studies of Pyrimidine Derivatives

Author(s): Sanjay K. Rathwa, Manoj N. Bhoi, Mayuri A. Borad, Kinjal D. Patel, Dhanji P. Rajani, Smita D. Rajani, Hitesh D. Patel.

Journal Name: Current Microwave Chemistry

Volume 3 , Issue 3 , 2016

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Abstract:

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 Maestro 8.5).

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.

Keywords: Amino pyrimidine, anti-bacterial, anti-fungal, anti-malarial, docking, plasmodium falciparum, pyrimidine.

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2016
Page: [178 - 186]
Pages: 9
DOI: 10.2174/2213335602666150728205457
Price: $58

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