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Research Article

A Convenient and Practical Synthesis of Novel Pyrimidine Derivatives and its Therapeutic Potential

Author(s): Kaushal Arora, Amit Kumar and Prabhakar Kumar Verma*

Volume 20, Issue 10, 2024

Published on: 22 February, 2024

Article ID: e220224227309 Pages: 18

DOI: 10.2174/0115734072282575240213091008

Price: $65

Abstract

Background: A new series of 2-(2-(substituted aldehyde)hydrazinyl)-4-(2- chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile analogs (1–19) was prepared by using the Biginelli reaction.

Methods: TLC was employed to ensure the progress and confirmation of the reactions. Silica gel G was employed as the stationary phase, and mobile phases such as chloroform: toluene and acetone: n-hexane were used for the synthesized compounds. NMR.MS, IR, CHN spectral techniques used for the characterization of synthesized compound.

Results: The prepared derivatives were evaluated in vitro for antimicrobial activity against various bacteria and fungi using the tube dilution technique. Notably, compounds 2-(2-(3-Ethoxy-4- hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5- carbonitrile T1, 2-(2-(2-Hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6- dihydropyrimidine-5 carbonitrile T6, and 2-(2-(4-Hydroxybenzylidene)hydrazinyl)-4-(2- chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T16, displayed significant antibacterial activity, surpassing the standard drug Ampicillin. In the antifungal category, compounds 2-(2-(3-Ethoxy-4-hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyri midine-5-carbonitrile T1, 2-(2-(3,4-Dimethoxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6- oxo-1,6-dihydropyrimidine-5-carbonitrile T2, and 2-(2-(2,4-Dichlorobenzylidene)hydrazinyl)-4-(2- chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T13, were very much effective against both fungal strains A. niger as well as C. albicans. Furthermore, compounds 2-(2-(2- Hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5 carbonitrile T6, 2-(2-(2-Nitrobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyri midine-5-carbonitrile T8, 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo- 1,6-dihydropyrimidine-5-carbonitrile T12, and 2-(2-(4-Dimethylaminobenzylidene)hydrazinyl)-4-(2- chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T14 demonstrated remarkable antioxidant properties, because of their low IC50 values in the DPPH assay. In the realm of anticancer activity, 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydro pyrimidine-5-carbonitrile T9 outperformed the standard drug Adriamycin in terms of its effectiveness against human lung cancer cells (A-549) with a GI50 value of less than 10 according to the SRB assay. In addition, the antidiabetic assessment highlighted the excellent performance of compounds 2-(2- (2-Nitrobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5- carbonitrile T8, 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6- dihydropyrimidine-5-carbonitrile T12, and 2-(2-(3-Nitrobenzylidene)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T15, with low IC50 values, when tested for their inhibition of α-amylase enzyme activity.

Conclusions: The synthesized derivatives demonstrated strong antimicrobial, antioxidant, anticancer, and antidiabetic properties when assessed using specific methods and compared to established drugs. Notably, compounds 2-(2-(3-Ethoxy-4-hydroxybenzylidene)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T1, 2-(2-(2-Hydroxybenzylidene) hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5 carbonitrile T6, and 2- (2-(2,4-Dichlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine -5-carbonitrile T13, 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo- 1,6-dihydropyrimidine-5-carbonitrile T12 and 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile T9 exhibited even higher activity levels than the standard medications. The presence of electron-releasing groups in the synthesized compounds enhanced their antibacterial and antioxidant effects, particularly against B. subtilis. On the other hand, electron-withdrawing groups improved their anticancer and antidiabetic properties.

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