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

Abstract

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. A novel series of 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile analogues (1–19) was synthesized using the Biginelli reaction 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 has characterized the synthesized compound. MS IR, CHN. 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. 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.