Biological evaluation and synthesis of new pyrimidine-2(1H)-ol/-thiol derivatives derived from chalcones using the solid phase microwave method

Abstract

Twenty-five new hydroxy-and methoxy-substituted 4,6-diarylpyrimidin-2(1H)-ol (20-34) and 4,6-diarylpyrimidine-2(1H)-thiol derivatives (35-44) were synthesized from the reaction of the corresponding 1,3-diaryl-2-propene-1one compounds (1-19) with urea or thiourea using the solid-phase microwave method. All the new synthetic compounds (20-44) were evaluated with regard to their α-glucosidase activity. However, only compounds 22-25, 27, 31, 34, 35, 37, and 40 exhibited a greater inhibitory effect than standard acarbose. The IC 50 values of the active compounds ranged between 2.36 and 13.34 µ M. The 25 new compounds were also screened for their in vitro pancreatic lipase activity and compounds 20-27 and 35-39 were found to be active. Of these compounds 26, 27, and 39 exhibited the best antilipase activities at concentrations of 0.40 ± 0.06, 0.26 ± 0.07, and 0.29 ± 0.026 µ M. All the new compounds (20-44) were evaluated for their in vitro antimicrobial activity for nine test microorganisms. Compounds 20-24 and 35-39 were determined to possess a significant broad spectrum against the gram-positive bacteria Escherichia faecalis, Staphylococcus aureus, and Bacillus cereus among the tested bacterial agents. Compounds 20-24 and 35-39 exhibit the best activity against Mycobacterium smegmatis, with minimum inhibitory concentrations of 62.5-500 µ g/mL, indicating their potential use as antituberculous agents.

Biological Activity of Some Pyrimidine Derivatives: Cytotoxicity and Oxidative Stress Potential in Human Lung Cancer Cell line (A549).

“…Fandakli et al, (2016; 2018) used a solid-phase microwave method to synthesis 25 new hydroxy-and methoxy-substituent 4,6-diarylpyrimidine-2(1H)-ol and 4,6 diarylpyrimidine-2(1H)-thiol pyrimidine compound derivatives and evaluate their gram-negative and grampositive antibacterial activities, α-glucosidase activity and in vitro pancreatic lipase activity. Besides the antilipase activity and the inhibitory effects on αglucosidase, results showed that some of these original pyrimidine drivetives possess significant activity against Escherichia faecalis, Staphylococcus aureus, Bacillus cereus and Mycobacterium smegmatis with minimum inhibitory concentrations between 62.5 and 500 µg/mL [13,14].…”

“…The MDA and GSH levels and CAT activity were evaluated as endpoints of oxidative stress, one of the most important mechanisms of action of anticancer agents in cancerous cells. The tested pyrimidine derivatives ( Figure 1) were synthesized according to method of Fandakli et al [13,14]. Brifely, 15 mL of chloroform was used to dissolve urea (or thiourea), Methoxy-and hydroxysubstituted 1,3-diaryl-2-propene-1-one (4 mmol of each).…”

“…The anticancer activity of pyrimidine derivatives attracts the attention; especially that different pyrimidine nucleoside analogues as forodesin, tegafur, thioguanine, cytarabine, phasarabin and zebularine [12][13][14]; and DNA polymerase inhibitor as cytarabine are used in haematological malignancies and solid tumours treatment [12].…”

“…Inasmuch as different pyrimidine derivatives have anticancer activity and as antibiotics assume to be important group of antineoplastic agents; It was hypothesized that the previously synthesized [14] pyrimidine derivatives which have antibiotic activity have also anticancer activity. In order to test this hypothesis, the anticancer activity of the 6 pyrimidine derivatives with the highest antibacterial activity in the aforementioned study was evaluated in human lung cancer epithelial cell line (A549) one of the most widely used cell lines in toxicology and new drug development studies.…”

“…hexane and hexane diethyl ether solvent mixture and column chromatography was used to purify the chemicals. Methods and devices as nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), and liquid chromatography with tandem mass spectrometry (LC-MS/MS) were used to confirm the strctures [13,14].…”