Synthesis, crystal structure, and ADME prediction studies of novel imidazopyrimidines as antibacterial and cytotoxic agents

Abstract

In the present study, a novel series of polyfunctionalized imidazopyrimidines 6a–u and 9a–d were efficiently constructed by a domino reaction between 2‐imino‐6‐substituted‐2,3‐dihydropyrimidin‐4(1H)‐ones 4a–d or 8a–c and 2‐bromoacetophenones 5a–i under mild basic conditions. The synthesized series were screened for their antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram‐positive (+) bacteria, as well as against Gram‐negative (−) bacteria Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhi. Most of the synthesized derivatives of imidazopyrimidines 6 and 9 showed remarkable selectivity against Gram(−) bacteria over the Gram(+) ones. Compounds 6c, 6f, and 6g displayed potent and broad‐spectrum antibacterial activity against all tested strains. Compounds 6f and 6g displayed promising inhibitory activity on GryB ATPase from E. coli with IC50 = 1.14 and 0.73 μM, respectively. Simultaneously, some of the synthesized imidazopyrimidines were screened for their antiproliferative activity against 60 cancer cell lines at a concentration of 10 μM. Compound 9d showed potent activity against most of the tested cell lines, with a mean growth inhibition of 37%. The ADME (absorption, distribution, metabolism, and excretion) prediction study demonstrated that the synthesized hits have, in addition to their promising chemotherapeutic activity, acceptable pharmacokinetic properties, and a drug‐likeness nature to be further developed.

Novel benzenesulfonamide‐thiouracil conjugates with a flexible N‐ethyl acetamide linker as selective CA IX and CA XII inhibitors

“…The starting 2-thioxo-5-cyanopyrimidinones 4a-h were initially prepared utilizing a one pot ternary reaction involving thiourea (1), ethyl cyanoacetate (2), and the aldehydes 3a-h under basic conditions. [32][33][34][35] Moreover, 6-substituted 2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 6a-e were synthesized by the reaction of thiourea (1) and β-keto esters 5a-e in the presence of KOH in ethanol. [36] Meanwhile, the intermediate 2chloro-N-(4-sulfamoylphenethyl)acetamide (9) was synthesized by the reaction of 4-(2-aminoethyl)benzenesulfonamide (7) with chloroacetyl chloride (8) in ice bath in DMF.…”

Effect of Sun Drying on Phytoconstituents and Antiviral Activity of Ginger against Low-Pathogenic Human Coronavirus

“…The bioavailability radar of the molecules obtained from Swiss ADME displayed some of the molecules exhibiting promising physicochemical properties for oral bioavailability. The ideal spaces of six physicochemical parameters-for example, polarity, size, solubility, lipophilicity, flexibility, and saturation for oral bioavailability of the representative molecules 1N5, 1N6, 1N8, and 1N9-are within the pink-colored area of Figure 1 [50,51]. If the radar plot of a molecule falls entirely in the pink area, it is considered drug-like.…”

Design and synthesis of novel lactam/thiazole derivatives having five membered thiazolyl ring and their antimicrobial activity

“…Thiazole derivatives have been discovered to be adaptable scaffolds with strong pharmacological properties that are frequently used in disease treatment. Thiazoles have different pharmacological properties against different diseased conditions [15][16][17][18][19][20]. These compounds also have an antifungal, antibacterial, antimalarial, antiproliferative, anti-inflammatory, antiviral, and antipyretic intermediate called Schiff base.…”