Promising Antidiabetic and Antimicrobial Agents Based on Fused Pyrimidine Derivatives: Molecular Modeling and Biological Evaluation with Histopathological Effect

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (8), p.2370
• Main Authors: Bassyouni, Fatma, Tarek, Mohammad, Salama, Abeer, Ibrahim, Bassant, Salah El Dine, Sawsan, Yassin, Nemat, Hassanein, Amina, Moharam, Maysa, Abdel-Rehim, Mohamed
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; antidiabetic activity; Antidiabetics; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antiinfectives and antibacterials; antimicrobial activity; Antimicrobial agents; Antioxidants; Bacillus cereus - drug effects; Carbohydrates; Cephradine; Cholesterol; Computer applications; Developing countries; Diabetes; Diabetes mellitus; Disease; Escherichia coli - drug effects; Evaluation; Fungi; Global health; Glucose; histopathological study; Histopathology; Hydrogen bonding; Hyperglycemia; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; In vivo methods and tests; Kidneys; LDCs; Liver; Metabolic disorders; Microbial Sensitivity Tests; molecular modeling; Molecular modelling; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Public health; pyrimidine derivatives; Pyrimidines - chemistry; Rhizomucor - drug effects; Salmonella; Staphylococcus aureus - drug effects; Structure-Activity Relationship
• ISSN: 1420-3049; 1431-5157; 1420-3049
• DOI: 10.3390/molecules26082370

Diabetes is the most common metabolic disorder in both developing and non-developing countries, and a well-recognized global health problem. The WHO anticipates an increase in cases from 171 million in 2000 to 366 million by 2030. In the present study, we focus on the preparation of pyrimidine derivatives as potential antidiabetic and antimicrobial agents. Thein vivoeffect on total serum glucose concentration, cholesterol and antioxidant activity was assessed in adult male albino Wister rats and compared to the reference drug glimperide. Promising results were observed for compound . The histopathological study confirms that compound results in significant activity with liver maintenance. The antimicrobial activities were evaluated against several bacterial strains such as ATCC 25566 NRRN 3008 ATCC 10145 ATCC 6538and fungi such as and Compounds and showed a good inhibition of the bacterial zone compared to the reference drug cephradine. Finally, we suggest protein targets for these drugs based on computational analysis, and infer their activities from their predicted modes of binding using molecular modeling. The molecular modeling for compounds and resulted in improved docking scores and hydrogen bonding. The docking studies are in good agreement with the in vitro and in vivo studies.