Diastereoselective synthesis, characterization, investigation of anticancer, antibacterial activities, in silico approaches and DNA/BSA binding affinities of novel pyrimidine-sugar derivatives

Abstract

Eighteen novel carbohydrate conjugates (1-9) and their tetra-O-acetyl derivatives (10-18) were synthesized in total and evaluated for their biological properties, including antimicrobial and anticancer functions, and DNA/protein binding affinities. The compounds were prepared by firstly glycosylation and secondly acetylation methods. The structures of all compounds were elucidated by spectral analysis and the results showed that the glycoconjugates were obtained by diastereoselectivity as pure β- anomer. To observe cell proliferation, cytotoxicity and microdilution, different cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with pyrimidine N-β-D-glycosides (1-9) and their tetra-O-acetyl derivatives (10-18). These new carbohydrate conjugates and the controls showed the same non-toxic property to the cells, while 10-18 displayed lower cytotoxic potency than 1-9. And to support the experimental results of some compounds (8, 9, 17, and 18) whose pharmacological properties were determined, molecular docking studies were performed, which belonged to the in silico methods. The values of the binding parameters of these compounds with different receptors were determined by molecular docking. Studies on pathogenic bacteria revealed that both groups of new compounds exhibited significant antimicrobial activity with low concentrations (31.25-125 µg/mL). Significant data have been obtained indicating that they can bind to DNA via groove binding, with binding constants ranging from 1.1 × 103 to 4.0 × 104. In summary, preliminary information indicates that acetylated derivatives (10-18) have effective pharmacological properties.