Novel β-L-1,3-thiazolidine pyrimidine nucleoside analogues: Design, synthesis, molecular docking, and anti-HIV activity

The remarkable activity of 1,3-thiazolidine pyrimidines against a variety of viruses has made them a viable class of antiviral medicines. These compounds exhibit a unique mechanism of action, targeting multiple stages of the viral life cycle, including viral entry, replication, and release. Moreover, their broad-spectrum antiviral activity and low cytotoxicity make them an attractive drug candidate for the treatment of viral infections. In this article, we detailed the synthesis of 1,3-thiazolidine pyrimidine derivatives substituted on the 5th position of the pyrimidine ring with different functional groups. The anti-HIV activity of the synthesized compounds was tested using the HIVRT assay. In comparison to the IC50 value of standard nevirapine (112.2 nM), the 1,3 thiazolidine pyrimidine compound substituted with Fluoro S4 (21.16 µM) and Bromo S5 (30.52 µM) only has moderate anti-HIV activity. Similarly, compounds S5 and S4 have a high affinity for the active site of HIV-1 reverse transcriptase, as evidenced by their docking scores of -89.5147 and -82.5556 kcal/mol, respectively.