Quinazoline-tethered thiazolo[3,2-a]pyrimidines and their cyclic chalcone derivatives as HIV-1 reverse transcriptase inhibitors: green synthesis, molecular docking, and in silico studies.

Nitrogen-fused heterocycles have attracted considerable research interest in pharmaceutical, medicinal, organometallic, and materials chemistry. In this work, two new series of quinazoline-linked thiazolo[3,2-a]pyrimidines and their cyclic chalcone derivatives were synthesized using choline hydroxide as an environmentally friendly catalyst. The synthesized compounds were evaluated for their inhibitory activity against HIV-1 reverse transcriptase (RT). Compound 11e showed the highest inhibitory activity, with an IC50 value of 0.599 µg mL-1 (1.305 µM). Molecular docking was performed to examine the possible binding modes and interactions within the active site of the enzyme. However, only a weak correlation was observed between the docking scores and experimental IC50 values (Pearson's r ≈ -0.18), indicating that the docking results provide qualitative binding information rather than a direct prediction of the inhibitory activity. In silico ADMET analysis also indicated generally favorable oral drug-like properties. These findings suggest that the synthesized compounds, particularly 11e, may serve as preliminary leads for the further development of HIV-1 RT inhibitors.