Urea and thiourea derivatives of dipeptides conjugated piperazine analogue as a new class of age's inhibitors: synthesis and molecular docking studies

A novel class of urea and thiourea derivatives of dipeptides conjugated 2, 3-dichlorophenyl piperazine were synthesized and evaluated for their AGEu0027s inhibition capacity. Antiglycation assay was performed by assessing fluorescence spectrum (exitation 370 nm), and change in fluorescence intensity (to emission 440 nm), based on AGEs were monitored by using spectrofluorimeter. Our results indicate that fluoro containing dipeptide-PZN derivatives have shown excellent curative potential. Interestingly, compounds 6, 7, 14, 15, 22, 23, 30 and 31 have shown excellent potency with IC50 values 13.5 ± 0.77, 8.0 ± 0.25, 14.5 ± 0.92, 7.8 ±0.44, 9.1 ± 0.41, 3.1 ± 0.45, 9.2 ± 0.80 and 2.5 ± 0.55, compared to the standard, rutin 41.9 μM. From our studies, we may draw certain conclusions like Lys containing dipeptides may serve as good antiglycating agents. On the other hand, itu0027s felt worthy to consider substitutions particularly at para position for the increase in potency. The IC50 values of the compounds were compared with the glide scores from the molecular studies. It was observed that the main interaction force of compounds with the active site was hydrophobic. The IC50 values and glide scores have exhibited better correlation. Thus, this synthetic novel urea and thioureas of dipeptide containing compounds may lead potent antiglycating agents.