P2Y1Rs (GPCRs) have pathophysiological importance, like immune system regulation, inflammation, blood aggregation and vascular system. Other than these, P2Y1R expressed in many cancers importantly, melanoma and prostate (PC3). In the current study alkyl chain-linked thiourea derivatives were investigated as P2Y1 receptor antagonists. Among the tested compounds, the most potent P2Y1R antagonists showed highest cell viability and they were non-toxic, compound 6q showed 49.66% cell viability in (MTT) assay. The Ca2+ mobilization assay was used to get the most potent antagonists of P2Y1 receptors, compounds 1q, 4q, 5q and 6q showed IC50 values 1.27, 0.133, 0.486 and 0.126 µM, respectively. They were inactive/non-selective against tP2Y1, hP2Y2, hP2Y and rP2Y6 receptors. Most of the compounds showed excellent predicted pharmacokinetic properties performed with SwissADME. The nature of interaction of most potent antagonists (1q, 4q,5q and 6q) of P2Y1 receptors was determine through molecular docking studies. The investigated antagonists showed same binding interactions in the active site of the receptors compared with standard antagonist (BPTU). The obtained results suggested that alkyl chain linked thiourea derivatives were P2Y1 receptor antagonists, the tested compounds could be suitable for anticancer drug development.

Key words: Antagonist Ca²⁺ assay, in silico studies, P2Y1R