IMPACT OF NOVEL THIAZOLE DERIVATE (R1), REVERSES PLATELET STRESS FIBER FORMATION ON FIBRINOGEN-COATED SURFACES: IN-VITRO AND IN-SILICO STUDIES

Abstract

Platelets aggregate and adhere to vascular damage sites to maintain hemostasis, but excessive activation can cause thrombotic disorders. Platelet shape changes precede aggregation or adhesion after physical or pharmacological stimulation. Unlike aggregation and adhesion, platelet shape alterations can be reversed. This dynamic phenomenon involves complex chemical signalling networks and many different cytoskeleton proteins. Novel thiazole compounds can prime platelet shape change, modulating thrombosis and preventing or developing thrombotic illnesses with reduced bleeding. In this article, we explained the current understanding of the mechanisms behind platelet shape change, its pathological implications, and potential therapeutic targets for controlling the associated cytoskeleton dynamics. The study investigated platelet spreading on the fibrinogen matrix to measure platelet activation. For platelet spreading, 12mm diameter circular cover slips were incubated with fibrinogen, and washed platelets were allowed to cling to immobilize proteins for a specific duration. Platelet adhesion and actin nodules or stress fibers were observed using a Compound Fluorescent Microscope. The in-silico studies used the AutoDockVina version for ligand binding for antiplatelet activity against the protein (PDB=1EQG and 3ZDY) and antioxidant activity against the protein (PDB=1HD2). Platelets treated with synthetic thiazole derivatives at concentrations of (0.01µM, 0.05µM, 0.1µM, 0.3µM, and 0.6µM) had significantly varying degrees of spreading. In-silico results indicated that the R1 thiazole derivative had negative binding energy (BE) values, -8.38 kcal/mol for PDB 1EQG and -7.17 kcal/mol for PDB 3ZDY, and -6.84 kcal/mol for PDB=1HD2, implying a greater ligand-binding affinity. The study concluded that the R1 novel thiazole derivative possesses significant antiplatelet action in response to fibrinogen activation of platelet aggregation at a concentration of 0.05 and 0.1µM. Molecular docking showed that the R1 derivative had higher antiplatelet and antioxidant activity than the standard compound, showing more significant antiplatelet action against the PDB-1EQG.