o-Hydroxycinnamic derivatives as prospective anti-platelet candidates: in silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y12 receptors

Abstract

Abstract Background The high prevalence of thrombotic abnormalities has become a major concern in the health sector. This is triggered by uncontrolled platelet aggregation, which causes complications and death. The problem becomes more complicated because of the undesirable side effects of the drugs currently in use, some of which have reportedly become resistant. This study aims to evaluate the potency of o-hydroxycinnamic acid derivatives (OCA1a–22a) and their pharmacokinetic properties and toxicity for them to be developed as new antiplatelet candidates. Methods In silico analysis of pharmacokinetics was carried out using pKCSM. Molecular docking of the compounds OCA 1a–22a was performed using the Molegro Virtual Docker. In silico evaluation of the potency of biological activity was done by measuring the bonding energy of each tested compound to the target receptor i.e. COX-1 and P2Y12, as the Moldock score (MDS). Results pKCSM analyses showed that more than 90% of OCA 1a–22a are absorbed through the intestine and distributed in plasma. Most tested compounds are not hepatotoxic, and none is mutagenic. An evaluation of the COX-1 receptor showed that OCA 2a–22a have lower binding energy compared to aspirin, which is the COX-1 inhibitor used today. So, it can be predicted that OCA 2–22a have stronger activity. Interactions with P2Y12 show lower MDS than aspirin, but slightly higher than ibuprofen, which is the standard ligand. Conclusions ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile prediction shows that OCA 1a–22a have the potential to be developed as oral preparations. OCA 1a–22a have strong potential to interact with COX-1 and P2Y12 receptors, so they are prospective anti-platelet candidates.