Benzoxazinone Derivatives as Antiplatelet: Synthesis, Molecular Docking, and Bleeding Time Evaluation

ABSTRACT

Background: The recurrence of atherosclerosis is still a global problem. Unfortunately, the drugs currently being used are reported to have resistance. Objectives: To prevent the recurrence of atherosclerosis disease, this study developed benzoxazinone derivatives as an antiplatelet agent: 2-phenyl-3,1-benzoxazine-4-one (BZ1) and 2-(4′-chlorophenyl)-3,1-benzoxazin-4-one (BZ2). Materials and Methods: The target compounds were synthesized through acyl nucleophilic substitution from acyl chloride and anthranilic acid using a base catalyst in triethylamine. This compound was then given to mice at three different doses to perform bleeding-time and clotting-time tests, using acetosal as a comparison. In silico, the binding energy between the test compound and the cyclooxygenase 1 enzyme was tested using Molegro Virtual Docker version 5.5 (MVD 5.5). The pharmacokinetic parameters were predicted using pharmacokinetics and chemistry through space mapping (pkCSM). Results: The synthesis provided 83% yield. The biological assay at a dose of 20 mg/kg body weight (BW) BZ1 showed a higher bleeding time (361 s) than acetosal (324 s), whereas BZ2 was lower (179 s). The molecular analysis revealed that the compound had higher activity than aspirin. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) showed that the compound posed high intestinal absorption. Conclusion: This research concluded that both of the synthesized compounds have the potential and prospective to be developed as antiplatelet agents.

KEYWORDS

• Benzoxazinone derivatives
• antiplatelet
• molecular docking
• pharmacokinetics and chemistry through space mapping
• cardiovascular disease

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• DOI10.1177/0976500X241305440Copy

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