Non‐peptide‐based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies. Issue 3 (9th March 2018) - Jaiswal, Pradeep K.
Abstract: A series of 2‐oxo‐2‐phenylethylidene linked 2‐oxo‐benzo[1, 4]oxazine analogues17a–x and18a–o, incorporated with a variety of electron‐withdrawing as well as electron‐donating groups at ring A and ring C, were synthesized under greener conditions in excellent yields (up to 98%). These analogues17a–x and18a–o were evaluated for their arachidonic acid (AA)‐induced platelet aggregation inhibitory activities in comparison with the standard reference aspirin (IC50 = 21.34 ± 1.09 µg/mL). Among all the screened compounds, eight analogues, 17i, 17x, 18f, 18g, 18h, 18i, 18l, and18o, were identified as promising platelet aggregation inhibitors as compared to aspirin. In addition, cytotoxic studies in 3T3 fibroblast cell lines by MTT assay of the promising compounds (17i, 17x, 18f–18i, 18l, and18o ) were also performed and the compounds were found to be non‐toxic in nature. Furthermore, the results on the AA‐induced platelet aggregation inhibitory activities of these compounds (17i, 17x, 18f–18i, 18l, and18o ) were validated via in silico molecular docking simulation studies. To the best of our knowledge, this is the first report of the identification of non‐peptide‐based functionalized 2‐oxo‐benzo[1, 4]oxazines as platelet aggregation inhibitors. Abstract : A series of 2‐oxo‐2‐phenylethylidene linked 2‐oxo‐benzo[1, 4]oxazine analogues were evaluated for their arachidonic acid‐induced platelet aggregation inhibitory activities. Eight analogues (17i, 17x, 18f, 18g, 18h, 18i, 18l, and18o ) were identified as promising platelet aggregation inhibitors as compared to aspirin. In silico molecular docking simulation studies confirm the found platelet aggregation inhibition activities.