Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies.

Autor: Jaiswal PK; Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jaipur, India., Sharma V; Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jaipur, India., Kumar S; College of Pharmacy, Gachon University of Medicine and Science, Incheon City, Korea., Mathur M; Department of Advance Molecular Microbiology, Seminal Applied Sciences Pvt. Ltd., Jaipur, India., Swami AK; Department of Advance Molecular Microbiology, Seminal Applied Sciences Pvt. Ltd., Jaipur, India., Yadav DK; College of Pharmacy, Gachon University of Medicine and Science, Incheon City, Korea.; Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Jodhpur, Rajasthan, India., Chaudhary S; Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jaipur, India.
Jazyk: angličtina
Zdroj: Archiv der Pharmazie [Arch Pharm (Weinheim)] 2018 Apr; Vol. 351 (3-4), pp. e1700349. Date of Electronic Publication: 2018 Mar 09.
DOI: 10.1002/ardp.201700349
Abstrakt: A series of 2-oxo-2-phenylethylidene linked 2-oxo-benzo[1,4]oxazine analogues 17a-x and 18a-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 analogues 17a-x and 18a-o were evaluated for their arachidonic acid (AA)-induced platelet aggregation inhibitory activities in comparison with the standard reference aspirin (IC 50  = 21.34 ± 1.09 µg/mL). Among all the screened compounds, eight analogues, 17i, 17x, 18f, 18g, 18h, 18i, 18l, and 18o, were identified as promising platelet aggregation inhibitors as compared to aspirin. In addition, cytotoxic studies in 3T 3 fibroblast cell lines by MTT assay of the promising compounds (17i, 17x, 18f-18i, 18l, and 18o) 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, and 18o) 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.
(© 2018 Deutsche Pharmazeutische Gesellschaft.)
Databáze: MEDLINE
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