Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents: Design, Synthesis, Biological Evaluation, SAR and In Silico Studies
- Authors
- Shyamlal, Bharti R. K.; Mathur, Manas; Yadav, Dharmendra K.; Mashevskaya, Irina, V; El-Shazly, Mohamed; Saleh, Na'il; Chaudhary, Sandeep
- Issue Date
- Mar-2022
- Publisher
- BENTHAM SCIENCE PUBL LTD
- Keywords
- 3-Phenyl-1H-isochromen-1-one; Sonogashira coupling; 6-endo-dig cyclization; antioxidant; DPPH; antiplatelet; arachidonic acid; structure-activity relationship
- Citation
- CURRENT PHARMACEUTICAL DESIGN, v.28, no.10, pp.829 - 840
- Journal Title
- CURRENT PHARMACEUTICAL DESIGN
- Volume
- 28
- Number
- 10
- Start Page
- 829
- End Page
- 840
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/85358
- DOI
- 10.2174/1381612827666211116102031
- ISSN
- 1381-6128
- Abstract
- Background: Several natural/synthetic molecules having a structure similar to 1H-isochromen-1-ones have been reported to display promising antioxidants and platelet aggregation inhibitory activity. Isocoumarin (1H-2-benzopyran-1-one) skeleton, either whole or as a part of the molecular framework, has been explored for its antioxidant or antiplatelet activities. Introduction: Based on the literature, a new prototype, i.e., 3-phenyl-1H-isochromen-1-ones based compounds, has been rationalized to possess both antioxidant as well as antiplatelet activities. Consequently, no reports are available regarding its inhibition either by cyclooxygenase-1 (COX-1) enzyme or by arachidonic acid (AA)-induced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxidant and antiplatelet agents. Methods: The goal of this work was to identify new 3-phenyl-1H-isochromen-1-ones based compounds via synthesis of a series of analogues, followed by performing in vitro antioxidant as well as AA-induced antiplatelet activities. Then, identification of potent compounds by SAR and molecular docking studies was carried out. Results: Out of all synthesized 3-phenyl-1H-isochromen-1-ones analogues, five compounds showed 7-fold to 16-fold more highly potent antioxidant activities than ascorbic acid. Altogether, ten 3-phenyl-1H-isochromen-1-one analogues displayed antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Almost all the 3-phenyl-1H-isochromen-1-one analogues exhibited potent AA-induced antiplatelet activity; few of them displayed 7-folds more activity as compared to aspirin. Further, in silico analysis validated the wet results. Conclusion: We disclose the first detailed study for the identification of 3-phenyl-1H-isochromen-1-one analogues as highly potent antioxidant as well as antiplatelet agents. The article describes the scaffold designing, synthesis, bioevaluation, structure-activity relationship, and in silky studies of a pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.
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