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

Bharti R.K. Shyamlal, Manas Mathur, Dharmendra K. Yadav, Irina V. Mashevskaya, Mohamed El-Shazly, Na’Il Saleh, Sandeep Chaudhary

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Several natural/synthetic molecules having a structure similar to 1H-isochro-men-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)-in-duced platelet aggregation. This prompted us to investigate 3-phenyl-1H-isochromen-1-ones towards antioxi-dant 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-isochro-men-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 silico studies of a pharmaceutically privileged bioactive 3-phenyl-1H-isochromen-1-one class of heterocycles.

Original languageEnglish
Pages (from-to)829-840
Number of pages12
JournalCurrent Pharmaceutical Design
Volume28
Issue number10
DOIs
Publication statusPublished - 2022

Keywords

  • 3-Phenyl-1H-isochromen-1-one
  • 6-endo-dig cyclization
  • DPPH
  • Sonogashira coupling
  • antioxidant
  • antiplatelet
  • arachidonic acid
  • structure-activity relationship

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this