TY - JOUR
T1 - Discovery of Natural Product Inspired 3-Phenyl-1H-isochromen-1-ones as Highly Potent Antioxidant and Antiplatelet Agents
T2 - Design, Synthesis, Biological Evaluation, SAR and In Silico Studies
AU - Shyamlal, Bharti R.K.
AU - Mathur, Manas
AU - Yadav, Dharmendra K.
AU - Mashevskaya, Irina V.
AU - El-Shazly, Mohamed
AU - Saleh, Na’Il
AU - Chaudhary, Sandeep
N1 - Funding Information:
The stdy has been funded by the Science & Engineering Research Board (SERB) [CRG/2019/005102], New Delhi, and the Ministry of Education and Science, Perm, Russian Federation [agreement no. C-26/174.5 dated 31-01-2019].
Publisher Copyright:
© 2022 Bentham Science Publishers.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - 3-Phenyl-1H-isochromen-1-one
KW - 6-endo-dig cyclization
KW - DPPH
KW - Sonogashira coupling
KW - antioxidant
KW - antiplatelet
KW - arachidonic acid
KW - structure-activity relationship
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U2 - 10.2174/1381612827666211116102031
DO - 10.2174/1381612827666211116102031
M3 - Article
C2 - 34784855
AN - SCOPUS:85130204610
SN - 1381-6128
VL - 28
SP - 829
EP - 840
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 10
ER -