Abstract
For the first time, a series of highly potent natural product inspired substituted (Z)-3-benzylideneisobenzofuran-1(3H)-ones 28a-t, embraced with electron-withdrawing groups (EWG) and electron-donating groups (EDG) at site I and site II, were prepared and assessed for their in vitro antioxidant activities (DPPH free radical scavenging assay) and arachidonic acid (AA)-induced antiplatelet activities using ascorbic acid (IC50 = 4.57 µg/mL) and aspirin (IC50 = 21.34 µg/mL), as standard references, respectively. In this study, compounds 28f-g, 28k-l and 28q have shown high order of in vitro antioxidant activity. Infact, 28f and 28k were found to show 10-folds and 8-folds more antioxidant activity than ascorbic acid, respectively and was found to be the most active analogues of the series. Similarly, Compounds 28c-g, 28k-l, 28o and 28q-t were recognized as highly potent antiplatelet agents (upto 6-folds) than aspirin. Furthermore, in silico studies of the most active antioxidants 28f, 28k and 28l and very active antiplatelet molecules 28f, 28k, 28l and 28s were carrying out for the validation of the biological results. This is the first detailed study of the discovery of several (Z)-3-benzylideneisobenzofuran-1(3H)-ones as highly potent antioxidants and antiplatelet agents.
Highlights
Efficacy in arachidonic acid (AA)-induced platelet aggregation (IC50 = 70 μM) in comparison to collagen-induced aggregation (IC50 = 120 μM) in washed rabbit platelets
We report the synthesis a series of functionalized (Z)-3-benzylidineisobenzofuran1(3H)-ones 28a-t, their antioxidant and AA-induced antiplatelet activities, and structure-activity relationship (SAR) studies
Various substituted (Z)-3-benzylidineisobenzofuran-1(3H)-ones 28a-t have shown high order of antioxidant and AA-induced antiplatelet activities using ascorbic acid and aspirin taken as standard reference, respectively
Summary
Similar studies further confirms the above facts[15,21] Overall, these studies revealed that (Z)-3-substituted-isobenzofuran-1(3H)-ones class of compounds exhibits AA-induced antiplatelet activities via inhibition of COX-120. There has been no detailed study on the AA-induced platelet aggregation inhibitory activities of (Z)-3-benzylidineisobenzofuran-1(3H)-ones. In our endeavor in search for novel bioactive heterocycles and based on the above facts, we have designed prototype 16 i.e. C-3 (Z)-benylidine-isobenzofuran-1(3H)-ones, incorporating similar sub-structural units of [1, 7] and [17,18,19,20,21,22,23,24,25] (Fig. 2) and assessed their antioxidant and AA-induced platelet aggregation inhibiting activities with the anticipation that the (Z)-3-benylidine-isobenzofuran-1(3H)-ones would show promising antioxidant as well as antiplatelet activity. We perform the in silico studies of most active compounds 28f, 28k, 28l and 28s for the validation of biological results
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