3-Oxopyridazin-5-yl-Chalcone Hybrids: Potent Antiplatelet Agents That Prevent Glycoprotein IIb/IIIa Activation

Abstract

A novel family of potent and broad‐spectrum antiplatelet agents has been discovered by exploration of a library of 3‐oxopyridazin‐5‐yl‐chalcone hybrids. The pharmacological evaluation of the collection established the most salient features of the SAR in this series and allowed the identification of lead compounds that exhibit antiplatelet activity that is substantially superior to drugs in clinical use and 3,4‐methylenedioxy‐β‐nitrostyrene (MNS). The derivatives reported herein act on GPIIb/IIIa, but in a different manner to classical antagonists (e. g., tirofiban), by preventing GPIIb/IIIa activation. Given their mechanism of action, these compounds might avoid the adverse effects of antagonists (paradoxical GPIIb/IIIa activation) and constitute attractive pharmacological tools for the development of tailored agents for the treatment of platelet‐dependent thrombosis.

Exploring the Antioxidant Potency of New Naphthalene‐Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations

“…To demonstrate the antioxidant potential of the newly synthesized compounds (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), their radical-scavenging capacities were determined using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. [31] This method is based on the ability of the DPPH radical to abstract H-atoms from antioxidants (AÀ H) to form the hydrazine derivative DPPHÀ H Figure 1, as depicted in reaction 1.…”

“…A wide range of pharmacological applications has been reported for chalcone derivatives incorporating a heterocyclic scaffold, which includes antioxidant, antibacterial, anticancer, antiplatelet, and anti-inflammatory activities. [6][7][8][9][10][11] Among these properties, the antioxidant properties of chalcone derivatives have been extensively investigated. [12] It is reported that chalcones with proper functional substituents (e. g., OH or NH) can exhibit a great efficacy in antioxidant activity due to their potent abilities to scavenge ROS directly through hydrogen or electron transfer.…”

“…Furthermore, chalcones have been utilized as versatile precursors to design and synthesize a plethora of pharmacologically active NSO‐heterocyclic systems through reaction with various bi‐nucleophilic reagents, e. g., hydrazine and its derivatives, thiourea, and guanidine. A wide range of pharmacological applications has been reported for chalcone derivatives incorporating a heterocyclic scaffold, which includes antioxidant, antibacterial, anticancer, antiplatelet, and anti‐inflammatory activities [6–11] . Among these properties, the antioxidant properties of chalcone derivatives have been extensively investigated [12] .…”

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review

“…On top of this, many researchers are exhaustively devoted to synthesizing a chalcone derivative incorporating a heterocyclic scaffold. Chalcones incorporating heterocyclic scaffolds have been reported with various biological and pharmacological activities, such as antioxidant activity, 12 antibacterial activity, 12 antifungal activity, 13 antileishmanial activity, 14 anti-inflamatory activity, 15 anticancer activity, 16 antitubercular activity, 17 antiproliferative agents, 17 antimalarial activity, 18 antiplatelet activity, 19 carbonic anhydrase inhibitors, 20 an inhibitor of microsomalenzyme glutathione-S-transferases, 21 and CYP1 enzyme inhibitors. 22 Chalcones with an N-heterocyclic moiety such as pyrrole, imidazole, thiazole, pyrazole, oxazole, isooxazole, pyridine, pyrazoline, indole, benzothiazole, benzimidazole, and quinoline scaffolds play a significant role in the area of medicine.…”

(E)-1-(4-Hydroxyphenyl)-3-(substituted-phenyl) prop-2-en-1-ones: Synthesis, In Vitro Cytotoxic Activity and Molecular Docking Studies

“…Chalcone is an important chemo type that has attracted great research interest for decades due to the abundant natural chalcone-based compounds, the easy synthesis and derivatization, and most importantly, the diverse biological activities of various chalcone-based compounds. [1][2][3][4][5][6] The well documented biological activities of chalcones include anti-HIV, 7 antibacterial, 8 anti-cancer and antioxidant, [9][10][11] antituberculosis agents, 12 anti-prolif-erative, 13 antiplatelet, 14,15 and antimalarial. 16,17 Numerous studies have attempted to elucidate the mechanisms of action and target interactions responsible for these biological activities.…”