Synthesis, crystallographic, computational and molecular docking studies of new acetophenone-benzoylhydrazones

A new series of hydrazones as small‐molecule aldose reductase inhibitors

“…Hydrazones have emerged as favorable ligands for the management of DM targeting a plethora of enzymes related to the pathogenesis of DM ranging from α‐glucosidase to AR due to their unique features allowing them to interact with key residues of biological targets. [ 16–24 ]…”

“…The aforementioned findings [ 16–27 ] encouraged us to design a novel series of tetrazole‐hydrazone hybrids as small‐molecule AR inhibitors. In this context, the facile and efficient synthesis of new hydrazones was carried out and in vitro and in silico studies were conducted to evaluate their potency as AR inhibitors.…”

“…[9][10][11][12][13][14][15] Hydrazones have emerged as favorable ligands for the management of DM targeting a plethora of enzymes related to the pathogenesis of DM ranging from α-glucosidase to AR due to their unique features allowing them to interact with key residues of biological targets. [16][17][18][19][20][21][22][23][24] Tetrazole stands out as a privileged motif ranking among the top 25 most commonly used nitrogen heterocycles in therapeutic agents. [25] Tetrazole is a well-known bioisostere of the carboxylic acid group, [26] which is found in AR inhibitors (e.g., epalrestat).…”

“…[11,27] The tetrazole scaffold is superior to the carboxylic acid group in terms of its enhanced metabolic stability and lipophilicity, which are important features for prolonged half-life and better membrane penetration, respectively. [26,27] The aforementioned findings [16][17][18][19][20][21][22][23][24][25][26][27] encouraged us to design a novel series of tetrazole-hydrazone hybrids as small-molecule AR inhibitors. In this context, the facile and efficient synthesis of new hydrazones was carried out and in vitro and in silico studies were conducted to evaluate their potency as AR inhibitors.…”