Lipase-catalyzed synthesis of 4-amino-3,5-dicyano-6-arylphthalates and in silico assessment of anti-Leishmanial activity

This study presented, for the first time, a method for synthesizing 4-amino-3,5-dicyano-6-aryl phthalates using porcine pancreatic lipase (PPL) as a catalyst. We synthesized 18 derivatives of 4-amino-3,5-dicyano-6-aryl phthalates employing aryl aldehyde, acetylenic esters, and malononitrile under optimal conditions for 4 h, with water serving as the primary reaction medium. The yields of the target products ranged from moderate to high, achieving 43 % to 95 %. This method demonstrates an excellent tolerance for various functional groups. Furthermore, this paper elucidates the reaction mechanism through molecular docking studies and confirms the interaction between the substrate and lipase. The data indicate that the measured distance from the substrate to the catalytic triad is 3.8 Å, with a binding energy of -4.6 kJ/mol, suggesting that PPL demonstrates the strongest catalytic potential in this specific reaction. Additionally, the aforementioned products underwent molecular docking analysis with three selected enzyme targets from Leishmania, highlighting their potential as lead compounds for anti-Leishmania activity.