Glutamic acid-catalyzed synthesis of dihydroquinazolinone: anticancer activity, electrochemical behavior, molecular docking, dynamics, simulations and drug-likeness studies

An efficient one-pot multi-component reaction (MCR) of 2,3-dihydro-4(1H)-quinazolinone derivative achieved by the reaction of aryl/heteroaryl aldehyde, isatoic anhydride and substituted aniline in ethanol catalyzed by novel glutamic acid (Glu) under microwave irradiation is described. In this work, derivatives 4m, 4o, 4q and 4r are novel compounds among the synthesized derivatives. For the first time, the electrochemical behavior studies for the selected derivatives were tested using cyclic voltammetry, compounds 4l, 4m, 4p, 4o, and 4q showed good reducing and oxidizing potential, due to the presence of the functional groups. Molecular docking studies of the selected compounds (4l–r) verified, among them highest docking scored 4r and 4m (− 8.572 and − 8.959 kcal/mol) molecules, respectively. Furthermore, MM/PBSA calculation identified key residues that contribute to the binding energy, activity and assessed cytotoxicity. The in vitro anticancer evaluation of the synthesized compounds was tested against human ovarian cancer PA-1 cell line tested; compounds 4r and 4m exhibited exceptionally anti-proliferative activity very close to the reference drug doxorubicin (3.66 ± 0.07) with the IC₅₀ value 7.53 ± 0.09 and 17.93 ± 0.12, respectively. According to swissADME study, the blood–brain barrier can be crossed majority of the derivatives tested, except 4n, and have high gastrointestinal absorption.

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