Radhika Mane, Deepak A. Yaraguppi, Avinash Karkada Ashok, Bhavya Gangadharappa, K. B. Chandrakala, Kantharaju Kamanna
{"title":"Glutamic acid-catalyzed synthesis of dihydroquinazolinone: anticancer activity, electrochemical behavior, molecular docking, dynamics, simulations and drug-likeness studies","authors":"Radhika Mane, Deepak A. Yaraguppi, Avinash Karkada Ashok, Bhavya Gangadharappa, K. B. Chandrakala, Kantharaju Kamanna","doi":"10.1007/s11164-024-05305-6","DOIUrl":null,"url":null,"abstract":"<p>An efficient one-pot multi-component reaction (MCR) of 2,3-dihydro-4(1<i>H</i>)-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 <b>4m</b>, <b>4o</b>, <b>4q</b> and <b>4r</b> 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 <b>4l</b>, <b>4m</b>, <b>4p</b>, <b>4o,</b> and <b>4q</b> showed good reducing and oxidizing potential, due to the presence of the functional groups. Molecular docking studies of the selected compounds (<b>4l</b>–<b>r</b>) verified, among them highest docking scored <b>4r</b> and <b>4m</b> (− 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 <b>4r</b> and <b>4m</b> exhibited exceptionally anti-proliferative activity very close to the reference drug doxorubicin (3.66 ± 0.07) with the IC<sub>50</sub> 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 <b>4n</b>, and have high gastrointestinal absorption.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\n","PeriodicalId":753,"journal":{"name":"Research on Chemical Intermediates","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research on Chemical Intermediates","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11164-024-05305-6","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Research on Chemical Intermediates publishes current research articles and concise dynamic reviews on the properties, structures and reactivities of intermediate species in all the various domains of chemistry.
The journal also contains articles in related disciplines such as spectroscopy, molecular biology and biochemistry, atmospheric and environmental sciences, catalysis, photochemistry and photophysics. In addition, special issues dedicated to specific topics in the field are regularly published.