title: Design and synthesis of quinazolinone tagged acridones as cytotoxic agents and their effects on EGFR tyrosine kinase.
abstract: In a quest for finding potent cytotoxic molecules, we have designed and synthesized a new scaffold by tagging quinazolinones with an acridone moiety. The new acridone-4-carboximide derivatives were evaluated for their cytotoxic potentials against the MCF7 breast cancer cell line and three colon cancer cell lines (LS174T, SW1398, and WiDr). Compound 26 showed relatively potent cytotoxic activity among the derivatives, against all the cell lines tested. Mechanistic studies for the selected derivatives 7, 8, 16, 17, 25, and 26 were conducted through in vitro EGFR tyrosine kinase inhibition studies. The results indicate that compound 26 has a better EGFR tyrosine kinase inhibitory profile. The in vitro EGFR inhibition data was correlated with the cytotoxic properties, and molecular docking studies were performed with regard to the receptor autophosphorylation sites of the protein kinase domain of the EGFR.
authors.affiliation: Department of Pharmaceutical Chemistry, Gland Institute of Pharmaceutical Sciences, Narsapur, India.
authors.forename: Yarlagadda Rajesh
authors.initials: YR
authors.lastname: Babu
authors.forename: Mantripragada
authors.initials: M
authors.lastname: Bhagavanraju
authors.forename: Gade Deepak
authors.initials: GD
authors.lastname: Reddy
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: Velivela V S Rajendra
authors.initials: VV
authors.lastname: Prasad
mesh_terms: D054831:Acridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D052999:Quinazolinones / Q000737:chemistry*
chemical_list: D054831:Acridones; D000970:Antineoplastic Agents; D008024:Ligands; D052999:Quinazolinones; D066246:ErbB Receptors
keywords: Acridone; Breast cancer; Docking; EGFR