Design and Synthesis of Quinazolinone Tagged Acridones as Cytotoxic Agents and Their Effects on EGFR Tyrosine Kinase. Issue 9 (27th May 2014)

• Record Type: Journal Article
• Authors: Babu, Yarlagadda Rajesh; Bhagavanraju, Mantripragada; Reddy, Gade Deepak; Peters, Godefridus J.; Prasad, Velivela V. S. Rajendra
• Is Part Of: Archiv der Pharmazie. Volume 347:Issue 9(2014:Sep.)
• Page Start: 624
• Page End: 634
• Publication Date: 2014-05-27
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201400065
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201400065-sec-0001" sec-type="section"> <p>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 <bold>26</bold> showed relatively potent cytotoxic activity among the derivatives, against all the cell lines tested. Mechanistic studies for the selected derivatives <bold>7</bold>, <bold>8</bold>, <bold>16</bold>, <bold>17</bold>, <bold>25</bold>, and <bold>26</bold> were conducted through <italic>in vitro</italic> EGFR tyrosine kinase inhibition studies. The results indicate that compound <bold>26</bold> has a better EGFR tyrosine kinase inhibitory profile. The <italic>in vitro</italic> 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.</p> </sec> </abstract>