Identification of Linomide Derivatives as Potential Anticancer Therapeutics using Molecular Docking Studies

12 analogs bearing a structural similarity to Linomide, a bonafide anticancer agent were synthesized wherein cyclization of substituted dianilides rendered 4-hydroxyquinolin-2(1H)-ones that were subjected to a Mannich reaction to yield 4-hydroxy-3-(substituted-1-ylmethyl) quinolin-2(1H)-one analogs....

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Frontiers in pharmacology 2022-06, Vol.13, p.892914-892914
Hauptverfasser: Borges e Soares, Giselle A., Bhattacharya, Tanima, Mamledesai, Shivalingrao, Ai, Zhaoquan, Hasan, Alexandru Madalin, Cavalu, Simona
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:12 analogs bearing a structural similarity to Linomide, a bonafide anticancer agent were synthesized wherein cyclization of substituted dianilides rendered 4-hydroxyquinolin-2(1H)-ones that were subjected to a Mannich reaction to yield 4-hydroxy-3-(substituted-1-ylmethyl) quinolin-2(1H)-one analogs. Characterization was performed using IR, 1 H nuclear magnetic resonance and 13 C NMR spectral analysis. Subsequently, in vitro anticancer studies revealed that Compound 4b showed maximum cytotoxicity with IC 50 values of 1.539 μM/ml and 1.732 μM/ml against A549 and K562 cell lines respectively. This, however, is lower in comparison with standard Paclitaxel (IC 50 values of 0.3 μM/ml for both cell lines). Surprisingly, docking studies at the active site of EGFRK revealed Compound 4b possessed a MolDock Score of -110.2253 that is highly comparable to the standard 4-anilinoquinazoline (MolDock Score of -112.04). Our computational and biological data thus provides an insight on the cytotoxicity of these derivatives and warrants future research that can possibly lead to the development of potent anticancer therapeutics.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.892914