Open AccessDesign, Synthesis and Molecular Modelling Studies of 1-Methyl-3-(4-Substituted phenyl-1,3- thiazol-2-yl)-2-(pyridin-3-yl)-2,3-dihydroquinazolin-4(1H)-ones as Potent Anticancer Agents
Author(s) -
Nizamuddin Nagaladinne,
Abdul Ahad Hindustan,
N. Devanna
Publication year - 2020
Publication title -
asian journal of chemistry/asian journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.145
H-Index - 34
eISSN - 0975-427X
pISSN - 0970-7077
DOI - 10.14233/ajchem.2020.22930
Subject(s) - adme , chemistry , in silico , docking (animal) , stereochemistry , colorectal adenocarcinoma , combinatorial chemistry , in vitro , biochemistry , adenocarcinoma , medicine , nursing , cancer , gene
The present study involves the design, synthesis, characterization and molecular docking studies ofbiologically active quinazolin-4-ones, which were synthesized by condensing 2-amino-4-substitutedphenylthiazole with N-methylbenzoxazin-4-one. The N-methylbenzoxazin-4-one and 2-amino-4-substituted phenylthiazole were synthesized from N-methylanthranilic acid and substituted ketones,respectively. The ADME properties determined the synthetic accessibility of quinazolin-4-ones by insilico Swiss ADME. The colorectal anticancer screening was done by using cell HT-29 human colorectaladenocarcinoma based on molecular docking studies on 3GC7-the structure of p38alpha in complexwith dihydroquinazolinone. Finally, compounds 5Dh8, 5DF6, 5Db2 and 5Di9 exhibited better activityat a concentration < 10 μg/mL when compared to 5-fluorouracil. The ADME properties revealed thatall the compounds were within the range and docking studies showed the highest binding with glidescore -7.19 and -7.027 Kcal/mol compared to the target protein -10.67 Kcal/mol.