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Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

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Design, 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

https://doi.org/10.14233/ajchem.2020.22930
Nizamuddin Nagaladinne
Department of Research and Development, Jawaharlal Nehru Technological University Anantapur, Anathapuramu-515001, India
Abdul Ahad Hindustan
Department of Industrial Pharmacy, Raghavendra Institute of Pharmaceutical Education & Research, Ananthapuramu-515721, India
Devanna Nayakanti
Department of Chemistry, Oil Technological & Pharmaceutical Research Institute (OTPRI)-Jawaharlal Nehru Technological University Anantapur, Anathapuramu-515001, India

Corresponding Author(s) : Nizamuddin Nagaladinne

nnizamuddin1988@gmail.com

Asian Journal of Chemistry, Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020

Abstract

The present study involves the design, synthesis, characterization and molecular docking studies of biologically active quinazolin-4-ones, which were synthesized by condensing 2-amino-4-substituted phenylthiazole 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 in silico Swiss ADME. The colorectal anticancer screening was done by using cell HT-29 human colorectal adenocarcinoma based on molecular docking studies on 3GC7-the structure of p38alpha in complex with dihydroquinazolinone. Finally, compounds 5Dh8, 5DF6, 5Db2 and 5Di9 exhibited better activity at a concentration < 10 μg/mL when compared to 5-fluorouracil. The ADME properties revealed that all the compounds were within the range and docking studies showed the highest binding with glide score -7.19 and -7.027 Kcal/mol compared to the target protein -10.67 Kcal/mol.

Keywords

Quinazolin-4-ones Molecular docking Colorectal anticancer activity 2-Amino-1,3-phenylthiazole
Nagaladinne, N., Ahad Hindustan, A., & Nayakanti, D. (2020). Design, 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. Asian Journal of Chemistry, 32(12), 3067–3074. https://doi.org/10.14233/ajchem.2020.22930
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