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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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General Research Article

Development of 2D, 3D-QSAR and Pharmacophore Modeling of Chalcones for the Inhibition of Monoamine Oxidase B

Author(s): Bijo Mathew*, Chonny Herrera-Acevedo, Sanal Dev, T.M. Rangarajan, Mohamed Saheer Kuruniyan, Punnoth Poonkuzhi Naseef, Luciana Scotti and Marcus Tullius Scotti*

Volume 25, Issue 10, 2022

Published on: 16 August, 2021

Page: [1731 - 1744] Pages: 14

DOI: 10.2174/1386207324666210816125738

Price: $65

Abstract

Background: Selective and reversible types of MAO-B inhibitors have emerged as promising candidates for the management of neurodegenerative diseases. Several functionalized chalcone derivatives were shown to have potential reversible MAO-B inhibitory activity, which have recently been reported from our laboratory.

Methods: With the experimental results of about 70 chalcone derivatives, we further developed a pharmacophore modelling, and 2D and 3D- QSAR analyses of these reported chalcones for MAOB inhibition.

Results: The 2D-QSAR model presented four variables (MATS7v, GATS 1i and 3i, and C-006) from 143 Dragon 7 molecular descriptors, with a r2 value of 0.76 and a Q2 cv for cross-validation equal to 0.72. An external validation also was performed using 11 chalcones, obtaining a Q2 ext value of 0.74. The second 3D-QSAR model using MLR (multiple linear regression) was built starting from 128 Volsurf+ molecular descriptors, being identified as 4 variables (Molecular descriptors): D3, CW1 and LgS11, and L2LGS. Adetermination coefficient (r2) value of 0.76 and a Q2 cv for cross-validation equal to 0.72 were obtained for this model. An external validation also was performed using 11 chalcones and a Q2 ext value of 0.74 was found.

Conclusion: This report exhibited a good correlation and satisfactory agreement between experiment and theory.

Keywords: Chalcones, MAO-B, 2D-QSAR, 3D-QSAR, pharmacophore modeling, Q2 ext.

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