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

Autor: Mathew B; Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi-682 041, India., Herrera-Acevedo C; Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa, Brazil., Dev S; Department of Pharmaceutical Chemistry, Al-Shifa College of Pharmacy, Perinthalmanna - 679322, Kerala, India., Rangarajan TM; Department of Chemistry, Sri Venketeswara College, University of Delhi, New Delhi- 110021, India., Kuruniyan MS; Department of Dental Technology, College of Applied Medical Sciences, King Khalid University, Abha-61421, Saudi Arabia., Naseef PP; Department of Pharmaceutics, Moulana College of Pharmacy, Kerala-679321, India., Scotti L; Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa, Brazil., Scotti MT; Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa, Brazil.
Jazyk: angličtina
Zdroj: Combinatorial chemistry & high throughput screening [Comb Chem High Throughput Screen] 2022; Vol. 25 (10), pp. 1731-1744.
DOI: 10.2174/1386207324666210816125738
Abstrakt: 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 r 2 value of 0.76 and a Q 2 cv for cross-validation equal to 0.72. An external validation also was performed using 11 chalcones, obtaining a Q 2 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 (r 2 ) value of 0.76 and a Q 2 cv for cross-validation equal to 0.72 were obtained for this model. An external validation also was performed using 11 chalcones and a Q 2 ext value of 0.74 was found.
Conclusion: This report exhibited a good correlation and satisfactory agreement between experiment and theory.
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Databáze: MEDLINE
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