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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*   Pages 1 - 14 ( 14 )

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.

Affiliation:

Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi-682 041, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa, Department of Pharmaceutical Chemistry, Al-Shifa College of Pharmacy, Perinthalmanna – 679322, Kerala, Department of Chemistry, Sri Venketeswara College, University of Delhi, New Delhi-110021, Department Dental Technology, COAMS, King Khalid university, Abha, Department of Pharmaceutics, Moulana College of Pharmacy, Kerala, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900, João Pessoa



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