Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening

Suhas M. Shelke; Sharad H. Bhosale; Radha Charan Dash; Mugdha R. Suryawanshi; Kakasaheb R. Mahadik

doi:10.1016/j.bmcl.2011.02.072

Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening

Suhas M. Shelke, Sharad H. Bhosale, Radha Charan Dash, Mugdha R. Suryawanshi, Kakasaheb R. Mahadik

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.

Original language	English (US)
Pages (from-to)	2419-2424
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2011.02.072
State	Published - Apr 15 2011
Externally published	Yes

Keywords

3D-QSAR
Docking
MAO-A inhibitors
Pharmacophore
in silico screening

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2011.02.072

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title = "Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening",

abstract = "Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.",

keywords = "3D-QSAR, Docking, MAO-A inhibitors, Pharmacophore, in silico screening",

author = "Shelke, {Suhas M.} and Bhosale, {Sharad H.} and Dash, {Radha Charan} and Suryawanshi, {Mugdha R.} and Mahadik, {Kakasaheb R.}",

note = "Funding Information: One of the authors (S.M.S.) is indebted to Council of Scientific and Industrial Research (CSIR), New Delhi, India, for awarding senior research fellowship. Authors wish to express their gratitude towards Dr. R. A. Joshi and Dr. (Mrs.) R. R. Joshi, National Chemical Laboratory, Pune, India, for their support. ",

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AU - Shelke, Suhas M.

AU - Bhosale, Sharad H.

AU - Dash, Radha Charan

AU - Suryawanshi, Mugdha R.

AU - Mahadik, Kakasaheb R.

N1 - Funding Information: One of the authors (S.M.S.) is indebted to Council of Scientific and Industrial Research (CSIR), New Delhi, India, for awarding senior research fellowship. Authors wish to express their gratitude towards Dr. R. A. Joshi and Dr. (Mrs.) R. R. Joshi, National Chemical Laboratory, Pune, India, for their support.

PY - 2011/4/15

Y1 - 2011/4/15

N2 - Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.

AB - Monoamine oxidase-A (MAO-A) inhibitors are of particular importance in the treatment of depressive disorders. Herein described is pharmacophore generation and atom-based 3D-QSAR analysis of previously reported pyrrole based MAO-A inhibitors in order to get insight into their structural requirements responsible for high affinity. The best pharmacophore model generated consisted of four features DHHR: a hydrogen bond donor (D), two hydrophobic groups (H) and an aromatic ring (R). Based on model generated, a statistically valid 3D-QSAR with good predictability was developed. Derived pharmacophore was used as a query to search Zinc 'clean drug-like' database. Hits retrieved were passed progressively through filters like fitness score, predicted activity and docking scores. The survived hits present new scaffolds with a potential for MAO-A inhibition.

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Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening

Abstract

Keywords

ASJC Scopus subject areas

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