Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor

The estrogen receptor alpha (ERα) plays an important role in breast development and pro-proliferation signal activation in the normal and cancerous breast. The ERα inhibitors were potentially active as cytotoxic agents against breast cancer. This study was conducted in order to find Asymmetrical Hex...

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Autores principales:	Hariyanti Hariyanti, Kusmadi Kurmardi, Arry Yanuar, Hayun Hayun
Formato:	article
Lenguaje:	EN
Publicado:	Department of Chemistry, Universitas Gadjah Mada 2020
Materias:	asymmetric hexahydro-2h-indazole analogs of curcumin aiacs estrogen receptor alpha inhibitor erα inhibitor pharmacophore modeling molecular docking breast cancer Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7e5ab35ec948407ebde5ecb7ed8e4031
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spelling	oai:doaj.org-article:7e5ab35ec948407ebde5ecb7ed8e40312021-12-02T14:02:46ZLigand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor1411-94202460-157810.22146/ijc.54745https://doaj.org/article/7e5ab35ec948407ebde5ecb7ed8e40312020-11-01T00:00:00Zhttps://jurnal.ugm.ac.id/ijc/article/view/54745https://doaj.org/toc/1411-9420https://doaj.org/toc/2460-1578The estrogen receptor alpha (ERα) plays an important role in breast development and pro-proliferation signal activation in the normal and cancerous breast. The ERα inhibitors were potentially active as cytotoxic agents against breast cancer. This study was conducted in order to find Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) as hits of ERα inhibitor. A training set of 17 selected ERα inhibitors was used to create 10 pharmacophore models using LigandScout 4.2. The pharmacophore models were validated using 383 active compounds as positive data and 20674 decoys as negative data obtained from DUD.E. Model 2 was found as the best pharmacophore model and consisted of three types of pharmacophore features, viz. one hydrophobic, one hydrogen bond acceptor, and aromatic interactions. Model 2 was utilized for ligand-based virtual screening 186 of AIACs, AMACs, intermediates, and Mannich base derivative compounds. The hits obtained were further screened using molecular docking, analyzed using drug scan, and tested for its synthesis accessibility. Fourteen compounds were fulfilled as hits in pharmacophore modeling, in which 10 hits were selected by molecular docking, but only seven hits met Lipinski’s rule of five and had medium synthesis accessibility. In conclusion, seven compounds were suggested to be potentially active as ERα inhibitors and deserve to be synthesized and further investigated.Hariyanti HariyantiKusmadi KurmardiArry YanuarHayun HayunDepartment of Chemistry, Universitas Gadjah Madaarticleasymmetric hexahydro-2h-indazole analogs of curcuminaiacsestrogen receptor alpha inhibitorerα inhibitorpharmacophore modelingmolecular dockingbreast cancerChemistryQD1-999ENIndonesian Journal of Chemistry, Vol 21, Iss 1, Pp 137-147 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	asymmetric hexahydro-2h-indazole analogs of curcumin aiacs estrogen receptor alpha inhibitor erα inhibitor pharmacophore modeling molecular docking breast cancer Chemistry QD1-999
spellingShingle	asymmetric hexahydro-2h-indazole analogs of curcumin aiacs estrogen receptor alpha inhibitor erα inhibitor pharmacophore modeling molecular docking breast cancer Chemistry QD1-999 Hariyanti Hariyanti Kusmadi Kurmardi Arry Yanuar Hayun Hayun Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
description	The estrogen receptor alpha (ERα) plays an important role in breast development and pro-proliferation signal activation in the normal and cancerous breast. The ERα inhibitors were potentially active as cytotoxic agents against breast cancer. This study was conducted in order to find Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) as hits of ERα inhibitor. A training set of 17 selected ERα inhibitors was used to create 10 pharmacophore models using LigandScout 4.2. The pharmacophore models were validated using 383 active compounds as positive data and 20674 decoys as negative data obtained from DUD.E. Model 2 was found as the best pharmacophore model and consisted of three types of pharmacophore features, viz. one hydrophobic, one hydrogen bond acceptor, and aromatic interactions. Model 2 was utilized for ligand-based virtual screening 186 of AIACs, AMACs, intermediates, and Mannich base derivative compounds. The hits obtained were further screened using molecular docking, analyzed using drug scan, and tested for its synthesis accessibility. Fourteen compounds were fulfilled as hits in pharmacophore modeling, in which 10 hits were selected by molecular docking, but only seven hits met Lipinski’s rule of five and had medium synthesis accessibility. In conclusion, seven compounds were suggested to be potentially active as ERα inhibitors and deserve to be synthesized and further investigated.
format	article
author	Hariyanti Hariyanti Kusmadi Kurmardi Arry Yanuar Hayun Hayun
author_facet	Hariyanti Hariyanti Kusmadi Kurmardi Arry Yanuar Hayun Hayun
author_sort	Hariyanti Hariyanti
title	Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
title_short	Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
title_full	Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
title_fullStr	Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
title_full_unstemmed	Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor
title_sort	ligand based pharmacophore modeling, virtual screening, and molecular docking studies of asymmetrical hexahydro-2h-indazole analogs of curcumin (aiacs) to discover novel estrogen receptors alpha (erα) inhibitor
publisher	Department of Chemistry, Universitas Gadjah Mada
publishDate	2020
url	https://doaj.org/article/7e5ab35ec948407ebde5ecb7ed8e4031
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Ligand Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ERα) Inhibitor

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