Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach

<b data-eusoft-scrollable-element="1">Background:</b> Prostate cancer is the most common cancer in men, especially after the age of 50. It is a malignant disease that is increasing due to the increased life expectancy of the world population. Its development and progression are...

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Main Authors: Norberto S. Costa, Lúcio R. Lima, Jorddy N. Cruz, Igor V. F. Santos, Rai C. Silva, Alexandre A. Maciel, Elcimar S. Barros, Maracy L. D. S. Andrade, Ryan S. Ramos, Njogu M. Kimani, Alberto Aragón-Muriel, Juan M. Álvarez-Caballero, Joaquín M. Campos, Cleydson B. R. Santos
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Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/6/888
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author Norberto S. Costa
Lúcio R. Lima
Jorddy N. Cruz
Igor V. F. Santos
Rai C. Silva
Alexandre A. Maciel
Elcimar S. Barros
Maracy L. D. S. Andrade
Ryan S. Ramos
Njogu M. Kimani
Alberto Aragón-Muriel
Juan M. Álvarez-Caballero
Joaquín M. Campos
Cleydson B. R. Santos
author_facet Norberto S. Costa
Lúcio R. Lima
Jorddy N. Cruz
Igor V. F. Santos
Rai C. Silva
Alexandre A. Maciel
Elcimar S. Barros
Maracy L. D. S. Andrade
Ryan S. Ramos
Njogu M. Kimani
Alberto Aragón-Muriel
Juan M. Álvarez-Caballero
Joaquín M. Campos
Cleydson B. R. Santos
author_sort Norberto S. Costa
collection DOAJ
description <b data-eusoft-scrollable-element="1">Background:</b> Prostate cancer is the most common cancer in men, especially after the age of 50. It is a malignant disease that is increasing due to the increased life expectancy of the world population. Its development and progression are dependent on androgenic stimulation. <b data-eusoft-scrollable-element="1">Objectives:</b> This study aimed to identify potential inhibitors with anti-prostate cancer activity through the application of chemoinformatics tools, exploring the Princeton (~1.2 million compounds) and Zinc Drug (~175 million compounds) databases. <b data-eusoft-scrollable-element="1">Methods:</b> The methodology used several computational techniques, such as ROCS (Rapid Chemical Structure Superposition) and EON (Electrostatic Potential Screening), predictions of pharmacokinetic and toxicological properties, molecular docking, synthetic accessibility, biological activity, and molecular dynamics. <b data-eusoft-scrollable-element="1">Results:</b> At the end of all these virtual screening steps, the study resulted in four promising potential candidates for the treatment of prostate cancer: the molecules ZINC34176694, ZINC03876158, ZINC04097308, and ZINC03977981, which exhibited all the desirable pharmacokinetic parameters (ADME/Tox) for a potential drug. <b data-eusoft-scrollable-element="1">Conclusions:</b> Docking and molecular dynamics studies demonstrate stability and interaction with the androgen receptor of the selected compounds, showing them to be promising candidates for the development of new drugs.
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spelling doaj-art-12f54b9bb45143d2be0290abb91c8b272025-08-20T02:21:49ZengMDPI AGPharmaceuticals1424-82472025-06-0118688810.3390/ph18060888Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics ApproachNorberto S. Costa0Lúcio R. Lima1Jorddy N. Cruz2Igor V. F. Santos3Rai C. Silva4Alexandre A. Maciel5Elcimar S. Barros6Maracy L. D. S. Andrade7Ryan S. Ramos8Njogu M. Kimani9Alberto Aragón-Muriel10Juan M. Álvarez-Caballero11Joaquín M. Campos12Cleydson B. R. Santos13Graduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilGraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilLaboratory of Modeling and Computational Chemistry, Department of Biological and Health Sciences, Federal University of Amapá, Macapa 68902-280, AP, BrazilNatural Product Chemistry and Computational Drug Discovery Laboratory, University of Embu, Embu P.O. Box 6-60100, KenyaGrupo de Investigaciones Bioquímicas, Universidad del Magdalena, Santa Marta CP 470004, ColombiaGrupo de Química y Bioprospección de Productos Naturales, Departamento de Química, Universidad del Magdalena, Santa Marta CP 470004, ColombiaDepartment of Pharmaceutical and Organic Chemistry, Faculty of Pharmacy, Campus of Cartuja, University of Granada, 18071 Granada, SpainGraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Macapa 68902-280, AP, Brazil<b data-eusoft-scrollable-element="1">Background:</b> Prostate cancer is the most common cancer in men, especially after the age of 50. It is a malignant disease that is increasing due to the increased life expectancy of the world population. Its development and progression are dependent on androgenic stimulation. <b data-eusoft-scrollable-element="1">Objectives:</b> This study aimed to identify potential inhibitors with anti-prostate cancer activity through the application of chemoinformatics tools, exploring the Princeton (~1.2 million compounds) and Zinc Drug (~175 million compounds) databases. <b data-eusoft-scrollable-element="1">Methods:</b> The methodology used several computational techniques, such as ROCS (Rapid Chemical Structure Superposition) and EON (Electrostatic Potential Screening), predictions of pharmacokinetic and toxicological properties, molecular docking, synthetic accessibility, biological activity, and molecular dynamics. <b data-eusoft-scrollable-element="1">Results:</b> At the end of all these virtual screening steps, the study resulted in four promising potential candidates for the treatment of prostate cancer: the molecules ZINC34176694, ZINC03876158, ZINC04097308, and ZINC03977981, which exhibited all the desirable pharmacokinetic parameters (ADME/Tox) for a potential drug. <b data-eusoft-scrollable-element="1">Conclusions:</b> Docking and molecular dynamics studies demonstrate stability and interaction with the androgen receptor of the selected compounds, showing them to be promising candidates for the development of new drugs.https://www.mdpi.com/1424-8247/18/6/888prostate cancerantiandrogenvirtual screeningmolecular dockingmolecular dynamics
spellingShingle Norberto S. Costa
Lúcio R. Lima
Jorddy N. Cruz
Igor V. F. Santos
Rai C. Silva
Alexandre A. Maciel
Elcimar S. Barros
Maracy L. D. S. Andrade
Ryan S. Ramos
Njogu M. Kimani
Alberto Aragón-Muriel
Juan M. Álvarez-Caballero
Joaquín M. Campos
Cleydson B. R. Santos
Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
Pharmaceuticals
prostate cancer
antiandrogen
virtual screening
molecular docking
molecular dynamics
title Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
title_full Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
title_fullStr Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
title_full_unstemmed Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
title_short Identification of Inhibitors with Potential Anti-Prostate Cancer Activity: A Chemoinformatics Approach
title_sort identification of inhibitors with potential anti prostate cancer activity a chemoinformatics approach
topic prostate cancer
antiandrogen
virtual screening
molecular docking
molecular dynamics
url https://www.mdpi.com/1424-8247/18/6/888
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