The Virtual Screening of Compounds from the ZINC Database against PARP-1 in Triple-Negative Breast Cancer

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Autor(es): dc.contributorSRM Institute of Science and Technology-
Autor(es): dc.contributorTexas Southern University-
Autor(es): dc.contributorIndia & Ennam College of Pharmacy-
Autor(es): dc.contributorSRM College of Pharmacy-
Autor(es): dc.contributorAnna University-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorPriyankha, Sridhar-
Autor(es): dc.creatorPolk, Shahrazad-
Autor(es): dc.creatorThilagavathi, Ramasamy-
Autor(es): dc.creatorPrakash, Muthuramalingam-
Autor(es): dc.creatorKathiravan, M. K.-
Autor(es): dc.creatorLakshmana Prabhu, Sakthivel-
Autor(es): dc.creatorBrunozi de Oliveira, Isabela-
Autor(es): dc.creatorSelvam, Chelliah-
Data de aceite: dc.date.accessioned2025-08-21T20:21:44Z-
Data de disponibilização: dc.date.available2025-08-21T20:21:44Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-03-11-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1002/slct.202304729-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/299587-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/299587-
Descrição: dc.descriptionTriple-negative breast cancer (TNBC) is the most aggressive kind of breast cancer that has disseminated worldwide, decimating millions of people. Especially, since it is capable of forming complex mutations, the design and development of effective drugs are much needed. Clinically, though talazoparib is an FDA-approved drug for PARP against advanced breast cancer, it has several adverse side effects such as anaemia, alopecia, neutropenia and thrombocytopenia. Herein, to understand the molecular interactions and mode of binding, 4.59 million lead-like compounds from the ZINC database were virtually screened against poly(ADP-ribose) polymerase-1 (PARP-1) protein using molecular docking. ADMET analysis were also performed for these compounds. Molecular dynamics (MD) simulations were conducted for a period of 100 ns for the best five compounds to validate the stability of the complexes. Root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and the radius of gyration (Rg) were analyzed and the number of hydrogen bonding interactions was identified to determine the structure and stability of these protein-ligand complexes. Further, binding free energy calculations were performed using the molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) approach to identify the effective anticancer agents. Z02, Z03, and Z04 have the highest binding affinity of −19.6, −18.1, and −18.1 kcal/mol, respectively, with PARP-1. They also have been found to strongly enhance the stability of the target. All things considered; we determine that compound Z04 is the most promising hit for TNBC.-
Descrição: dc.descriptionSRM Institute of Science and Technology-
Descrição: dc.descriptionDepartment of Chemistry SRM Institute of Science and Technology, Tamil Nadu, Chengalpattu District-
Descrição: dc.descriptionDepartment of Pharmaceutical Sciences Joan M. Lafleur College of Pharmacy and Health Sciences Texas Southern University, TX-
Descrição: dc.descriptionDepartment of Biotechnology Faculty of Engineering Karpagam Academy of Higher Education Coimbatore India & Ennam College of Pharmacy-
Descrição: dc.descriptionDepartment of Pharmaceutical Chemistry SRM College of Pharmacy, Chengalpattu District-
Descrição: dc.descriptionDepartment of Pharmaceutical Technology University College of Engineering (BIT Campus) Anna University-
Descrição: dc.descriptionDepartment of Physics Biosciences Languages and Exact Sciences Institute Sao Paulo State University Sao Jose do Rio Preto, SP-
Descrição: dc.descriptionDepartment of Physics Biosciences Languages and Exact Sciences Institute Sao Paulo State University Sao Jose do Rio Preto, SP-
Idioma: dc.languageen-
Relação: dc.relationChemistrySelect-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectMolecular dynamics simulations-
Palavras-chave: dc.subjectMolecular mechanics-Poisson-Boltzmann surface area-
Palavras-chave: dc.subjectPARP inhibitors-
Palavras-chave: dc.subjectPoly(ADP-ribose) polymerase-
Palavras-chave: dc.subjectTriple-negative breast cancer-
Título: dc.titleThe Virtual Screening of Compounds from the ZINC Database against PARP-1 in Triple-Negative Breast Cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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