title: Molecular dynamics, density functional, ADMET predictions, virtual screening, and molecular interaction field studies for identification and evaluation of novel potential CDK2 inhibitors in cancer therapy.
abstract: In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter. One of the proposals and one of the drug-like compounds selected by virtual screening indicated to be promising candidates for CDK2-based cancer therapy.
authors.affiliation: Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Av. do Cafe, s/n, Monte Alegre 14040-903, Ribeirao Preto-SP, Brazil.
authors.forename: Vinicius Barreto
authors.initials: VB
authors.lastname: da Silva
authors.forename: Daniel Fábio
authors.initials: DF
authors.lastname: Kawano
authors.forename: Adriane da Silveira
authors.initials: Ada S
authors.lastname: Gomes
authors.forename: Ivone
authors.initials: I
authors.lastname: Carvalho
authors.forename: Carlton Anthony
authors.initials: CA
authors.lastname: Taft
authors.forename: Carlos Henrique Tomich de Paula
authors.initials: CH
authors.lastname: da Silva
mesh_terms: D000818:Animals; D019295:Computational Biology; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016208:Databases, Factual; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011789:Quantum Theory; D051381:Rats; D013816:Thermodynamics
chemical_list: D047428:Protein Kinase Inhibitors; D051357:Cyclin-Dependent Kinase 2