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.
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.
da Silva
Vinicius Barreto
VB
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.
Kawano
Daniel Fábio
DF
Gomes
Adriane da Silveira
Ada S
Carvalho
Ivone
I
Taft
Carlton Anthony
CA
da Silva
Carlos Henrique Tomich de Paula
CH
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
D047428:Protein Kinase Inhibitors; D051357:Cyclin-Dependent Kinase 2