Your browser doesn't support javascript.
loading
Discovery of Arylpiperazines with Broad-Spectrum Antimicrobial Activity and Favorable Pharmacokinetic Profiles.
Oliveira, Douglas Davison da Silva; Silva, Nagela Bernadelli Sousa; Lapierre, Thibault Joseph William Jacques Dit; de Souza, Sara Lemes; Brito, Nícolas Peterson Ferreira; Martinho, Ana Clara Cassiano; Clemente Dias, Renieidy Flávia; Farago, Danilo Nascimento; Michelan-Duarte, Simone; Chelucci, Rafael Consolin; Cruz, Mariza Gabriela Faleiro de Moura Lodi; de Melo Resende, Daniela; Andricopulo, Adriano D; Murta, Silvane Maria Fonseca; Ferreira, Leonardo L G; Gomes Martins, Carlos Henrique; de Oliveira Rezende Júnior, Celso.
Afiliação
  • Oliveira DDDS; Federal University of Uberlandia, Chemistry Institute, AV. JOÃO NAVES DE AVILA, 2121; UFU; INSTITUTO DE QUÍMICA, BL, Uberlândia, 38400-902, Uberlândia, BRAZIL.
  • Silva NBS; Federal University of Uberlandia, Biomedical Science, João Naves de Ávila, 38400-902, Uberlândia, BRAZIL.
  • Lapierre TJWJD; Federal University of Uberlandia, Chemistry Institute, João Naves, Uberlandia, BRAZIL.
  • de Souza SL; Federal University of Uberlandia, Biomedical Science, João Naves, uberlandia, BRAZIL.
  • Brito NPF; Federal University of Uberlandia, Chemistry Institute, João Naves, uberlandia, BRAZIL.
  • Martinho ACC; Federal University of Uberlandia, Chemistry Institute, joao naves, uberlandia, BRAZIL.
  • Clemente Dias RF; Federal University of Uberlandia, Chemistry Institute, joao naves, uberlandia, BRAZIL.
  • Farago DN; Federal University of Uberlandia, Chemistry Institute, joao naves, uberlandia, BRAZIL.
  • Michelan-Duarte S; University of São Paulo, Physics Institute, João Dagnone, são carlos, BRAZIL.
  • Chelucci RC; University of São Paulo, Physics Institute, João Dagnone, sao carlos, BRAZIL.
  • Cruz MGFML; Fiocruz Minas, Parasitology, Augusto de Lima, belo horizonte, BRAZIL.
  • de Melo Resende D; Fiocruz Minas, Parasitology, Augusto de Lima, belo horizonte, BRAZIL.
  • Andricopulo AD; University of São Paulo, Physics Institute, João Dagnone, sao carlos, BRAZIL.
  • Murta SMF; Fiocruz Minas, Parasitology, Augusto de Lima, belo horizonte, BRAZIL.
  • Ferreira LLG; University of São Paulo, Physics Institute, João Dagnone, sao carlos, BRAZIL.
  • Gomes Martins CH; Federal University of Uberlandia, Biomedical Science, joao naves, uberlandia, BRAZIL.
  • de Oliveira Rezende Júnior C; Universidade Federal de Uberlândia, Instituto de Química, Rua Nordau Gonçalves de Melo, 1232, 38408-208, Uberlândia, BRAZIL.
Chem Biodivers ; : e202402100, 2024 Sep 26.
Article em En | MEDLINE | ID: mdl-39327235
ABSTRACT
Microorganisms can induce diseases with significant clinical implications for human health. Multidrug-resistant microorganisms have been on the rise worldwide over the past few decades, and no new antibiotics have been introduced to the market in a considerable amount of time. Such situation highlights the urgency of discovering new antimicrobial drugs to address this pressing issue. Therefore, the objective of this study was to identify bioactive compounds against 15 species of bacteria and 5 species of fungi of clinical relevance through in vitro screening of 58 synthetic compounds from four chemical classes of our internal library of synthetic compounds. Our findings highlight arylpiperazines 18, 20, 26, 27, and 29, and the aminothiazole 50, as potent broad-spectrum antimicrobials (MICs = 12.5 - 15.6 mg.mL-1) against clinically relevant bacteria and fungi. Additionally, these compounds displayed low cytotoxicity against various host cells and a favorable in vitro pharmacokinetic profile for oral administration. Indeed, all six showed adequate lipophilicity, high gastrointestinal permeability, metabolic stability in human and mouse liver microsomes, and satisfactory aqueous solubility. Thus, they emerge as promising starting points for hit-to-lead studies towards new antibacterial and antifungal agents, especially against Staphylococcus epidermidis, Staphylococcus aureus, Lactobacillus paracasei and Candida orthopsilosis.
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Chem Biodivers Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Chem Biodivers Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça