| Full text | |
| Author(s): Show less - |
Oliveira, Douglas Davison da Silva
;
Silva, Nagela Bernadelli Sousa
;
Lapierre, Thibault Joseph William Jacques Dit
;
de Souza, Sara Lemes
;
Brito, Nicolas Peterson Ferreira
;
Martinho, Ana Clara Cassiano
;
Dias, Renieidy Flavia Clemente
;
Farago, Danilo Nascimento
;
Michelan-Duarte, Simone
;
Chelucci, Rafael Consolin
;
Cruz, Mariza Gabriela Faleiro de Moura Lodi
;
Resende, Daniela de Melo
;
Andricopulo, Adriano D.
;
Murta, Silvane Maria Fonseca
;
Ferreira, Leonardo L. G.
;
Martins, Carlos Henrique Gomes
;
Rezende Junior, Celso de Oliveira
Total Authors: 17
|
| Document type: | Journal article |
| Source: | CHEMISTRY & BIODIVERSITY; v. N/A, p. 14-pg., 2024-11-07. |
| 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 mu g 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. (AU) | |
| FAPESP's process: | 15/50655-9 - FAPESP/MMV/DNDi/UNICAMP/USP Consortium to discover new drugs for the treatment of tropical parasitic diseases |
| Grantee: | Luiz Carlos Dias |
| Support Opportunities: | Research Grants - Research Partnership for Technological Innovation - PITE |
| FAPESP's process: | 18/14268-9 - Converting natural product leads into structure- and ligand-based drug discovery campaigns against Leishmaniasis and Chagas' Disease |
| Grantee: | Adriano Defini Andricopulo |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery |
| Grantee: | Glaucius Oliva |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |