A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S-aureus and E-faecium Infections

被引：11

作者：

Campanini-Salinas, Javier ^{[1
,2
]}

Andrades-Lagos, Juan ^{[1
]}

Gonzalez Rocha, Gerardo ^{[3
]}

Choquesillo-Lazarte, Duane ^{[4
]}

Bollo Dragnic, Soledad ^{[5
]}

Faundez, Mario ^{[6
]}

Alarcon, Pedro ^{[7
]}

Silva, Francisco ^{[8
]}

Vidal, Roberto ^{[9
]}

Salas-Huenuleo, Edison ^{[10
]}

Kogan, Marcelo ^{[10
]}

Mella, Jaime ^{[11
,12
]}

Recabarren Gajardo, Gonzalo ^{[13
]}

Vasquez-Velasquez, David ^{[1
]}

机构：

[1] Univ Chile, Fac Chem & Pharmaceut Sci, Drug Dev Lab, Sergio Livingstone 1007, Santiago 8380492, Chile

[2] Univ San Sebastian, Fac Med & Ciencia, Panguipulli 1390, Lago 5501842, Puerto Montt, Chile

[3] Univ Concepcion, Fac Ciencias Biol, Dept Microbiol, Lab Invest Agentes Antibacterianos, Concepcion 4070386, Chile

[4] CSIC UGR, IACT, Lab Estudios Cristalog, Av Palmeras 4, Armilla 18100, Granada, Spain

[5] Univ Chile, Fac Chem & Pharmaceut, Bioelectrochem Lab, Sci, Santiago 8380492, Chile

[6] Pontificia Univ Catolica Chile, Fac Chem, Pharm Dept, Mol Pharmacol & Toxicol Lab, Santiago 7820436, Chile

[7] Inst Salud Publ Chile, Agents Bacterial Meningitis Lab, Santiago 7780050, Chile

[8] Clin Hosp Univ Chile, Microbiol Unit, Clin Lab, Santiago 8380456, Chile

[9] Univ Chile, Fac Med, Biomed Sci Inst, Antibiot Lab,Microbiol Program, Santiago 8380453, Chile

[10] Univ Chile, Fac Chem & Pharmaceut Sci, Nanobiotechnol & Nanotoxicol Lab, Santiago 8380494, Chile

[11] Univ Valparaiso, Fac Sci, Inst Chem & Biochem, Valparaiso 2360102, Chile

[12] Univ Andres Bello, Fac Med, Escuela Quim & Farm, Quillota 980, Vina Del Mar 2531015, Chile

[13] Pontificia Univ Catolica Chile, Pharm Dept, Lab Synth Bioact Heterocycles, Fac Chem, Santiago 7820436, Chile

来源：

MOLECULES | 2018年 / 23卷 / 07期

关键词：

quinonic-antibiotics; methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococcus faecium; antibacterial activity; IN-VITRO ACTIVITY; GRAM-POSITIVE PATHOGENS; BIOLOGICAL EVALUATION; ANTIBACTERIAL AGENTS; 1,4-NAPHTHOQUINONE DERIVATIVES; COMPLICATED SKIN; NATURAL-PRODUCTS; PRODRUG TR-701; MARINE SPONGE; UNITED-STATES;

D O I：

10.3390/molecules23071776

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC((R)) strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1-32 g/mL against Gram-positive ATCC((R)) strains. The structure-activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 mu g/mL and 4/4 mu g/mL, respectively, while for vancomycin the MIC50/90 was 256/512 mu g/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.

引用

页数：19

共 48 条

[41] Studies on quinones. Part 44: Novel angucyclinone N-heterocyclic analogues endowed with antitumoral activity [J].