通过荧光测定、对接和qPCR评估噻嗪衍生物对MepA的抑制潜力

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-02-12 DOI:10.1016/j.genrep.2025.102162

Ana Carolina Justino de Araújo , Priscilla Ramos Freitas , Isaac Moura Araújo , João Arthur de Oliveira Borges , Ray Silva Almeida , José Bezerra de Araújo-Neto , Cícera Datiane de Moraes Oliveira-Tintino , Igor José dos Santos Nascimento , João Xavier de Araújo-Júnior , Edeildo Ferreira da Silva-Júnior , Thiago Mendonça de Aquino , Francisco Jaime Bezerra Mendonça Junior , Emmanuel Silva Marinho , Helcio Silva dos Santos , Julia Mariana Assis da Silva , Tereza Cristina Leal Balbino , Irwin Rose de Alencar Menezes , Saulo Relison Tintino , Henrique Douglas Melo Coutinho , Maria Flaviana Bezerra Morais Braga

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引用次数: 0

摘要

抗生素在治疗传染病方面至关重要，但细菌耐药性是一个严重的公共卫生问题，会增加成本并延长治疗时间。金黄色葡萄球菌（金黄色葡萄球菌），特别是菌株K2068，通过外排泵表现出耐药性，使治疗复杂化。为了解决这个问题，建议使用噻二嗪衍生物等替代品，它们是具有抗菌和药理特性的有前途的有机化合物。为了评估噻嗪衍生物对MepA泵的潜在作用，进行了直接抗菌活性测定、抗生素作用修饰、溴化乙啶测定、荧光法、分子对接和实时定量PCR （RT-qPCR）。虽然直接评价证明无效，但与溴化物和抗生素的相互作用显示出有希望的结果，表明衍生物活性。其他实验结果与微生物学分析结果一致，强调化合物IJ11的下调作用，使靶基因活性降低了约15倍。所有测试方法都证实噻嗪衍生物作为环丙沙星的盟友在对抗这种细菌菌株中的活性。

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Assessment of MepA inhibition potential using thiadiazine derivatives through fluorometry, docking, and qPCR

Antibiotics are crucial in treating infectious diseases, but bacterial resistance is a serious public health issue, increasing costs and prolonging treatments. Staphylococcus aureus (S. aureus), especially strain K2068, exhibits resistance through efflux pumps, complicating treatment. To combat this, alternatives such as thiadiazine derivatives, promising organic compounds with antimicrobial and pharmacological properties, are suggested. To assess the potential of thiadiazine derivatives against the MepA pump, direct antibacterial activity assays, antibiotic action modifying, and ethidium bromide assays, fluorimetry, molecular docking, and real-time quantitative PCR (RT-qPCR) were performed. Although direct evaluation proved ineffective, interaction with bromide and antibiotics showed promising results indicating derivative activity. The other assays performed corroborated with the results found in microbiological analyses, highlighting the down-regulation presented by compound IJ11, which reduced target gene activity by about 15 times. All tested methodologies confirmed the activity of thiadiazine derivatives as an ally of ciprofloxacin in combating this bacterial strain.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.