Scholarlink

<p>NDM-1-KP ST 147 remains a serious challenge in clinical practice, primarily due to its increasing resistance to carbapenems and its hypervirulent characteristics. A range of virulence factors is involved in this hypervirulence, and the mechanisms underlying carbapenem resistance are complex and multifaceted. The NDM KP (ST147) has emerged as a recent addition to the family of successful clones within the species. In this study, we synthesized methyl 3-(4-chlorobenzamido)-4-methylthiophene-2-carboxylate (<b>3</b>) by reacting amino thiophene (<b>1</b>) with 4-bromobenzoic acid (<b>2</b>) in the presence of TiCl<sub>4</sub> (catalyst) and pyridine. The Suzuki coupling of compound (3) led to the synthesis of a library of derivatives <b>(4a-4f)</b>, which were obtained with yields varying from 56% to 71%. Subsequently, the synthesized molecules <b>(4a-4&#xa0;h)</b> were assessed for their antibacterial activity against clinically isolated NDM-β-lactamase (ST147). Further, In silico studies were carried out by using protein with the PDB ID: 5N5I, derived from NDM-KP (ST147). The chloro-substituted molecule <b>4e</b>, which shows potential as a drug candidate (MIC = 3.125&#xa0;µg/mL and MBC = 6.25&#xa0;µg/mL), displayed the highest level of effectiveness against resistant bacterial strains. Moreover, DFT calculations were employed to determine the frontier molecular orbitals, molecular electrostatic potential (MEP) maps, HOMO-LUMO energy values, hyperpolarizability, and reactivity descriptors for each compound. In this series, compound <b>4c</b>, where biphenyl is substituted with OCH<sub>3</sub>, exhibits the smallest energy gap of 4.24&#xa0;eV and 4.51&#xa0;eV, along with the highest hyperpolarizability values of 5495.62 Hatree. This compound, being the least stable, results in the most significant nonlinear optical (NLO) response. In the next phase of <i>the in vivo</i> experimental trial, the lead molecule could present an alternative therapeutic option.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Titanium-Mediated Synthesis and Pd-Catalyzed Derivatization of Thiophene Carboxylates: Antibacterial Evaluation Against NDM-β-Lactamase-Producing Klebsiella Pneumoniae (ST147)

  • 期刊论文

  • 发表日期：

    2025年10月28日

查看全文
  • Mujahad Abbas,
  • Maria Sohail,
  • Nasir Rasool,
  • Muhammad Usman Qamar,
  • Abid Mahmood,
  • Aqsa Kanwal,
  • Adeel Mubarik,
  • Shamoon Hassan,
  • Muhammad Imran,
  • Adnan Ali Shah

摘要

NDM-1-KP ST 147 remains a serious challenge in clinical practice, primarily due to its increasing resistance to carbapenems and its hypervirulent characteristics. A range of virulence factors is involved in this hypervirulence, and the mechanisms underlying carbapenem resistance are complex and multifaceted. The NDM KP (ST147) has emerged as a recent addition to the family of successful clones within the species. In this study, we synthesized methyl 3-(4-chlorobenzamido)-4-methylthiophene-2-carboxylate (3) by reacting amino thiophene (1) with 4-bromobenzoic acid (2) in the presence of TiCl4 (catalyst) and pyridine. The Suzuki coupling of compound (3) led to the synthesis of a library of derivatives (4a-4f), which were obtained with yields varying from 56% to 71%. Subsequently, the synthesized molecules (4a-4 h) were assessed for their antibacterial activity against clinically isolated NDM-β-lactamase (ST147). Further, In silico studies were carried out by using protein with the PDB ID: 5N5I, derived from NDM-KP (ST147). The chloro-substituted molecule 4e, which shows potential as a drug candidate (MIC = 3.125 µg/mL and MBC = 6.25 µg/mL), displayed the highest level of effectiveness against resistant bacterial strains. Moreover, DFT calculations were employed to determine the frontier molecular orbitals, molecular electrostatic potential (MEP) maps, HOMO-LUMO energy values, hyperpolarizability, and reactivity descriptors for each compound. In this series, compound 4c, where biphenyl is substituted with OCH3, exhibits the smallest energy gap of 4.24 eV and 4.51 eV, along with the highest hyperpolarizability values of 5495.62 Hatree. This compound, being the least stable, results in the most significant nonlinear optical (NLO) response. In the next phase of the in vivo experimental trial, the lead molecule could present an alternative therapeutic option.

Graphical Abstract