Scholarlink

<p>Malaria is the extensive health concern in sub-Saharan Africa, with <i>Plasmodium falciparum</i> being the most lethal strain. The continued emergence of drug-resistant <i>P. falciparum</i> advocates for the development of new antimalarials. Our current study aimed to effectively explore the interaction capabilities of iso-mukaadial acetate (IMA) and betulinic acid (BA) against two essential <i>P. falciparum</i> glycolytic pathway proteins, PfLDH and PfHk. Recombinant PfLDH and PfHk were independently expressed in <i>E. coli</i> BL21 (DE3) cells and subsequently purified using affinity chromatography. Protein–ligand interaction studies probed in silico and in vitro approaches. Parasite inhibition studies confirmed potent antimalarial activity against the <i>P. falciparum</i> NF54 strains, with BA and IMA showing IC<sub>50</sub> values of 1.27&#xa0;µg/ml and 1.03&#xa0;µg/ml against the asexual stage of <i>P. falciparum</i>, respectively. FTIR experiments confirmed interactions between the compounds and the secondary structure of the proteins. Direct protein–ligand interaction studies analysis using microscale thermophoresis (MST) showed a K<sub>D</sub> value of 0.1036 ± 0.6001&#xa0;µM for the PfLDH-BA complex and 0.7473 ± 0.3554&#xa0;µM K<sub>D</sub> value for PfLDH-IMA. Meanwhile, PfHk-IMA had 0.39701 ± 0.16298&#xa0;µM K<sub>D</sub> value, while the PfHk-BA complex had no interaction detected. Molecular docking and molecular dynamics simulation studies were used to measure and confirm the interactive strength of complexes. Molecular docking reported a binding score of − 1.155&#xa0;kcal/mol for the PfLDH-BA complex and a binding score of − 3.200&#xa0;kcal/mol for PfLDH-IMA. The PfHk-BA complex had − 2.871&#xa0;kcal/mol and PfHk-IMA complex had − 4.225&#xa0;kcal/mol binding score. In conclusion, BA and IMA compounds had better interactions and remained bound within the binding sites of the glycolytic pathway proteins (PfLDH and PfHk).</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

Assessing the efficacy of iso-mukaadial acetate and betulinic acid against selected Plasmodium falciparum glycolytic pathway proteins: in silico and in vitro studies

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月18日

查看全文
  • Lindiwe Khumbuzile Zuma,
  • Ofentse Jacob Pooe,
  • Nonduduzo Hlengiwe Mabaso,
  • John Alake,
  • Vincent A. Obakachi,
  • Sinethemba Yakobi,
  • Nothando Gasa,
  • Rajshekhar Karpoormath,
  • Mthokozisi Simelane

摘要

Malaria is the extensive health concern in sub-Saharan Africa, with Plasmodium falciparum being the most lethal strain. The continued emergence of drug-resistant P. falciparum advocates for the development of new antimalarials. Our current study aimed to effectively explore the interaction capabilities of iso-mukaadial acetate (IMA) and betulinic acid (BA) against two essential P. falciparum glycolytic pathway proteins, PfLDH and PfHk. Recombinant PfLDH and PfHk were independently expressed in E. coli BL21 (DE3) cells and subsequently purified using affinity chromatography. Protein–ligand interaction studies probed in silico and in vitro approaches. Parasite inhibition studies confirmed potent antimalarial activity against the P. falciparum NF54 strains, with BA and IMA showing IC50 values of 1.27 µg/ml and 1.03 µg/ml against the asexual stage of P. falciparum, respectively. FTIR experiments confirmed interactions between the compounds and the secondary structure of the proteins. Direct protein–ligand interaction studies analysis using microscale thermophoresis (MST) showed a KD value of 0.1036 ± 0.6001 µM for the PfLDH-BA complex and 0.7473 ± 0.3554 µM KD value for PfLDH-IMA. Meanwhile, PfHk-IMA had 0.39701 ± 0.16298 µM KD value, while the PfHk-BA complex had no interaction detected. Molecular docking and molecular dynamics simulation studies were used to measure and confirm the interactive strength of complexes. Molecular docking reported a binding score of − 1.155 kcal/mol for the PfLDH-BA complex and a binding score of − 3.200 kcal/mol for PfLDH-IMA. The PfHk-BA complex had − 2.871 kcal/mol and PfHk-IMA complex had − 4.225 kcal/mol binding score. In conclusion, BA and IMA compounds had better interactions and remained bound within the binding sites of the glycolytic pathway proteins (PfLDH and PfHk).