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<p>Resistant strains of <i>Plasmodium</i> spp. pose a great threat to healthcare. Drug repurposing is a smart, and an effective way to look for new alternatives for different ailments including malaria. Protein tyrosine kinases (PTKs) play a crucial role in growth, maturation as well as differentiation of <i>Plasmodium</i> and this study explores antimalarial activity of PTKs inhibitor gefitinib using in silico and experimental approaches. The drug showed considerable inhibitory activity against <i>P. falciparum</i> 3D7 (IC<sub>50</sub> 0.49&#xa0;µg/mL) and RKL-9 (IC<sub>50</sub> 0.83&#xa0;µg/mL) strains. Isobologram analysis revealed substantial synergism between gefitinib and artesunate. Gefitinib illustrated highest negative D-score towards phosphoethanolamine methyltransferase followed by <i>Pf</i>PK5 and CDPK1. Its acute toxicity was 4&#xa0;g/kg. Gefitinib (100&#xa0;mg/kg) exhibited a dose-dependent curative activity against <i>P. berghei</i> with 91.09% chemo-suppression and the combination of gefitinib 100&#xa0;mg/kg and AS 50&#xa0;mg/kg exhibited complete parasite clearance with no recrudescence which was also evidenced by cytokine analysis, biochemical as well as histopathological studies. At length, gefitinib illustrated considerable antiplasmodial action by targeting phosphoethanolamine methyltransferase, <i>Pf</i>PK5 and CDPK1. The combination of gefitinib (100&#xa0;mg/kg) and AS (50&#xa0;mg/kg) holds promise for malaria treatment. Further, research is being done to evaluate its pharmacokinetic properties.</p>

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Gefitinib as an antimalarial: unveiling its therapeutic potential

  • 期刊论文

  • 发表日期：

    2025年2月28日

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  • Varun Gorki,
  • Neha Sylvia Walter,
  • Monika Chauhan,
  • Neelima Dhingra,
  • Upma Bagai,
  • Sukhbir Kaur

摘要

Resistant strains of Plasmodium spp. pose a great threat to healthcare. Drug repurposing is a smart, and an effective way to look for new alternatives for different ailments including malaria. Protein tyrosine kinases (PTKs) play a crucial role in growth, maturation as well as differentiation of Plasmodium and this study explores antimalarial activity of PTKs inhibitor gefitinib using in silico and experimental approaches. The drug showed considerable inhibitory activity against P. falciparum 3D7 (IC50 0.49 µg/mL) and RKL-9 (IC50 0.83 µg/mL) strains. Isobologram analysis revealed substantial synergism between gefitinib and artesunate. Gefitinib illustrated highest negative D-score towards phosphoethanolamine methyltransferase followed by PfPK5 and CDPK1. Its acute toxicity was 4 g/kg. Gefitinib (100 mg/kg) exhibited a dose-dependent curative activity against P. berghei with 91.09% chemo-suppression and the combination of gefitinib 100 mg/kg and AS 50 mg/kg exhibited complete parasite clearance with no recrudescence which was also evidenced by cytokine analysis, biochemical as well as histopathological studies. At length, gefitinib illustrated considerable antiplasmodial action by targeting phosphoethanolamine methyltransferase, PfPK5 and CDPK1. The combination of gefitinib (100 mg/kg) and AS (50 mg/kg) holds promise for malaria treatment. Further, research is being done to evaluate its pharmacokinetic properties.