Gefitinib as an antimalarial: unveiling its therapeutic potential.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-02-28 DOI:10.1007/s10787-025-01682-5

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

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引用次数: 0

Abstract

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.

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]