Abstract
The emergence of artemisinin resistance could adversely impact the current strategy for malaria treatment; thus, new drugs are urgently needed. A possible approach to developing new antimalarials is to find new uses for old drugs. Some anticancer agents such as methotrexate and trimetrexate are active against malaria. However, they are commonly perceived to be toxic and thus not suitable for malaria treatment. In this opinion article, we examine how the toxicity of anticancer agents is just a matter of dose or ‘only dose makes the poison’, as coined in Paracelsus’ law. Thus, the opportunity exists to discover new antimalarials using the anticancer pharmacopoeia.
Highlights
The need for new antimalarial drugs The malaria parasite, the cause of one of the most significant infectious diseases, is characterised by an intrinsic ability to select for resistance against drugs
We examine how the toxicity of anticancer agents is just a matter of dose or ‘only dose makes the poison’, as coined in Paracelsus’ law
Other anticancer drugs in the treatment of malaria and other non-neoplastic diseases We have shown that the folate antagonist pemetrexate is active against P. falciparum in vitro, with activity in the nanomolar range (IC50
Summary
200–2000 mg per dose ALL, breast cancer, head and neck cancer, NHL, lung cancer, osteosarcoma, Trophoblastic neoplasm. Grade 3 Neurological, gastrointestinal and dermatological symptoms. 7.5–35 mg per week Crohn’s disease, rheumatoid arthritis, JIA, psoriasis, psoriatic arthritis. Grade 0–1 Gastrointestinal symptoms, transient elevation of liver enzymes, liver dysfunction [19,20,22]. 250–1300 mg per dose ALL, breast cancer, Burkitt lymphoma, HD, NHL, MM, ovarian cancer, retinoblastoma. Grade 3 Gastrointestinal, dermatological and catarrhal symptoms. Gastrointestinal, pulmonary fibrosis, ITP, JIA, lupus catarrhal and dermatological nephritis, NS, SLE, transplant symptoms rejection prophylaxis, multiple sclerosis, Wegener’s granulomatosis. 6-Mercapto-purine Purine antagonist, inhibitor 150–350 mg per dose of DNA and RNA synthesis ALL, AML, CML
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