Natural products: a continuing source of novel drug leads.

The herb Artemisia annua has been used for many centuries in Chinese traditional medicine as a treatment for fever and malaria. In 1971, Chinese chemists isolated from the leafy portions of the plant the substance responsible for its reputed medicinal action. This compound, called qinghaosu (QHS, artemisinin), is a sesquiterpene lactone that bears a peroxide grouping and, unlike most other antimalarials, lacks a nitrogen-containing heterocyclic ring system. The compound has been used successfully in several thousand malaria patients in China, including those with both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Derivatives of QHS, such as dihydroqinghaosu, artemether, and the water-soluble sodium artesunate, appear to be more potent than QHS itself. Sodium artesunate acts rapidly in restoring to consciousness comatose patients with cerebral malaria. Thus QHS and its derivatives offer promise as a totally new class of antimalarials.

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Qinghaosu (artemisinin): an antimalarial drug from China

https://cyberleninka.org/article/n/132565.pdf

Discovery and resupply of pharmacologically active plant-derived natural products: A review.

4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Trimetazidine is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies. 4.2 Posology and method of administration Oral administration. Posology The dose is one tablet of 35mg of trimetazidine twice daily during meals. Special populations Renal impairment In patients with moderate renal impairment (creatinine clearance [30-60] ml/min) (see sections 4.4 and 5.2), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Elderly Elderly patients may have increased trimetazidine exposure due to age-related decrease in renal function (see section 5.2). In patients with moderate renal impairment (creatinine clearance [30-60] ml/min), the recommended dose is 1 tablet of 35mg in the morning during breakfast. Dose titration in elderly patients should be exercised with caution (see section 4.4). Health Products Regulatory Authority

Summary of product characteristics

The organoselenium and organotellurium compounds have been described as promising pharmacological agents in view of their unique biological properties. Glutathione peroxidase mimic, antioxidant activity and thioredoxin reductase inhibition are some of the properties reviewed here. On the other hand, little is known about the molecular toxicological effects of organoselenium and organotellurium compounds. Most of our knowledge arose from research on inorganic selenium and tellurium. However, the ability to oxidize sulfhydryl groups from biological molecules can be involved both in their pharmacological properties and in their toxicological effects. In fact, exposition to high doses of organoselenium or to low doses of organotellurium causes the depletion of endogenous reduced glutathione in a variety of tissues. Thus, the design of compounds that cause low depletion of glutathione and react with specific targeted proteins, controlling specific metabolic pathways, will represent an important progress in understanding the field of organochalcogen compounds. Furthermore, the development of new organochalcogens with higher thiol-peroxidase activity that can use other non-toxic thiol reducing agents, such as N-acetylcysteine instead of glutathione, will permit the investigation of the co-administration of organochalcogens and thiols as a formulation for antioxidant therapy.

Organoselenium and Organotellurium Compounds: Toxicology and Pharmacology

Reaction of selenium with sodium borohydride in protic solvents. A Facile Method for the introduction of selenium into organic molecules

Based on the antimalarial properties observed for 2-acetylpyridine 4-phenyl-3-thiosemicarbazone (1), an extensive series of related thiosemicarbazones was prepared and tested against Plasmodium berghei in mice. Screening results indicated that the presence of the 2-pyridylethylidene group was critical and that certain phenyl, benzyl, phenethyl, or cycloalkyl groups at N4 of the thiosemicarbazone moiety also contribute to antimalarial activity.

2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents

Reaction of the 2-acetylpyridine thiosemicarbazones, 3-azabicyclo[3.2.2]nonane-3-thiocarboxylic acid 2-[1-(2-pyridyl)ethylidene]hydrazide (IIIa), its selenium analogue (IIIb), 1H-hexahydroazepine-1-thiocarboxylic acid 2-[1-(2-pyridyl)ethylidene]hydrazide (IV), and 1H-octahydroazocine-1-thiocarboxylic acid 2-[1-(2-pyridyl)ethylidene]hydrazide (V) with Cu(II), Ni(II), Fe(III), and Mn(II) salts gave crystalline complexes. Relative to the free ligands, these complexes show reduced antimalarial activity in mice infected with Plasmodium berghei; however, antileukemic properties are enhanced by coordination with the above-mentioned metals.

Daniel L. Klayman

Papers

Qinghaosu (artemisinin): an antimalarial drug from China

Reaction of selenium with sodium borohydride in protic solvents. A Facile Method for the introduction of selenium into organic molecules

2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents

2-Acetylpyridine thiosemicarbazones. 4. Complexes with transition metals as antimalarial and antileukemic agents.

Isolation of artemisinin (qinghaosu) from Artemisia annua growing in the United States.