Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy against malaria. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. Artemethe involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Other mechanisms of action for artemether include their ability to reduce fever by production of signals to hypothalamus thermoregulatory center. Now, recent research has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the brain and spinal cord, which is selectively inhibited by artemether, and is distinct from the two already known cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain and spinal cord explains the ability of artemether in relieving pain and reducing fever which is produced by malaria. The most common adverse reactions in adults (>30%) are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. Proguanil in combination with atovaquone are marked under the brand name malarone, which is indicated for the treatment of acute, uncomplicated P. falciparum malaria and for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. Atovaquone and proguanil, interfere with 2 different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis. Recently were done experiments, which confirmed the hypothesis that proguanil might act on another target than dihydrofolate reductase. In addition, was made conclusion, that effectiveness of malarone was due to the synergism between atovaquone and proguanil and may not require the presence of cycloguanil.

Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward sodium current (INa). Quinidine's effect on INa is known as a 'use-dependent block'. This means at higher heart rates, the block increases, while at lower heart rates, the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the cardiac action potential to decrease (decreased Vmax). Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (ICA), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito. Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6 and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression if the two drugs are coadministered. Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes, so is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system and may lead to thrombocytic purpura. A combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis. This drug is marketed as Nuedexta in the United States. Intravenous quinidine is also indicated for the treatment of Plasmodium falciparum malaria. However, quinidine is not considered the first-line therapy for P. falciparum. The recommended treatments for P. falciparum malaria, according to the Toronto Notes 2008, are a combination of either quinine and doxycycline or atovaquone and proguanil (Malarone). The drug is also effective for the treatment of atrial fibrillation in horses.

Quinine soluble salts possess the extremely bitter taste, that may have a perplexing problem especially to children. That is why the most common combinations which are administered in this way are the sulphate, salicylate, tannate and certain esters. Quinine tannate, an insoluble quinine salt has been known in medicine for a very long time. However, many experiments have revealed that quinine tannate was practically inert as a medicinal substance.

Artefenomel, a novel trioxolane, is a lead candidate for inclusion in a new antimalarial combination, specifically formulated for children. Artefenomel has been demonstrated curative in as little as one dose.

Cycloheximide is an antibiotic produced by fermentation culture of Streptomyces griseus, Streptomyces noursei, Streptomyces albulus, Streptomyces naraensis, or other cycloheximide-producing microorganism. It was first discovered by A. Whiffen et al. in 1946. She observed the activity of the compound against the yeasts and it became known as the first antifungal antibiotic. Cycloheximide has been marketed as a plant fungicide for many years and this use continues mainly against fungal diseases of turf and for powdery mildew on roses. More recently, cycloheximide has been recognized and is being developed as an abscission agent for citrus fruits and olives. Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects, cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Cycloheximide is an antimitotic and an inhibitor of the synthesis of both DNA and protein.

Temefos (Diphos, Temephos) is an organophosphate larvicide, used to treat water infested with disease-carrying insects including mosquitoes, midges, and black fly larvae. Temefos affects the central nervous system through inhibition of cholinesterase, results in death before reaching the adult stage. Diphos has been used in trials studying the treatment of Plasmodium Falciparum Malaria. Temephos was first registered in the United States in 1965 by American Cyanamid Company for a number of uses including citrus fruits, pet collars, and mosquito control. A Registration Standard was issued in August, 1981. In response to EPA's 1991 Data Call-In, American Cyanamid dropped all uses except the mosquito larvicide use in non-potable waters and requested a low volume minor use waiver for relief from the data requirements associated with that use.

MDL-201053, (DL-ALANINE)- (Z-FA-FMK) is an irreversible inhibitor of cysteine proteases, such as cathepsin B, L, and S. The compound has also inhibitited papain and cruzain. Z-FA-FMK has been shown to selectively inhibit effector caspase-2, caspase-3, caspase-6, and caspase-7 without affecting initiator caspase-8 and caspase-10 while showing minimal toxicity to normal mammalian cells in vitro. Due to Z-FA-FMK's effector caspase specificity, the compound has been recorded to inhibit some forms of caspase mediated apoptosis. The compound has been observed to be an effective in time dependent inactivation of cathepsin B isozymes from a number of tissues. Studies show Cathepsin B-like activity plays a role in the cascade of proteolytic cartilage destruction. Z-FA-FMK is an inhibitor of cathepsin H. This compound has been shown to block the production of IL1-α, IL1-β, and TNF-α induced by LPS in macrophages by inhibiting NF-κB pathways. Z-FA-FMK blocks not only NF-kappaB activation but inhibits, also, T cell blast formation, and prevents cells from entering and leaving the cell cycle revealing demonstrating immunosuppressive abilities. Z-FA-FMK is a very effective viral inhibitor that can prevent reovirus replication in vitro and reovirus-mediated myocarditis, as well as reovirus-mediated oncolysis, in vivo.

Rutarin is a coumarin glycoside. Rutarin is found in herbs and spices. Rutarin has antibiotic activity. Rutarin inhibited Plasmodium falciparum with IC50 value of 88 ug/mL.