Anti-malarial agents

Quinazoline alkaloids are known as biologically active compounds. Arborine inhibits the peripheral action of acetylcholine and induces a fall in blood pressure. Febrifugine is an anti-malarial agent and vasicine acts as a uterine stimulant. Glomerin and homoglomerin are alkaloids of the defensive system in some organisms (e.g., in the glomerid millipede). 

Hemolytic anemia can be caused by eating foods (such as fava beans) or taking drugs (such as anti-malarial agents or acetaminophen) that have oxidizing properties. 

Quinidine. Derived from cinchona (anti- bark (minor alkaloid), the anti-malarial agent quinine being a major alkaloid... 

Balint, G.A. (2001) Artemisinin and its derivatives an important new class of anti-malarial agents. Pharmacol. Ther., 90, 261-5. 

Quinine (5) isolated from Cinchona bark was one of the hrst antimalarials discovered, and it became a model for the discovery and development of some of the most successful anti-malarial agents, chloroquine and its successors. However, the... 

Quinoline-containing 1,2,4-trioxolanes such as 107 have been patented as anti-malarial agents <05FRP2862304>. Further results on the reactivity of the novel 13,2-dioxathiolane-2-thione containing the cyclic thionosulfite function have appeared <05HCA1451> and a convenient method for direct conversion of 1,2-diols into cyclic sulfates using sulfuryl chloride has been described <05TA3908>. 

In search of potential anti-malarial agents, Dobson et al. (48JCS123) prepared 7,10-dichlorobenzo[ ][l,7]phenanthroline 52 by the route described in Scheme 1, but with 5-aminoquinoline 48 as a precursor of... 

MODEL SYSTEMS FOR THE DISCOVERY AND EVALUATION OF POTENTIAL ANTI-MALARIAL AGENTS... 

The mechanism of action of the immunological and anti-inflammatory effects of antimalarials include inhibition of phospholipase A, inhibition of platelet aggregation, a range of lysosomal effects (e.g., an increase in pH, membrane stabilization, and inhibition of release and activity of lysosomal enzymes), inhibition of phagocytosis, an increase in intracellular pH in cytoplasmic vacuoles leading to decreased stimulation of autoimmune CD4 T cells, decreased cytokine release from lymphocytes and stimulated monocytes, inhibition of immune complex formation, and antioxidant activity. In patients with porphyria cutanea tarda, chloroquine and hydroxychloroquine bind to porphyrins and/or iron to facilitate their hepatic clearance. The ability to bind to melanin and other pigments may contribute to the retinal toxicity seen occasionally when anti-malarial agents are used. 

It is used in the manufacture of dyes, pharmaceuticals, and insecticides, and as an anti-malarial agent. 

Chong, C.R., et al. A clinical drug library screen identifies astemizole as an anti-malarial agent. Nat. Chem. Biol. 2006, 2, 415 16. 

C-10 pyrrole Mannich bases of artemisinin have been aceessed as potential anti-malarial agents. Treatment of dihydroartemisinin with N-methylpyrrole in the presence of a Lewis acid gave rise to the C-10 pyrrole analogue. The subsequent Mannich reaction used preformed Eschenmoser s salt to afford the dimethylaminopyrrole, which was an anti-malarial with enhanced water solubility. 

On the other hand, Mannich reaction of 5-chloro-8-hydroxy quinoline with formaldehyde and A //-diethylpropylenediamine proceeds according to the expected 7-substitution based on the prior substitution of positions C5 and C8 in a 5,8-disubstituted quinoline to afford the anti-malarial agent clamoxyquin. ... 

Oxidative cyclizations are generally facilitated by the use of Pd(OAc)2 in acetic acid under reflux. The initial step in these oxidative cyclization reactions is believed to be the electrophilic palladation of the aromatic ring. An example is presented in the preparation of anti-malarial agent quindoline, isolated from a West African plant Cryptolepis sanguinolenta, which was synthesized through an oxidative cyclization of the appropriately 3-substituted quinoline in the presence of two equivalents of Pd(OAc)2 in trifluoroacetic acid. ... 

Theeraladanon C, Arisawa M, Nishida A, Nakagawa M (2004) A novel synthesis of substituted quinolines using ring-closing metathesis (RCM) its application to the synthesis of key intermediates for anti-malarial agents. Tetrahedron 60 3017-3035... 

The structures of two antiarrhythmic agents, quinidine, a natural product, and disopyramide (Searle Roussel, 1972) are shown in Figure 4.2. Quinidine was first isolated from cinchona bark but is now made by the epimerization of quinine at the carbon bearing the hydroxyl group. Its effects on arrhythmias were first noted more than 200 years ago when the drug was being used as an anti-malarial agent. 

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