Antimalarial drugs structure

The in vivo antitumor and trypanocidal effects of dimeric [Irn2(CH3COO)4(L)ra]° (L = classical organic antimalarial drugs, n= 1, 2) are reported.494 The dimeric complexes are characterized by IR spectroscopy. Further studies of monomeric Ir11 complexes, IrnL2, where L = alkyl or aryl dithiocarbamates and xanthates, reveal no clear relation between antitumor and antitrypanosomal actvities.495 Structure-activity data for the Ir11 complexes is presented. 

Copyright The McGraw-Hill Companies, Inc. All rights reserved. Structural formulas of antimalarial drugs. 

Despite these significant advances and an overall pattern of clinical acceptability and low toxicity in animals, recent studies of arteether 6 have uncovered an unsettling neurotoxicity in animals leading to death at higher than therapeutic doses.9,10 This toxicity, a lethal degeneration of the brain stem, has resulted in a reexamination of these antimalarial drugs, particularly structure-activity relationships (SAR) as directed toward potency, oral administration, and neurotoxicity. 

In order to examine SARs in this mechanistically and structurally novel antimalarial drug class, and to make a comparison with structure-toxicity relationships, we established a convenient synthesis of the natural product.21 Making liberal use of a key synthetic intermediate from this synthesis has provided entry to a variety of analog classes, as well as radiolabeled artemisinin22 (Figure 9.5). 

Asawamahasakda, W., Ittarat, I., Pu, Y.-M., Ziffer, H., and Meshnick, S.R. Reaction of antimalarial endoperoxides with specific parasite proteins, Antimicrob. Agents Chemother., 38, 1854, 1994 Yang, Y.-Z., Little, B., and Meshnick, R. Alkylation of proteins by artemisinin effects of heme, pH, and drug structure, Biochem. Pharmacol., 48, 569,1994. 

Muscle. Binding of drugs to components within the muscle may create the long-term storage of these compounds. Various agents may be actively transported into the muscle cell and may form reversible bonds to intracellular structures such as proteins, nucleoproteins, or phospholipids. An example is the antimalarial drug quinacrine. 

US Army Survey An extensive collection of antimalarial-drug animal SAR data, including structures, bioactivity, etc., published originally by the US Army in 1946. 12,318... 

Numerous in silico studies have been undertaken with the focus of identifying or developing novel antimalarial drugs as well as understanding the structure-activity relationships (SARs) for sets of... 

Some nontaxoid MDR reversal compounds may share common structure features with the above-mentioned MDR reversal taxoids. For example, Chibale et al. attached hydrophobic moities to the antimalarial drugs chloroquine and primaquine, and they found that chloroquine derivatives are superior to primaquine derivatives against MDR in vitro and in vivo when coinjected with paclitaxel. Unexpectedly, they observed that those chloroquines fit very well to two baccatin Ill-based MDR reversal compounds in silico. " ... 

In view of the known basic antimalarial drugs (such as chloroquine, quinine) that are being used as salts for injection, it was proposed that introducing an amino group into the qinghaosu molecule may lead to water-soluble derivatives. Thus, five types of basic qinghaosu derivatives were synthesized (Structure... 

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