Antimalarial structure

Chloroquine is the most effective of the hundreds of 4-aminoquinolines synthesized and tested during World War II as potential antimalarials. Structure-activity relationships demonstrated that the chloro at the 8-position increased activity, whereas alkylation at C-3 and C-8 diminished activity. The replacement of one of its N-ethyl groups with an hydroxyethyl produced... 

The antimalarial properties attributed to preparations from Dichroa febrifuga by the Chinese were confirmed about 1944 and two alkaloids, febrifugine (999) and isofebrifugine (1000), were isolated eventually. After difficult structural elucidations, syntheses of ( )-febrifugine followed it proved to be half as active as the natural material, itself far better than quinine, but the therapeutic index was disappointingly low (67HC(24-l)490). 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions... 

In the hydrolysis of acridine antimalarials, the role of the protonated species of the substrate appeared to be important even in aqueous solution buffered at pH 7.3, i.e., under conditions of physiological interest.Moreover, out of the three possible modes of reaction mathematically possible (H3O+-HB, HgO-f BH+, and OH -f BH2+, where B is the basic substrate) the one not involving the protonated substrate can be ruled out on structural grounds. 

The pioneering work carried out in Germany in the 1920s showed that appropriately substituted aminoquinolines and amino-acridines afforded a series of synthetic compounds that exhibited antimalarial activity.The exigencies of the Second World War led to a massive program aimed at the same goal in this country. This work led to the development of two distinct structural classes of quinoline antimalarials the 4-amino-7-chloroquino-... 

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. 

Fig. 14. X-ray crystal structure of [Ga(madd)]+ 80, a potential antimalarial agent. Adapted from (343).

Fig. 26. X-ray crystal structure of the Fe(III) complex of the antimalarial chelator desferrioxamine 108. Adapted from (542). 

A recent X-ray-crystallographic investigation [86) has provided the first accurate structural picture of a biguanide derivative, namely that of the antimalarial Paludrine (l-p-chlorophenyl-5-isopropyibiguanide hydrochloride) (Fig. 1). The biguanide part of the cation consists of two... 

CXXVI) may be rejected. Structure CXXVI is also inadmissible because the product cannot be reduced to l-p-chlorophenyl-5-isopropylbiguanide, and has no antimalarial properties. 

The structural diversity of natural products with antimalarial activity from marine and freshwater sources are stunning, ranging from isonitrile-containing derivatives to depsipeptides through peroxides and alkaloids. 

Mukherjee, P., Pradhan, A., Shah, F., Tekwanih, B.L. and Averya, M.A. (2008) Structural insights into the Plasmodium falciparum histone deacetylase 1 (PfHDAC-1) A novel target for the development of antimalarial therapy. Bioorganic and Medicinal Chemistry, 16, 5254-5265. 

The ozonide (176) was prepared as part of a synthetic study towards the antimalarial natural product artemisinin (177) <92JCS(Pl)325l>. It proved stable enough to allow x-ray crystal structure determination (see Section 4.16.3.1). Other, more complex, polycyclic ozonides were prepared in order to investigate possible antimalarial properties. Compounds were evaluated in vitro for antimalarial activity using a multiresistant strain of Plasmodium falciparum. Most were found to be weakly active although a thousand times less active than artemisinin. 

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