Antischistosomal activity

Reduction of the heterocyclic ring and incorporation of a nitro function affords a compound with antischistosomal activity, oxamniquine (60). Its synthesis begins with chlorination of 2,6-dimethyl-quinoline, which proceeds regiospecifically on the methyl group adjacent to the ring nitrogen (56). 

Antischistosomal activity. Hot water extract of the dried rhizome, taken orally by human adults at variable dosage levels, was active. A mixture of Rehmannia glutinosa (Rt), Dioscorea batatas (Tu), Dolichos lablab (Sd), Glycyrrhiza uralensis (Rt), Zingiber officinale (Rh), Evodiarutae carpa (Fr), Atractylodes macrocephala (Rh), and Panax ginseng (Rt) was used . ... 

Antischistosomal activity, of 5-nitro-2-aminothiazoles, 72 Antispasmodic activity, 150, 439 Antitrichomonal activity, 138 of 5-nitro-2-aminothiazoles, 72 Antitubercular activity, 139, 140,441,442 Antitumor activity, 149, 152 Antitussive, 144, 148 Antiulcer properties, 148 Antiviral, 138, 139, 140, 144,438 Appetite depressant, 147 Aprotic solvent, see Solvent effect Aromatic aldehydes, with aminothiazoles, 40... 

Mjrrh is an oleo gum resin obtained from the stem of Commiphora molmol, a tree that grows in north-east Africa and the Arabian Peninsula. In mice, myrrh showed no mutagenic effects and was a potent cytotoxic drug against solid tumor cells (5). The antitumor potential of C. molmol was comparable to that of cyclophosphamide. Studies in hamsters suggested an antischistosomal activity of myrrh (6). 

It has been suggested that inhibition of PFK activity and subsequent depletion of energy in the parasites may not fully account for the antischistosomal activity of the antimonials [99]. Work carried out in this direction indicates that the antimonials might induce lesions on the fluke s tegument. This tegumental disruption could expose the "hidden" antigens of the parasite making it susceptible to the attack by the host s immune system [100-102]. 

Some 5-nitro-l,2-disubstituted-imidazoles of the type 11 and 12 have been shown to have appreciable in vitro and in vivo antischistosomal activities, but none find use in clinical practice [21]. However, metronidazole (13) has been used widely to treat guinea worm (Dracunculus medineusis) infection in human [22]. 

In 1955, Cuckler and coworkers [23] demonstrated the antischistosomal activity of 2-acetamido-5-nitrothiazole (14) this compound was found to be marginally effective in reducing the schistosome population when given at a concentration of 0.1-0.4% in diet. A major breakthrough was achieved when Ciba laboratories undertook an extensive search for potential antibacterial and/or antiparasitic agents derived from nitroheterocycles. In 1964, Lambert et al. [24,25] announced the discovery of niridazole (15) as a novel drug for the treatment of schistosomiasis. 

The discovery of the anthelmintic activity of the pyrazinoisoquinolines [25,31,32] initiated the synthesis of a variety of substituted pyrazinoisoquinolines. Praziquantel was picked up from more than 400 l,2,3,6,7,llb-hexahydro-4H-pyraz-ino[2,l-a]isoquinolin-4-ones and related compounds, because of its potent and broad spectrum biological activity [26]. The structure activity relationship in the analogues of praziquantel would indicate that positions 2 and 4 are the most critical positions, which govern the cestodicidal as well as antischistosomal activities in the pyrazinoisoquinolines. 

The exact mode of action of oxamniquine is unknown [83]. The drug exhibits anticholinergic action its action on neuromuscular transmission has been demonstrated [119]. It has been suggested that oxamniquine (14) is converted enzymatically into a phosphate or sulphate ester (50), which then dissociates non-enzymatically to form the chemically reactive species 51. This intermediate then alkylates essential macromolecules of the schistosomes like DNA to give a Drug-DNA complex (52) (Scheme 5) [1,120,121]. The antischistosomal activity of oxamniquine is due to its ability to alkylate DNA. It does not intercalate with DNA, because the drug molecule is not planar, an essential structural requirement for intercalation. The lower mutagenic property of oxamniquine may, therefore, be due to the fact that it is not a DNA inter-calator [1],... 

The antischistosomal activity of hycanthone is believed to be due to its ability to bind covalently with DNA by a reaction sequence very similar to that described for oxamniquine (Chapter 11). Lucanthone (25) is oxidized in the biophase to form hycanthone (26), which is transformed into the ester (85) in the presence of kinase or sulphotransferase. Non-enzymatic dissociation of 85 gives 86, which alkylates DNA to form the hycanthone-DNA complex (87). 

Some quassinoids isolated from the leaves of Evrycoma longifotia Jack, were subjected to in vitro antischistosomal activities [109],... 

The antischistosome activity of nitrofuran compounds was further investigated. Comparison of 3-(5-nitro-2-furyl)-substituted derivatives of propionic, acrylic and propiolic acids showed that a vinyl group is necessary for activity.1 5 in derivatives of 3-(5-nitro-2-furyl) acrylic acid, the 5-nitro group was required for activity.12 In a group of (5-nitro-2-furyl)-vinyl heterocycles containing a weakly basic N in a specific position, both the vinyl group and the N were essential for antischistosome activity.1 ... 

The structure-antischistosomal activity relationship and retinotoxic effects of several series of nuclear substituted aminophenoxyalkanes... 

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