Lucanthone

It was subsequently discovered that lucanthone is metabolized in the body in part to hycanthone (30), a compound with enhanced schistomacidal activity. The relatively high biologic activity of lucanthone in experimental animals compared to man was subsequently attributed to the inefficient hydroxylating system present in man for this biochemical conversion.Microbiologic oxidation of lucanthone by fermentation with the fungus Aspergil-lus scelorotium affords hycanthone. ... 

Lucanthone (20) constitutes one of the first effective antischistosomal agents. Biological investigation of this agent showed that the active species in man is in fact the hydroxylated metabolic product hycanthone (21). The published Synthesis for the... 

The two most active compounds in this series are 5-[4-(2-diethylaminoethyl-amino)-l-naphthylazo] uracil (XLa) and 5-(4-amino-l-naphthylazo)uracil (XLb), (ANU). In mice infected with the Puerto Rican strain of S. mansoni, compound (XLa) causes an 82—100 per cent reduction in live worms when administered in the diet at 167—489 mg/kg per day for 14 days [334], whereas ANU (XLb) causes a 73—100 per cent reduction at 221—804 mg/kg per day for the same period [335]. These compounds are reported to be more effective than either lucanthone hydrochloride [334, 336] or the tris-(p-aminophenyl)carbonium salts [334—337]. Substitution of the amino groups at other positions in the... 

Leffler Freytag reaction, 338 Leprosy, 139 Levallorphan, 293 Levarteronol, 63 Levolorphanol, 296 Levonordefrine, 68 Levophenacylmorphan, 294 Levopropoxyphene, 50 Levorphanol, 293 Levothyroxine, 97 Librium , 365 Lidocaine, 16 Lidoflazine, 279 Liothyronine, 97 Lipid-water partition, 3, 21 Lipophilicity, 213 Lorazepam, 368 Lucanthone, 397 Lumisterol, 184 Lyndiol , 186... 

Lobendazole, 353 Lometraline, 214 Lomustine, 12, 15 Loperamide, 334 Lorbamate, 21 Loxapine, 427 LSD-25, 476 Lucanthone, 413 Luteolytic activity, 6 Lysergic acid, 475... 

Intercalation has been demonstrated with a number of other compounds having a polycyclic aromatic system and groups capable of forming hydrogen bonds. Among such compounds are the antibacterial 9-aminoacridine, the antimalarials mepacrine and chloroquine, the veterinary trypanocide ethidium (246), the thioxanthone lucanthone (247 R = Me) and its more active metabolite hycanthone (247 R = CH20H), which are used in the treatment of schistosomiasis, and the antineoplastic alkaloid ellipticine (248). A number of antibiotics, including the actinomycins, echinomycin and bleomycin, also intercalate. 

The excellent antitumor activity of ellipticine carbamate 153 led Archer and co-workers (84) to propose a new mechanism for the antitumor effects of ellipticine in general (Scheme 65). It is suggested that the C-5 methyl group is enzymatically hydroxylated and then converted either to the sulfate (402) or phosphate ester. This can now react with a cellular nucleophile (e.g., DNA, topoisomerase II), by an S l or 8 2 mechanism, to give the covalent adduct 403. This type of mechanism has been invoked to explain the antitumor activity of lucanthone (404) and hycanthone (405) (219,220). A study of the azaellip-ticines 204 and 406 showed that both compounds are active on topoisomerase II and initiate the cleavage of DNA (151,221). However, unlike ellipticine, these azaellipticines did not cleave DNA in isolated nuclei. 

S YNS 1 -((2-(DlETHYLAMINO)ETHYL)AMINO)-4-METHYL-9H-THIOXANTHEN-9-ONE LUCANTHON LUCANTHONE MIRACIL D NILODIN... 

C20H24N202S lucanthone metabolite 3105-97-3 25.00 1 1581 2 32386 C20H32O2 androstane-17-carboxylic acid. (5beta,l7beta) 438-08-4 20.00 0.9151 2... 

Hycanthone is a derivative of lucanthone, but has less gastrointestinal and nervous system toxicity. It is effective against both Schistosoma hematobium and Schistosoma mansoni and is given as a single intramuscular injection in doses of 1.0-2.5 mg/kg (1,2). However, it has largely been superseded in the treatment of schistosomiasis by more recent, less toxic compounds. The most common adverse reactions to hycanthone, which occur in up to... 

The first stage in the development of oxamniquine was to find a lead compound, and so a study was made of compounds which were active against the parasite. The tricyclic structure lucanthone (Fig. 7.32) was chosen. It was known to be effective against some forms of the disease, but it was also toxic and had to be injected at regular intervals to remain effective. Therefore, the goal was to increase the activity of the drug, broaden its activity, reduce side-effects, and make it orally active. 

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