Recent studies on lonidamine, the lead compound of the antispermatogenic indazol-carboxylic acids.
Lonidamine (LND) or [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is an anticancer and an antispermatogenic drug whose mechanism of action is still incompletely understood. LND is effective against a number of tumors, including head, neck and breast cancers, probably because of the inhibition of mitochondrial electron transport and the enzyme hexokinase and to the induction of apoptosis. Instead, the antispermatogenic activity of LND appeared to be related not only to its energolytic activity but also to other effects activities such as the inhibition of specific chloride channels in the epididymis and the disruption of the inter-Sertoli-germ cell junctions, leading to premature release of germ cells. In addition, we recently reported that, in the rat, LND at the dose of 100 mg/Kg b.w. p.o., a fully active but well tolerated dose, caused specific changes of the testicular and epididymal macroglobulins (alpha(2)-macroglobulin, alpha(1) inhibitor-3 and alpha(1)-macroglobulin). Further studies are needed to elucidate the mechanism of action of LND, the lead compound of an interesting class of antispermatogenic drugs based on the core structure of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid.
Gatto
Maria Teresa
MT
Department of Pharmacology of Natural Substances and General Physiology, University of Rome La Sapienza, Italy.
Tita
Beatrice
B
Artico
Marco
M
Saso
Luciano
L
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000988:Antispermatogenic Agents / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D000970:Antineoplastic Agents; D000988:Antispermatogenic Agents; D007191:Indazoles; D011506:Proteins; D000511:alpha-Macroglobulins; C016371:lonidamine