1-(2-4-dichlorobenzyl)indazole-3-carbohydrazide and thiazolyl-blue

AbstractInhibition of sperm motility has recently become a promising target for male contraceptive development. AF-2364, an analogue of Lonidamine (LND), had a contraceptive effect when orally administered to adult Sprague-Dawley rats. LND can also target mitochondria to inhibit oxygen consumption and block energy metabolism in tumour cells. However, there are no reports of the effects of AF-2364 on human sperm function. Herein we describe the action of AF-2364 on human sperm in vitro, as well as the mechanisms involved. AF-2364 specifically blocked human sperm motility in vitro. Further experiments revealed that AF-2364 can target sperm mitochondrial permeability transition (MPT) pores to induce the loss of sperm mitochondrial membrane potential (DeltaPsim) and decrease ATP generation; however, no significant changes in the cytoskeletal network or the human sperm proteome were detected after exposure to AF-2364. Incubation of AF-2364 with other human or mouse cell lines indicated that the spermicidal effect at the lower concentration was specific. In summary, the spermicidal effect of AF-2364 involves direct action on sperm MPT pores, and this compound should be further investigated as a new spermicide candidate.

Topics: Adenosine Triphosphate; Animals; Cell Line, Tumor; Cell Survival; Cyclosporine; Drug Therapy, Combination; Humans; Hydrazines; Indazoles; Male; Mice; Mitochondria; Permeability; Seminal Plasma Proteins; Sperm Motility; Spermatocidal Agents; Spermatozoa; Tetrazolium Salts; Thiazoles