ABSTRACT
S,S'-[disulfanediylbis(dialkylaminopropane-2,1-diyl)]bis- (dialkylaminothiocarbamate) (14-31) were prepared and evaluated for the spermicidal activity and antifungal activity. Dialkyldithiocarbamates (1-5) were reacted with epichlorohydrin to give 1-dialkylaminocarbothioic acid S-[(2,3-epithio)propyl]ester (7-11), these on further reaction with a secondary amine gave S,S'-[disulfanediylbis(dialkylaminopropane-2,1-diyl)]bis- (dialkylaminothiocarbamate) (14-31). Some of these compounds (16, 19-21, 23, 30, 31) were found to be very potent spermicidal agents with marginal antifungal activity. Two compounds (20, 21) were 25 times more active than nonoxynol-9 (N-9), the spermicide currently in the market.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Disulfides/chemistry , Disulfides/pharmacology , Ethylamines/chemistry , Semen/drug effects , Spermatocidal Agents/chemistry , Spermatocidal Agents/pharmacology , Sulfhydryl Compounds/chemistry , Antifungal Agents/chemical synthesis , Disulfides/chemical synthesis , Humans , Male , Sperm Count , Sperm Motility/drug effects , Spermatocidal Agents/chemical synthesisABSTRACT
OBJECTIVE: To examine the role of Sertoli cells in the antispermatogenic action of two nonsteroidal male contraceptive compounds (CDRI-84/35 and gossypol) by evaluating their effect on some key parameters of Sertoli cell function in vitro. METHODS: Primary cultures of Sertoli cell were established from 18-day-old rat testis and treated on day 5 with different concentrations (1.0, 0.1, 0.01, and 0.001 mM) of either CDRI-84/35 or gossypol in vitro. Lactate (secretion), along with beta-glucuronidase, gamma-glutamyl transpeptidase, lactate dehydrogenase (LDH) and aromatase activities, was measured in these cells to examine the functions targeted by antispermatogenic agents in Sertoli cells. RESULTS: CDRI-84/35 significantly affected Sertoli cell parameters (stimulation in most of the cases) that are important for germ cell development like lactate secretion, LDH activity, aromatase activity (estradiol secretion) and so on. Gossypol in comparison to CDRI-84/35 had a more severe effect on Sertoli cells with complete inhibition of enzyme activities at higher concentrations. CONCLUSION: It is probable that the antispermatogenic action of CDRI-84/35 and gossypol is routed through Sertoli cells by disruption of important cell functions that support spermatogenesis in vivo. However, the two compounds appear to have different course of action in Sertoli cells, ultimately leading to spermatogenic failure.
Subject(s)
Antispermatogenic Agents/pharmacology , Sertoli Cells/drug effects , Sertoli Cells/enzymology , Animals , Aromatase/metabolism , Cells, Cultured , Glucuronidase/metabolism , Gossypol/pharmacology , L-Lactate Dehydrogenase/metabolism , Lactic Acid/metabolism , Male , Piperazines/pharmacology , Rats , Rats, Sprague-Dawley , gamma-Glutamyltransferase/metabolismABSTRACT
Several appropriately substituted 4-(dialkylamino-alkyl)-substituted-styryl-alkyl ketones or acetophenones were prepared and subjected to the Mannich reaction to yield compounds that would incorporate both alpha,beta-unsaturated keto groups and a substituted aminomethyl function with or without another olefinic moiety at position 4. The spermicidal activity of the prepared compounds was evaluated. Several compounds 2d, 4a and 4e were found to possess spermicidal activity at 0.005% concentration, while compounds 2a, 2c, 2f, 3a and 4b were active at 0.01% concentration. Compounds 2a, 2c, 3a, 4a and 4e also inhibited the interaction between recombinant HIV Env and CD4. Out of these, compound 2c was found to be most active.