Cytotoxic effect of novel dehydroepiandrosterone derivatives on different cancer cell lines.

The aim of this study was to determine the cytotoxic effect of human cancer cells on three series of novel dehydroepiandrosterone derivatives containing triazole or pyrazole rings at C-17 and an ester moiety at C-3 of the androstane skeleton. The panel cancer cells used in this study were the following: PC-3, MCF-7 and SKLU-1. The results from this study indicated that the steroidal derivatives 4a-4e and 4f-4k showed the highest cytotoxic potency. This difference in this activity could be attributed to the ability of the triazole (three nitrogen atoms) to form stronger hydrogen bonds with the active site of the cell as compared to the pyrazole group having two nitrogen atoms. Compounds 4f-4k having an aromatic ester at C-3 showed an enhanced cytotoxic activity as compared to their aliphatic counterparts 4a-4e. Apparently the electronegative phenyl ring increased the polarity of the molecule, thus increasing the dipole-dipole association of the steroidal molecule with the reactive site of the cell.

Detrimental effects of hyperandrogenism on uterine functions.

The aim of the present work was to study some of the adverse effects produced by hyperandrogenism on the uterine function. Daily injection of dehydroepiandrosterone (DHEA: 6 mg/ 100 g body weight, sc) for 20 consecutive days induced polycystic ovaries in BALB/c mice. In this model, we found that DHEA produced alterations on uterine histology closely related to the development of tumour structures. In addition, hyperandrogenism induced a pro-inflammatory and a pro-oxidant condition represented by increased levels of prostaglandin F2 alpha production and uterine nitric oxide synthase (NOS) activity and by a decrease in both superoxide dismutase (SOD) and catalase (CAT) activities together with a decrease in the levels of the antioxidant metabolite glutathione (GSH). DHEA also induced an increase in CD4+ together with a decrease in the CD8+ T lymphocytes that infiltrate the uterine tissue. We conclude that this intricate network of regulators could be responsible for the low rate of implantation observed in women with polycystic ovary syndrome.

Dehydroepiandrosterone, epiandrosterone and synthetic derivatives inhibit Junin virus replication in vitro.

In the present paper the in vitro antiviral activity of dehydroepiandrosterone (DHEA), epiandrosterone (EA) and 16 synthetic derivatives against Junin virus (JUNV) replication in Vero cells was studied. DHEA and EA caused a selective inhibition of the replication of JUNV and other members of the Arenaviridae family such as Pichinde virus and Tacaribe virus. The compounds were not virucidal to cell-free JUNV. The impairment of viral replication was not due to an inhibitory effect of the steroids on virus adsorption or internalization. An inhibitory effect of the compounds on JUNV protein synthesis and both intracellular and extracellular virus production was demonstrated. A partial inhibitory action on cell surface expression of JUNV glycoprotein G1 was also detected on DHEA- and EA-treated cultures. Like DHEA and EA, three compounds obtained from EA by chemical synthesis showed selectivity indexes higher than ribavirin, the only antiviral compound that has shown partial efficacy against arenavirus infections.