EHNA hydrochloride

PDE2 is a novel target for attenuating tumor formation in a mouse model of UVB-induced skin carcinogenesis.[Pubmed:25330380]

PLoS One. 2014 Oct 16;9(10):e109862.

Our previous studies demonstrated that the topical application of caffeine is a potent inhibitor of UVB-induced carcinogenesis and selectively increases apoptosis in tumors but not in non-tumor areas of the epidermis in mice that are at a high risk for developing skin cancer. While this effect is mainly through a p53 independent pathway, the mechanism by which caffeine inhibits skin tumor formation has not been fully elucidated. Since caffeine is a non-specific phosphodiesterase inhibitor, we investigated the effects of several PDE inhibitors on the formation of sunburn cells in mouse skin after an acute exposure to ultraviolet light B (UVB). The topical application of a PDE2 inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA hydrochloride), stimulated epidermal apoptosis compared to control (P<0.01) and to a greater extent than caffeine whereas a PDE4 inhibitor attenuated the epidermal apoptosis compared to control (P<0.01). Since PDE2 hydrolyzes cyclic nucleotides, mainly cGMP, the effects of EHNA hydrochloride on epidermal apoptosis following UVB exposure may be mediated, in part, by increased cGMP signaling. Data demonstrated that the topical application of dibutyryl cGMP stimulated epidermal apoptosis (P<0.01) following an acute exposure to UVB. Treating UVB-pretreated mice topically with 3.1 micromole or 0.8 micromole of EHNA hydrochloride attenuated tumor formation to a greater extent than treating with 6.2 micromole caffeine when these compounds were applied once a day, five days a week for 18 weeks. These observations suggest a novel role for PDE2 in UVB-induced tumorigenesis and that PDE2 inhibitors that mediate cGMP signaling may be useful for the prevention and treatment of skin cancer.

Susceptibility of Trypanosoma evansi to cordycepin.[Pubmed:21620640]

Biomed Pharmacother. 2011 Jun;65(3):220-3.

Drugs, which are effective during the early stage of trypanosomosis, but poorly penetrate the blood-brain barrier, are ineffective when parasites reach the brain and cause encephalitis. In order to seek alternative treatments, the aim of this study was to test the susceptibility of T. evansi to cordycepin in vitro and in rats experimentally infected. In vitro, a significant decrease (P<0.01) in live trypanosomes in the concentrations of 5.0 and 10 mug/mL was observed 1 hour after the beginning of the study, as well as at 3, 6, 9 and 12 hours in all concentrations compared to control. Although no curative effects were observed in the in vivo assay in the majority of groups, the drug was able to maintain parasitemia at low levels, therefore increasing the longevity of rats when compared to positive control group. Rats that received cordycepin alone or in combination with adenosine deaminase inhibitor (ADA: EHNA hydrochloride), did not show trypomastigote forms of the parasite in the bloodstream 24 hours after the administration. These animals remained negative in blood smears on average for 8 days, but thereafter had a recurrence of parasitemia. Among all the infected animals, only three rats in the group treated with the combination of cordycepin (2 mg/kg) and EHNA hydrochloride (2 mg/kg) remained negative during the experimental period. The curative efficacy of 42.5% was confirmed by PCR using T. evansi-specific primers. Thus, we conclude that cordycepin has biological effect against T. evansi, as previously reported in infections by T. brucei, T. cruzi and Leishmania sp. The treatment with cordycepin, when protected by an inhibitor of ADA, can prolong the survival of T. evansi-infected rats and provide curative efficacy.