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A series of 1,3-substituted 8-styrylxanthines (11a-d) was synthesized, under chemo- and regioselective conditions, in a good overall yield. The compounds showed affinity towards both A1 and A2A-adenosine receptors by radioligand binding by means of in vitro assays. The (E)-3-ethyl-1-propyl-8-styrylxanthine (11a) showed the greatest affinity towards the A2A receptor, whereas (E)-3-pentyl-1-propyl-8-styrylxanthine (11d) showed the greatest affinity for the A1 receptor. When the 8-styrylxanthines 11a (A15Et) and 11c (A15Bu) were administrated in rats, which were previously injured with 6-hydroxydopamine at the substantia nigra pars compacta (SNc), the turning behavior decreased 50%. Based on these results we propose to A15Et as a potential compound to treat some symptoms of Parkinson’s disease.

One-third of top-selling drugs are derived from natural products. When only a fraction of the bioactive natural products diversity has been explored, huge opportunities still remain for discovering novel leads for the development of new drugs. Clear cell renal cell carcinoma (ccRCC) is a highly vascular tumour arising from epithelial elements. Mutations in the Von Hippel-Lindau (VHL) gene are responsible for VHL disease and arise in the majority of Renal Cell Carcinoma (RCC) as well as in other types of cancer. Renal carcinoma cell lines with naturally occurring VHL mutations (RCC4 VA) and their genetically matched wild-type VHL (RCC4 VHL) counterparts were seeded onto 96-well plates and allowed to attach overnight. Fungal extracts were tested on both cell lines. Clinically useful antitumor agents were used as positive controls and as reference points to establish the efficacy and selectivity of the new compounds. Renal cell carcinoma cell lines expressing VHL or not were treated with Carboxyfluorescein succinimidyl ester (CFSE). The day after cell inoculation, extracts were added and during the following days of incubation, fluorescence intensity was measured as a surrogate marker for cell viability. The most promising extracts selectively inhibited growth of pVHL-defi- cient cells but not of wild-type VHL cells. We used High Content Bio-imaging, a complete cellular imaging workflow that integrates instruments and software to acquire and analyze images, to evaluate their effect. Cell imaging can reveal effects that would be overlooked by other cell assay approaches. This target-based whole cell screen is a new strategy, which ensures cell permeability and target selectivity especially in natural product screening where natural product purification is a labour of extensive work. This approach permitted a dynamic study where fluorescence was measured without affecting cell viability and enabling a better detection of cytotoxic effects such as autophagy, senescence or late apoptosis.

We present a case report of a chronic graft-versus-host disease manifestation in 33-year-old patient with an unusual complication of vaginal stenosis with complete obstruction after allogeneic bone marrow transplantation for myelocytic leukemia. The patient complained on a progressive dyspareunia and sexual intercourse inability. She has received hormone replacement therapy due to the ovarian failure after the chemotherapy treatment. The hormonal treatment was used in continuous combined manner and hematocolpos wasn’t seen during an abdominal ultrasound examination. The reconstructive surgery was performed by the modified Vecchietti’s neovagina technique with a Remeex® system after histological confirmation of main diagnosis. The immediate postoperative course was uneventful with gradual normalization of sexual function.