Angiodysplasia is a frequent cause of persistent gastrointestinal (GI) hemorrhage in elderly patients. Although GI bleeding isn’t the most common manifestation in patients with bleeding disorders, when present, it represents a challenging complication. We describe a 62-year-old patient with Glanzmann’s thrombasthenia, who used thalidomide for severe and recurrent GI bleeding. For 6 months, the patient experienced temporary control of GI bleeding with thalidomide in a daily oral dose of 100 mg. The anti-angiogenic effects of thalidomide have recently been explored by several groups, particularly in the management of bleeding from angiodysplasia, including cases with von Willebrand disease. Here, we review the relevant descriptions of the use of thalidomide in this situation, and also discuss potential reasons why we observed only a temporary control of the GI bleeding in our patient, such as the use of low-dose regimen due to limitations posed by thalidomide side effects.

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Herein we describe the antiproliferative effects of two natural dibenzo[b,f]oxepines, pacharin (PAC) and bauhiniastatin-1 (BAU), isolated from Bauhinia acuruana on breast cancer cell line and the mode of action underlying the cytotoxicity. Both compounds were cytotoxic in a panel of six tumor lines analyzed by MTT assay and IC50 values ranged from 7.8 to 45.1 μM, including upon human breast adenocarcinoma (MCF-7) cells. In contrast, none of the compounds was cytotoxic on normal human peripheral blood mononuclear cells (IC50>100 μM). Then, MCF-7 cells treated with PAC and BAU 20 µM during 24h presented a reduction in cell volume and intensification of chromatin condensation, DNA fragmentation and apoptotic cells, whose findings became more evident after 48h of exposure. Anti-apoptotic B-cell lymphoma-2 (BCL-2) family members, such as Myeloid cell leukemia-1 (MCL-1) and B-cell lymphoma-extra large (Bcl-xL) are important targets in cancer cell, since their overexpression confer resistance to cancer treatments. A significant reduction of the MCL-1 protein levels in MCF-7 cells after 24h of treatment with PAC and BAU at 20 μM was observed, while the Bcl-xL protein content was reduced in BAU-treated cells at 40 μM only. The cytotoxic effects of PAC and BAU are likely linked to the MCL-1 inhibition, which leads to the apoptosis of breast adenocarcinoma cells.

The development of chemotherapy agents without side effects is a major challenge, since traditional medicines usually have undesirable properties such as high toxicity, resistance and low bioavailability. In this sense, computational methods play a crucial role in the discovery and optimization of new drugs, as they combine speed and efficiency with low cost. The 1,2,4-oxadiazoles are one of the main classes of heterocyclics due to their numerous biological applications. In this work, we report the synthesis, antineoplastic evaluation and in silico study of a new 1,2,4-oxadiazole. The (S)-N-(1-hydroxy-3-methylbutan-2-yl)-3-(p-toluyl)-1,2,4-oxadiazole-5-carboxamide was obtained after two reaction steps in excellent yield. Although it has shown low activity in relation to the MCF-7, HCT116 and HL60 tumor cell lines, the molecular docking study indicates that this compound acts in the colchicine site and can inhibit tubulin polymerization. From the calculation of pharmacokinetic properties by the SwissADME and Osiris Property Explorer programs, it is possible to infer that the compound meets the Lipinski rules presenting good oral bioavailability and low toxicity.