http://hdl.handle.net/10366/4192 2026-04-24T02:13:05Z http://hdl.handle.net/10366/160788 [EN] Helminth infections are one of the most prevalent parasitic diseases affecting animals and humans worldwide. Anthelmintic resistance to the main drugs used to control these infections in animals, especially ruminants, is a major global problem that needs urgent solutions. The purpose of this study was to design and obtain new benzimidazole (BZ) derivatives to evaluate their in vitro ovicidal and larvicidal activities. Based on previous results from 2-phenylbenzimidazoles and new docking studies of different BZ-containing scaffolds in Teladorsagia circumcincta tubulin four structural groups of BZs were selected. In addition to several new members of those previously reported 2-phenylBZs (type I), some twenty 2-aminoBZ derivatives (type II) and twenty-five BZ amides (types III and IV) were prepared and evaluated for their ability to inhibit egg hatching and larval motility of T. circumcincta with results superior to those previously achieved. Nine of the fifty-five BZs tested displayed ovicidal activity higher than 90%, and fourteen induced more than 30% larval death in the assays at 50 µM. The benzamide BZ 42 showed the best ovicidal EC50 value of 0.92 µM with a selectivity index > 100 respecting HepG2 cells, while the benzylamine BZ 13 attained a higher than 50% larvicidal activity. Notably, the amide BZ 39 displayed both ovicidal (100%) and larvicidal (>50%) activities. The SAR analysis and the docking studies carried out led to the conclusion that, in addition to the effects on tubulin, pending experimental confirmation, there must be other mechanisms by which the evaluated BZs prevent hatching and limit the mobility of the parasitic larvae. 2022-01-01T00:00:00Z http://hdl.handle.net/10366/145219 [EN]Motivation: AutoDock is a very popular software package for docking and virtual screening. However, currently it is hard work to visualize more than one result from the virtual screening at a time. To overcome this limitation we have designed JADOPPT, a tool for automatically preparing and processing multiple ligand-protein docked poses obtained from AutoDock. It allows the simultaneous visual assessment and comparison of multiple poses through clustering methods. Moreover, it permits the representation of reference ligands with known binding modes, binding site residues, highly scoring regions for the ligand, and the calculated binding energy of the best ranked results. Availability and Implementation: JADOPPT, supplementary material (Case Studies 1 and 2) and video tutorials are available at http://visualanalytics.land/cgarcia/JADOPPT.html Contacts: carlosgarcia@usal.es or pelaez@usal.es Supplementary information: Supplementary data are available at Bioinformatics online. 2017-01-01T00:00:00Z http://hdl.handle.net/10366/145069 [EN] We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 𝜇g/mL), but only partial blockade (∼30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ∼70% in both preparations). Preincubation of venom with betulin (200 𝜇g/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. 2015-01-01T00:00:00Z http://hdl.handle.net/10366/141002 [EN] The cobalt crust fungus Terana coerulea (Phanerochaetaceae family) was selected for a bio-guided study after an ethnobotanical survey at the Irati’s Forest (Navarra, Spain) for its local use as antibiotic. Six extracts of increasing polarity, from hexane to hot water, were obtained from powdered dry fungi and tested for cytotoxicity against four human tumour cell lines and one non-tumour primary cell culture. From the most cytotoxic, EtOAc extract, we isolated and identified three terphenyl neolignans: two of them new natural products, named corticins D and E, and one previously described as corticin A, whose earlier structure has been revised. Their structural elucidation and biological evaluation as cytotoxic agents are described. 2017-01-01T00:00:00Z http://hdl.handle.net/10366/22600 Los compuestos químicas presentes en plantas y animales siguen siendo una fuente importante de fármacos y de productos usados en la alimentación, la cosmética y laagricultura entre otros campos, o bien como fuente para la obtención de principios activos de interés biológico y farmacológico. 2008-12-01T00:00:00Z