31 research outputs found

    Trichomonas vaginalis: la versatilidad de un parásito tenaz

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    Trichomonosis is one of the most prevalent nonviral sexually transmitted infection (S.T.I.) worldwide, with an estimated 276 million cases per year according to WHO overview. Little attention is paid to this disease, although more than 50% of S.T.I. curable are caused by this protozoon. Clinically, Trichomonas vaginalis infection can produce a wide range of pathological manifestations, from asymptomatic presentation to severe inflammatory and invasive lesions in the genitourinary tract of both men and women. The possible role displayed by T. vaginalis as a viral vector might also explain its role as a risk factor in the development of cervical and prostate neoplasia. In addition, trichomonosis is strongly associated with transmission and acquisition of other bacterial and viral pathogens like HIV. T. vaginalis is a very complex organism and has developed diverse mechanisms for the colonization of the genitourinary tract probably due to its extensive genome. This parasite must survive in a hostile environment exposed to continue fluctuations. Surprisingly, T. vaginalis possesses one of the largest and most repetitive genomes, with a core set of 60,000 protein-coding genes. According to all these features, T. vaginalis could be considered an excellent model of parasite to be studied in order to better understand the dynamics and immune evasion mechanisms of such versatile parasite.La tricomonosis urogenital humana, causada por el parásito Trichomonas vaginalis, es una de las infecciones de transmisión sexual (I.T.S.) de mayor prevalencia en el mundo, con un total de 276 millones de casos cada año, según la OMS.Algunos autores la han calificado como una enfermedad desatendida u olvidada ligada a la pobreza, a pesar de que más del 50% de las I.T.S. curables se deben a este agente etiológico. La tricomonosis cursa con un rango amplio de manifestaciones clínicas, que van desde casos asintomáticos hasta cuadros más graves e invasivos de los conductos genitourinarios. Se ha relacionado la infección con el riesgo de adquisición y transmisión del VIH y de lesiones preneoplásicas de cérvix y próstata. Este protozoo parásito presenta una gran variabilidad intraespecífica en su comportamiento patogénico, probablemente por el tamaño y complejidad de su genoma, con más de 60.000 genes codificantes. Es capaz de sobrevivir y colonizar un nicho complejo sometido a constantes fluctuaciones, el aparato genitourinario, pasando desapercibido en muchos casos. El tamaño y complejidad de su genoma convierten a T. vaginalis en un parásito de gran interés científico para el estudio de los mecanismos de patogenia y evasión de la respuesta inmune

    Antiparasitic properties of cantharidin and the blister beetle berberomeloe majalis (Coleoptera: Meloidae)

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    Cantharidin (CTD) is a toxic monoterpene produced by blister beetles (Fam. Meloidae) as a chemical defense against predators. Although CTD is highly poisonous to many predator species, some have evolved the ability to feed on poisonous Meloidae, or otherwise beneficially use blister beetles. Great Bustards, Otis tarda, eat CTD-containing Berberomeloe majalis blister beetles, and it has been hypothesized that beetle consumption by these birds reduces parasite load (a case of self- medication). We examined this hypothesis by testing diverse organisms against CTD and extracts of B. majalis hemolymph and bodies. Our results show that all three preparations (CTD and extracts of B. majalis) were toxic to a protozoan (Trichomonas vaginalis), a nematode (Meloidogyne javanica), two insects (Myzus persicae and Rhopalosiphum padi) and a tick (Hyalomma lusitanicum). This not only supports the anti-parasitic hypothesis for beetle consumption, but suggests potential new roles for CTD, under certain conditions.This research was funded by MINECO/FEDER, Spain, Grant no. CTQ2015-64049-C3-1-R; Ministerio de Economía y Competitividad, Spain (MINECO/FEDER), Grant no. CGL2017-87206-

    Promising hit compounds against resistant trichomoniasis: Synthesis and antiparasitic activity of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles

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    A series of 11 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles (2–12) has been prepared starting from 1-benzyl-5-nitroindazol-3-ol 13, and evaluated against sensitive and resistant isolates of the sexually transmitted protozoan Trichomonas vaginalis. Compounds 2, 3, 6, 9, 10 and 11 showed trichomonacidal profiles with IC50 < 20 µM against the metronidazole-sensitive isolate. Moreover, all these compounds submitted to cytotoxicity assays against mammalian cells exhibited low non-specific cytotoxic effects, except compounds 3 and 9 which displayed moderate cytotoxicity (CC50 = 74.7 and 59.1 µM, respectively). Those compounds with trichomonacidal effect were also evaluated against a metronidazole-resistant culture. Special mention deserve compounds 6 and 10, which displayed better IC50 values (1.3 and 0.5 µM respectively) than that of the reference drug (IC50 MTZ = 3.0 µM). The high activity of these compounds against the resistant isolate reinforces the absence of cross-resistance with the reference drug. The remarkable trichomonacidal results against resistant T. vaginalis isolates suggest the interest of 3-(ω-aminoalkoxy)-1-benzyl-5-nitroindazoles to be considered as good prototypes to continue in the development of new drugs with enhanced trichomonacidal activity, aiming to increase the non-existent drugs to face clinical resistance efficiently for those patients in whom therapy with 5-nitroimidazoles is contraindicated

    Thio- and selenosemicarbazones as antiprotozoal agents against Trypanosoma cruzi and Trichomonas vaginalis

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    Herein, we report the preparation of a panel of Schiff bases analogues as antiprotozoal agents by modification of the stereoelectronic effects of the substituents on N-1 and N-4 and the nature of the chalcogen atom (S, Se). These compounds were evaluated towards Trypanosoma cruzi and Trichomonas vaginalis. Thiosemicarbazide 31 showed the best trypanocidal profile (epimastigotes), similar to benznidazole (BZ): IC50 (31)=28.72 μM (CL-B5 strain) and 33.65 μM (Y strain), IC50 (BZ)=25.31 μM (CL-B5) and 22.73 μM (Y); it lacked toxicity over mammalian cells (CC50 > 256 µM). Thiosemicarbazones 49, 51 and 63 showed remarkable trichomonacidal effects (IC50 =16.39, 14.84 and 14.89 µM) and no unspecific cytotoxicity towards Vero cells (CC50 ≥ 275 µM). Selenoisosters 74 and 75 presented a slightly enhanced activity (IC50=11.10 and 11.02 µM, respectively). Hydrogenosome membrane potential and structural changes were analysed to get more insight into the trichomonacidal mechanism.Junta de Andalucía Grant PID2020- 116460RB-I00, funded by MCIN/AEI/10.13039/50110001103

    "Trichomonas vaginalis": corroboración experimental de modelos virtuales de cribado farmacológico y caracterización biomolecular de aislados

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    Tesis inédita de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Parasitología, leída el 16-12-2015Depto. de Microbiología y ParasitologíaFac. de FarmaciaTRUEunpu
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