Sergio Sifontes-Rodríguez- DVM MSc PhD
- Research Associate at National Autonomous University of Mexico
Sergio Sifontes-Rodríguez
- DVM MSc PhD
- Research Associate at National Autonomous University of Mexico
Preclinical and clinical safety and efficacy testing of a parasite-derived peptide with antitumoral activity.
About
82
Publications
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Citations
Introduction
Current institution
Additional affiliations
September 2018 - July 2020
October 2008 - August 2018
Position
- Head of Department
Description
- Research and development of new products with biological activity
January 2000 - September 2007
Position
- Head of Department
Description
- Precinical safety and efficacy testing of vaccines for human use.
Education
January 2012 - December 2016
January 2004 - December 2006
January 2001 - July 2001
Field of study
- Drug Screening against Leishmania, malaria & Trypanosoma
Publications
Publications (82)
Leishmania spp. cause a wide range of human diseases, localized skin lesions, mucocutaneous and visceral infections. In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of Leishmania PP2C that can induce apoptosis in the parasite. The results demonstrated that sanguinarine inhibits, in a dose-...
The use of peptides for cancer immunotherapy is a promising and emerging approach that is being intensively explored worldwide. One such peptide, GK-1, has been shown to delay the growth of triple-negative breast tumors in mice, reduce their metastatic capacity, and reverse the intratumor immunosuppression that characterizes this model. Herein, it...
Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen, whose a...
Citation: Mollineda-Diogo, N.; Sifontes-Rodríguez, S.; Aguirre-García, M.M.; Escalona-Montaño, A.R.; Espinosa-Buitrago, T.; Mondragón-Flores, R.; Mondragón-Castelán, M.E.; Meneses-Marcel, A.; Pérez-Olvera, O.; Sánchez-Almaraz, D.A.; et al. 3-Alkoxy-1-Benzyl-5-Nitroindazole Derivatives Are Potent Antileishmanial Compounds. Int. J. Mol. Sci. 2024, 25...
Drug repositioning is an efficient strategy to search for new treatment alternatives that is especially valuable for neglected parasitic diseases such as leishmaniasis. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERM) that have shown antileishmanial activity. Clomiphene is a SERM structurally similar to tamoxifen whose ant...
Introduction
Leishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases.
Purpose
The obj...
PubChem Bioassays (AID 1063) reported the in vitro testing of 196 441 compounds against Leishmania major promastigotes. Although these results have been publicly available since 2008, limited efforts on further testing of some of these compounds has been published. The aim of the present work was selecting a small set of compounds that were highly...
Background
Currently, there is no safe and effective vaccine against leishmaniasis and existing therapies are inadequate due to high toxicity, cost and decreased efficacy caused by the emergence of resistant parasite strains. Some indazole derivatives have shown in vitro and in vivo activity against Trichomonas vaginalis and Trypanosoma cruzi. On t...
Leishmaniasis is an infectious disease caused by protozoan species in the genera Leishmania and Endotrypanum.
Current antileishmanial drugs are limited due to adverse effects, variable efficacy, the development of resistant
parasites, high cost, parenteral administration and lack of availability in endemic areas. Therefore, active
searching for new...
Leishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases.
Purpose: The objective of th...
Introduction: Amphotericin B is an effective drug for the treatment of the different clinical forms of leishmaniasis. However, there are reports of its ineffectiveness in animals experimentally infected with Leishmania spp. That is why, the objective of the present work was to evaluate the balance of activity-toxicity at amphotericin B doses over 1...
Macrophomina phaseolina and Rhizoctonia solani are considered two major soil-borne pathogens of Phaseolus vulgaris in Cuba. Their management is difficult, not only due to their intrinsic biology as soil-borne pathogens, but also because the lack of active ingredients available against these pathogens. Actinobacteria, a heterogeneous bacterial group...
Introducción:
Los extractos acuosos de las hojas de Jatropha gossypifolia L. son utilizados de forma tradicional en el tratamiento de la leishmaniasis. No existen informes concluyentes sobre su efectividad y su citotoxicidad aunque en estudios recientes ha quedado avalada la utilidad de la planta en el tratamiento de la leishmaniasis utilizando otr...
The development of antimalarial drugs requires performing laboratory experiments that include the analysis of blood smears infected with Plasmodium. Analyzing visually the resulting microscopy images is usually a slow and tedious task prone to errors due to fatigue and subjectivity of the analysts. These facts have motivated the creation of digital...
The development of antimalarial drugs requires performing laboratory experiments that include the analysis of blood smears infected with Plasmodium berghei. Analyzing visually the resulting microscopy images is usually a slow and tedious task prone to errors due to fatigue and subjectivity of the analysts. These facts motivated the creation of digi...
The objective of this work was to determine the best scheme and route for the application of VA-MENGOC-BC .. in mice. 21O Balb / c were immunized with the aforementioned vaccine by the intraperitoneal route (IP-0.5 ml and intramuscular (IM-0.05 mL} with one, two or three inoculations and the corresponding combinations of number of doses and routes...
A-RESUMEN
La leishmaniosis y la enfermedad de Chagas son dos enfermedades olvidadas de alta prevalencia e impacto en la salud pública a escala mundial. Tienen en común que afectan primordialmente a los países más pobres, no existen vacunas eficaces y seguras para prevenirlas, los medicamentos disponibles son caros, tóxicos e ineficaces y cada día e...
The automated identification of markers in medical imaging is one of the issues
proposed in recent years for many tasks with wide application in digital image analysis, but there
is not a universal algorithm for this. We introduce here a low computational cost system based
on the Radon transform to determine markers for watershed segmentation purpo...
RESUMEN El objetivo del presente fue evaluar la actividad in vitro de la furvina frente a microorganismos aislados de la piel de caninos con piodermitis de la ciudad de Santa Clara, Cuba. La resistencia a los agentes antibacterianos se determinó mediante el méto-do de difusión en agar y la actividad in vitro se evaluó cuantitativamente mediante mac...
Despite recent advances in the treatment of some forms of leishmaniasis, the available drugs are still far from ideal due to inefficacy, parasite resistance, toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfuran compounds has been described, as has their activity against Trichomonas vaginalis and other protozoa. Thus, the...
La leishmaniasis constituye una enfermedad parasitaria de elevada prevalencia mundial. La búsqueda racional de nuevos fármacos anti-leishmaniales sigue siendo una prioridad hasta tanto los medios para su prevención y control sean tan limitados. En el presente trabajo se muestran resultados de un esquema de búsqueda racional de nuevos compuestos act...
Aquaculture represents one of the fastestgrowing animal foodproducing sectors worldwide. One of the main challenges is to obtain highvolume production with the highest possible quality, this leads to reduce the use of antibiotics and chemotherapeutics. A promising solution to these problems is the application of immunepotentiatiors mainly in intens...
Aquaculture represents one of the fastest-growing animal food-producing sectors worldwide. One of the main challenges is to obtain high-volume production with the highest possible quality, this leads to reduce the use of antibiotics and chemotherapeutics. A promising solution to these problems is the application of immune- potentiatiors mainly in i...
The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccin...
The AFCo1 cochleate is a potential novel adjuvant derived from Neisseria meningitidis B proteoliposome. The aim of this study was to assess the safety of AFCo1 by repeated doses in Sprague Dawley rats. Rats were grouped for treatment with AFCo1, placebo formulation or control. Four similar doses of the test substance were instilled every five days....
Cochleates are supramolecular structures that have been developed either as vaccine adjuvants or as drug carriers. The main difference relays on the kind of phospholipids used to form the cochleate and the active compound that is entrapped. Cochleates used as drug carriers generally consists of phosphatidylserine entrapping an active drug molecule;...
The AFCo1 cochleate is a potential novel adjuvant derived from Neisseria meningitidis B proteoliposome.
The aim was to assessing the safety of AFCo1 by single and repeated doses in Sprague Dawley rats.
Rats were grouped for treatment with AFCo1, placebo formulation or control. The first study was a single intranasal dose of 100 μl and monitoring bo...
In this work a simple and novel method to evaluate the efficacy of compounds on intracellular Leishmania amastigotes by using a fluorometric assay has been developed. The new method is sensitive, easy to perform and scalable for high throughput and therefore it could be validated for screening of new anti-leishmanial agents.
La leishmaniasis cutánea constituye la forma clínica de mayor prevalencia mundial de esta enfermedad. El desarrollo de modelos animales más relevantes constituye una prioridad en la búsqueda de nuevos anti-leishmaniales, pues por ejemplo, la anfotericina B que es el fármaco clínicamente más eficaz resulta poco activo en ratones infectados experimen...
Malaria is one of the most severe infectious diseases, no new antimalarial has been introduced since 1996 and even the last clinically efficacious class, the artemisinins, is currently compromised by parasite resistance. Thus, continuous search for new therapeutic alternatives is needed. In the present work, a molecular similarity search for compou...
The aim of this work was to evaluate the microencapsulation by spray-drying of inactivated Vibrio cholerae, using methacrylic copolymers Eudragit® L30D-55 and FS30D. The microparticles obtained presented a particle size around 3.0 μm. The preparation temperature affected the morphology and the antigenicity of microparticles, but it did not affect t...
Here we further investigate the pharmacological and toxicological properties of a cholera vaccine based on inactivated whole cells presented in either enteric coated (COA) or uncoated (U/C) tablet formulation from Vibrio cholerae C7258 strain. Tablets were dispersed in 2mL drinking water and administered orally to Sprague Dawley rats distributed in...
A live attenuated vaccine candidate against human cholera has been developed from the genetically modified Vibrio cholerae O1, biotype El Tor, serotype Ogawa, 638 strain. Previous single dose toxicity and local tolerance studies have demonstrated that the product is innocuous in Sprague Dawley rats by oral route and single dose. The present paper d...
Los estudios de tolerancia local para productos vacunales resultan fundamentales como requisitos regulatorios para los estudios preclínicos. En este ensayo se utilizaron 48 ratas Sprague Dawley, de ambos sexos, con un peso corporal de 180-220 g, suministradas por el Centro Nacional para la Producción de Animales de Laboratorio, yuna duración de 17...
Mycobacterium tuberculosis is a facultative intracellular pathogen for which cell-mediated immunity is considered the major component of the immune response. For many decades, the prevailing scientific view has been the antibodies have little or no role in modifying the course of M. tuberculosis infection. In recent years, several studies have chal...
The preclinic studies achieve the approval of the clinical assays. Some vaccines conceive a toxicity assay for unique dose, for repeated dose and local tolerance, as well as studies of reproduction toxicology. These studies constitute a fundamental link in the chain of regulatory requirements of the preclinic toxicologic studies since they allow to...
La vacuna vax-TET® está indicada en la prevención del tétanos y es efectiva si se logra un completo y apropiadoesquema de inmunización. Para investigar el potencial tóxico de este producto se realizó una prueba toxicológica conuna dosis única, por vía intramuscular, en un volumen de 0,2 mL en ratas Sprague Dawley. La composición de lavacuna de ensa...
The present work had the aim of testing the efficacy and safety of VA-MENGOC-BC®, the antimeningococcal vaccine against serogroups B and C. Male and female, young-adult, Balb/cj mice and Sprague Dawley rats (CENPALAB, Havana) were used. The meningococcal diseased was reproduced in mice treated with virulence enhancement agents like mucin, iron dext...
The lack of naturally susceptible laboratory animal species to Neisseria meningitidis infection has historically hampered the non-clinical pharmacological testing of candidate vaccines and therapeutic means. Several animal models have been developed; however, none of them has been capable of replicating the human disease integrally. Mammalian hosts...
Pseudomonas aeruginosa constituye uno de los agentes patógenos oportunistas de mayor frecuencia de aislamiento en los diversos procesos infecciosos, por lo que es reconocido como un gran problema de salud a nivel mundial. Al no existir un fármaco de alta efectividad ni vacunas disponibles contra esta bacteria, se emplea una terapia con inmunoglobul...
Salmonella enterica serovar Typhi es un microorganismo que provoca más de 16 millones de casos de fiebre tifoidea conaproximadamente 600 000 muertes al año en todo el mundo. Dentro de las vacunas antitifoídicas la de polisacárido capsular Vi haencontrado, gracias a sus incuestionables ventajas, una gran aceptación entre productores y consumidores....
Tuberculosis is a serious infectious disease in many developing countries. The lack of an effective vaccine for preventing this disease has stimulated the search for new vaccine candidates against Mycobacterium tuberculosis. In the present work, the construction of a genomic expression library of M. tuberculosis in a eukaryotic expression vector wa...
The preclinical testing of vaccines and adjuvants has significantly evolved during the last decade. Concerns regarding the use of prophylactic vaccines are essentially different to those for small molecules. As a result, new approaches for the experimental design of preventive vaccines preclinical studies have arisen. The main objectives are demons...
Preclinical toxicity testing is a key factor among regulatory requisites to license a vaccine and one adjuvant. Alternative routes to parenteral immunization, as the nasal one, are a present day trend, due mainly to their implied advantages. Cochleate derived from proteoliposome of Neisseria meningitidis B is a promising mucosal adjuvant an a poten...
En el presente ensayo se evaluó la toxicidad por dosis única de la vacuna antitetánicaantidiftérica (VA-DIFTET®) en ratas Sprague-Dawley. Para ello se utilizó la vía intramuscular porser la propuesta a usar en humanos. Se administraron 0,3 mL de la vacuna o sus componentes a un total de 20 animales por grupo (10 de cada sexo). Los mismos se observa...
(EN)The invention relates to the action of representatives of a novel family of products in relation to different strains of Leishmania and Trypanosoma cruzi for the treatment of cutaneous, mucocutaneous and visceral leishmaniasis as well as trypanosomiasis. The aforementioned products have demonstrated greater effectiveness than medicaments alread...
Vaccines obtained through DNA could be a very promising tool in tuberculosis (TB) control. However, they do not afford, at the moment, an adequate protection in experimental models, which does happen when using BCG. In the current study, a histopathological evaluation was performed in mice inoculated with a genomic expression library of M. tubercul...
La vacuna antitifoídica vax-TyVi® consiste en una preparación de polisacárido capsular Vi de Salmonella typhi, el cual es diluido en una solución buffer isotónica solución amortiguador, a la que se le añade fenol como preservo. Cada dosis de 0,5 mL contiene 25 μg de polisacárido como sustancia activa. En nuestro país el esquema de vacunación contra...
The single-dose toxicological test for the leptospirosis vaccine vax-SPIRAL was made in rats. No clinical toxicity symptoms were found. The differences between the evaluated variables were not important from the biological point of view.
The single-dose toxicological test for the leptospirosis vaccine vax-SPIRAL was made in rats. No clinical toxicity symptoms were found. The differences between the evaluated variables were not important from the biological point of view.
Generalmente, Pseudomona. aeruginosa es considerada un patógeno oportunista. Bajo ciertas condiciones esta bacteria puede infectar diferentes tipos de heridas, particularmente quemaduras, pero también el tracto urinario y respiratorio. Esta bacteria se asocia con neumonía, endocarditis, meningitis y algunas cepas producen grandes cantidades de poli...
Las pruebas preclínicas de toxicidad en dosis única y en dosis repetidas brindan una valiosa información sobre la seguridad del producto, al incluir el estudio macroscópico e histopatológico de órganos importantes, así como evaluaciones de las vías de administración y el régimen de dosificación. Cuba desarrolló una vacuna polivalente de células ina...
Hasta la fecha se han desarrollado varios modelos experimentales para la reproducción experimental de la enfermedad meningocócica humana, cuya utilidad en la evaluación de la eficacia de medios de inmunización y terapia, así como en el estudio de la patogenia de laenfermedad es incuestionable. En el presente trabajo se describe la evaluación de la...
It was demonstrated that there is a relation of cell concentration with the parasite reading in an ELISA reader. It was determined that absorbance showed significant values in wavelengths of visible range and the possible minimum wavelength (450 nm)was chosen to guarantee the maximum sensitivity. Likewise, it was confirmed that absorbance significa...
It was demonstrated that there is a relation of cell concentration with the parasite reading in an ELISA reader. It was determined that absorbance showed significant values in wavelengths of visible range and the possible minimum wavelength (450 nm)was chosen to guarantee the maximum sensitivity. Likewise, it was confirmed that absorbance significa...
La alta incidencia mundial de meningitis meningocócica por Neisseria meningitidis serogrupo B (N. meningitidis) movilizó los recursos de la ciencia hacia su enfrentamiento en un período corto de tiempo. Para el estudio de esta enfermedad fue imprescindible desarrollar modelos experimentales que posibilitaran caracterizar no sólo la capacidad inmuno...
Toxicological tests on vaccines are increasingly exigent, and specific and non-specific safety tests are not considered sufficient any longer. Vax-SPIRAL is an inactivated whole-cell leptospiral vaccine adsorbed to aluminum hydroxide. The toxicity test by single dose in at least one animal species is included among the preclinical tests demanded to...
La fiebre tifoidea constituye una enfermedad propia del hombre. La misma es causada por Salmonella typhi y produce una respuesta inflamatoria en el tracto intestinal. Con el fin de establecer su control por vacunación el Instituto Finlay ha desarrollado una vacuna a partir del polisacárido capsular Vi. Para su estudio experimental no existe un mode...
RESUMEN Las dificultades que aún persisten en el tratamiento de las leishmaniosis justifican el ensayo de la acción de nuevos productos sobre formas del parásito, en la búsqueda de una alternativa terapéutica a esta parasitosis. Dada la necesidad de establecer un procedimiento para evaluar la actividad in vitro de productos naturales y sintéticos e...
Una vez estudiada la toxicidad de la vacuna VA-DIFTET® (vacuna antidiftérica antitetánica) por administración a dosis única en dos especies de animales, se impone la evaluación a dosis repetida, teniendo en cuenta que el esquema de inmunización en humanos prevé la aplicación de tres dosis cuando el componente pertusis de la DPT está contraindicado....
To know the activity of antimeningococcal immunoglobulin, Balb/c mice of 18-22 g of body weight were challenged with 5 serotype B strains of Neisseria meningitidis (Nm) isolated from patients of different Latin American countries. The specific antimeningococcal Ig was extracted from the serum of volunteers previously vaccinated with the antimeningo...
VA-MENGOC-BC is a vaccine against B and C serogroups of Neisseria meningitidis. Its effectiveness at population level has been shown after the application of the vaccine in Cuba, Brazil, Argentina and Colombia. In vitro assays are not always able to reproduce the microorganism-host relationships and this makes it necessary to compile and standardiz...
The epidemiological situation of bacterial meningitis is increasing dramatically. There is no doubt that the lack of proper animal models has hampered the achievement of effective prophylactic and therapeutic means. We report the characterization of the experimental disease caused by Haemophilus influenzae type b (Hib) in mice, taking into account...
Experimental leptospirosis was reproduced in golden Syrian hamsters (Mesocricetus aureatus). Evaluation of three Leptospira serogroups (canicola, icterohaemorrhagiae and pomona) was carried out regarding their virulence, production of symptoms and lethal activity. Macroscopic and microscopic studies of tissue lesions were also made. Animals were in...
Infants rats, a well known model for the experimental reproduction of bacterial meningitis, were used by us to test the protective potential of antibodies developed in humans who had been vaccinated with the Cuban antimeningitis vaccine (VA-MENGOCBC). Newborn rats were inoculated by the intraperitoneal and intranasal routes with suspensions of Neis...
Toxicological Evaluation in Mice of an Initial Safe Single Dose for Vax-SPIRAL, a Cuban Vaccine against Leptospirosis. Toxicological tests on vaccines are increasingly exigent, and specific and non-specific safety tests are not considered sufficient any longer. Vax-SPIRAL is an inactivated whole-cell leptospiral vaccine adsorbed to aluminum hydroxi...
Questions
Question (1)
Hi. According to many references N-methy-pyrrolidone (NMP) is used for the formulation of drugs intended for the subcutaneous injection of drugs in humans and animals. The concentration used for subcutaneous implants is about 50 %, but we have found severe local irritation when injecting 10-18 % NMP (Pharmasolve) by the subcutaneous route in mice. Have any of you had such experience? Any hint to solve the problem? Thanks in advance.
Sergio
