TY - JOUR
T1 - Exploratory toxicology studies of 2,3-substituted imidazo[1,2-a]pyridines with antiparasitic and anti-inflammatory properties
AU - Serrano-Contreras, Jose Iván
AU - Melendez-Camargo, María Estela
AU - Márquez-Flores, Yazmín Karina
AU - Soria-Serrano, Martha Patricia
AU - Campos-Aldrete, María Elena
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background: Trichomoniasis and amoebiasis are neglected diseases and still remain as a global health burden not only for developing countries, from where are endemic, but also for the developed world. Previously, we tested the antiparasitic activity of a number of imidazo[1,2-a]pyridine derivatives (IMPYs) on metronidazole-resistant strains of Entamoeba Hystolitica (HM1:IMSS), and Trichomonas Vaginalis (GT3). Their anti-inflammatory activity was also evaluated. Objective: The present work is a part of a project whose aim is to find new alternatives to standard treatments for these maladies, and to address the current concern of emerging resistant parasite strains. Here we report a non-clinical study focused on exploratory toxicology assays of seven IMPYs that showed the best antiparasitic and/or anti-inflammatory properties. Methods: Acute, and subacute toxicity tests were carried out. After 14-day oral treatment, liver and kidney functionality assays in combination with chemometric methods were implemented to detect hepatic and/or kidney damage. Results: Some compounds produced off-target effects. Vehicle effects were also detected. However, no signs of hepatic or renal toxicity were observed for any IMPY. Conclusion: These compounds can continue non-clinical evaluations, and if possible, clinical trials as new candidates to treat trichomoniasis and amoebiasis, and inflammatory diseases. Further studies are also needed to fully elucidate a proposed dual effect that may exert these molecules against trichomoniasis and amoebiasis, which may also signify a novel mechanism of action to treat these infections.
AB - Background: Trichomoniasis and amoebiasis are neglected diseases and still remain as a global health burden not only for developing countries, from where are endemic, but also for the developed world. Previously, we tested the antiparasitic activity of a number of imidazo[1,2-a]pyridine derivatives (IMPYs) on metronidazole-resistant strains of Entamoeba Hystolitica (HM1:IMSS), and Trichomonas Vaginalis (GT3). Their anti-inflammatory activity was also evaluated. Objective: The present work is a part of a project whose aim is to find new alternatives to standard treatments for these maladies, and to address the current concern of emerging resistant parasite strains. Here we report a non-clinical study focused on exploratory toxicology assays of seven IMPYs that showed the best antiparasitic and/or anti-inflammatory properties. Methods: Acute, and subacute toxicity tests were carried out. After 14-day oral treatment, liver and kidney functionality assays in combination with chemometric methods were implemented to detect hepatic and/or kidney damage. Results: Some compounds produced off-target effects. Vehicle effects were also detected. However, no signs of hepatic or renal toxicity were observed for any IMPY. Conclusion: These compounds can continue non-clinical evaluations, and if possible, clinical trials as new candidates to treat trichomoniasis and amoebiasis, and inflammatory diseases. Further studies are also needed to fully elucidate a proposed dual effect that may exert these molecules against trichomoniasis and amoebiasis, which may also signify a novel mechanism of action to treat these infections.
KW - imidazo[1,2-a]pyridines
KW - multivariate analysis
KW - off-target effect
KW - partial least squares
KW - vehicle effect
UR - http://www.scopus.com/inward/record.url?scp=85159578990&partnerID=8YFLogxK
U2 - 10.1093/toxres/tfac046
DO - 10.1093/toxres/tfac046
M3 - Artículo
C2 - 36337253
AN - SCOPUS:85159578990
SN - 2045-452X
VL - 11
SP - 730
EP - 742
JO - Toxicology Research
JF - Toxicology Research
IS - 5
ER -