Search results for " Farm"

Design, synthesis and biological evaluation of new anticancer drugs: FGFR inhibitors

2021

Fibroblast growth factor receptors (FGFRs) constitute a family of tyrosine kinases receptors (RTKs) that exert pivotal physiological functions in human embryonic and adult tissues. Hyperactivated FGFR signaling drives tumorigenesis in multiple cancer types, including lung and brain cancers. Great effort has been laid on the development of new compounds that specifically target the FGFR axis. However, cancer cell- based and microenvironmental resistance mechanisms against FGFR inhibitors often arise and are currently poorly understood. Furthermore, FGFR-targeted therapy often presents different side effects, e due to the broad biological spectrum of the FGFR signaling axis as well as to its …

Synthesis, Anti-Inflammatory Activity, and in Vitro Antitumor Effect of a Novel Class of Cyclooxygenase Inhibitors: 4-(Aryloyl)phenyl Methyl Sulfones

2010

Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole derivative 33 was further tested in vivo for its ant…

Nutrient removal by rice–wheat cropping system as influenced by crop establishment techniques and fertilization options in conjunction with microbial…

2020

AbstractNutrient uptake by the rice–wheat cropping system (RWCS) is an important indicator of soil fertility and plant nutrient status. The hypothesis of this investigation was that the rate and sources of nutrient application can differentially influence nutrient removal and soil nutrient status in different crop establishment techniques (CETs). Cropping system yield was on par in all the CETs evaluated, however, there were significant changes in soil nutrient availability and microbiological aspects. The system nitrogen (N), phosphorus (P), potassium (K) and zinc (Zn) uptake in aerobic rice system followed by zero tillage wheat (ARS-ZTW) was 15.7–17.6 kg ha−1, 0.7–0.9 kg ha−1, 7–9.8 kg ha…

1,2,4-Amino-triazine derivatives as pyruvate dehydrogenase kinase inhibitors: Synthesis and pharmacological evaluation

2023

: Among the different hallmarks of cancer, deregulation of cellular metabolism turned out to be an essential mechanism in promoting cancer resistance and progression. The pyruvate dehydrogenase kinases (PDKs) are well known as key regulators in cells metabolic process and their activity was found to be overexpressed in different metabolic alerted types of cancer, including the high aggressive pancreatic ductal adenocarcinoma (PDAC). To date few PDK inhibitors have been reported, and the different molecules developed are characterized by structural chemical diversity. In an attempt to find novel classes of potential PDK inhibitors, the molecular hybridization approach, which combine two or m…

Bioactive pyrrole-based compounds with target selectivity

2020

The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of compounds for pharmaceutical application, most of which are based on N-heterocyclic motifs. Among these, the pyrrole ring is one of the most explored heterocycles in drug discovery programs for several therapeutic areas, confirmed by the high number of pyrrole-based drugs reaching the market. In the present review, we focused on pyrrole and its hetero-fused derivatives with anticancer, antimicrobial, and antiviral activities, reported in the literature between 2015 and 2019, for which a specific target was identified, being resp…

Glutamate and opioid antagonists modulate dopamine levels evoked by innately attractive male chemosignals in the nucleus accumbens of female rats

2017

Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist b-funaltrexamine into the posterior ventral tegmental area does no…

Anti-Inflammatory Activity of Citrus bergamia Derivatives: Where Do We Stand?

2016

Inflammatory diseases affect a large portion of the worldwide population, and chronic inflammation is a major risk factor for several dangerous pathologies. To limit the side effects of both synthetic and biological anti-inflammatory drugs, the use of herbal medicines, nutraceuticals and food supplements has increased tremendously as alternative and/or complementary medicine to treat several pathologies, including inflammation. During the last decades, the biological properties of Citrus bergamia (bergamot) derivatives have obtained important scientific achievements, and it has been suggested their use in a context of a multitarget pharmacological strategy. Here, we present an overview of t…

REM sleep behavior disorder in a patient with frontotemporal dementia

2010

We describe a patient with frontotemporal dementia (FTD), a tauopathy, who also showed clinical and polysomnographic features of REM sleep behavior disorder (RBD). The patient is a 78-year-old male with a 1 year history of behavioral dysfunction involving emotion, character and social functioning. Brain imaging and the results of neuropsychological testing were consistent with a diagnosis of FTD. Sleep symptom onset occurred some years before the behavioral changes, and consisted of unpleasant dreams, vocalization, and prominent motor behaviors. A polysomnography confirmed the diagnosis of RBD. Our findings support the hypothesis that RBD, although more frequent in synucleinopathies, might …

An intraoral drug delivery device for long term therapies: application in Alzheimer’s disease

2009

Application of molecular topology to the prediction of antiparasitic activity against Giardia intestinalis and Trichomonas vaginalis of 2-Acylamino-n…

2020

Giardia intestinalis y Trichomonas vaginalis destacan por su importancia clínica. G. intestinalis causa la giardiosis, una parasitosis de gran importancia epidemiológica y clínica por presentar una elevada prevalencia. T. vaginalis causa la tricomoniasis, la enfermedad de transmisión sexual (ETS) no viral con mayor incidencia del mundo. Ambas parasitosis comparten el mismo tratamiento farmacológico: los nitroimidazoles. Se ha aplicado la topología molecular en la búsqueda de derivados del 2-Acylamino-nitro-1,3-tiazol con actividad antiparasitaria frente a G. intestinalis y T. vaginalis . Con el análisis lineal discriminante se obtuvo un modelo capaz de clasificar correctamente el 92,85 % de…