Search results for "PHARMACOLOGY"

A Review of the Mycotoxin Enniatin B

2017

Mycotoxin enniatin B (ENN B) is a secondary metabolism product by Fusarium fungi. It is a well-known antibacterial, antihelmintic, antifungal, herbicidal, and insecticidal compound. It has been found as a contaminant in several food commodities, particularly in cereal grains, co-occurring also with other mycotoxins. The primary mechanism of action of ENN B is mainly due to its ionophoric characteristics, but the exact mechanism is still unclear. In the last two decades, it has been a topic of great interest since its potent mammalian cytotoxic activity was demonstrated in several mammalian cell lines. Moreover, the co-exposure in vitro with other mycotoxins enhances its toxic potential thro…

Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: Focus on heteroreceptor complexes and related…

2019

Neuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe heteroreceptor complexes between GPCR and RTKs in the central nervous system (CNS) and their …

Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluat…

2017

Abstract Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562 cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562 cells than 13b and 14b. Analyses perfo…

Increased Motor-Impairing Effects of the Neuroactive Steroid Pregnanolone in Mice with Targeted Inactivation of the GABAA Receptor γ2 Subunit in the …

2016

Endogenous neurosteroids and neuroactive steroids have potent and widespread actions on the brain via inhibitory GABAA receptors. In recombinant receptors and genetic mouse models their actions depend on the α, β, and δ subunits of the receptor, especially on those that form extrasynaptic GABAA receptors responsible for non-synaptic (tonic) inhibition, but they also act on synaptically enriched γ2 subunit-containing receptors and even on αβ binary receptors. Here we tested whether behavioral sensitivity to the neuroactive steroid agonist 5β-pregnan-3α-ol-20-one is altered in genetically engineered mouse models that have deficient GABAA receptor-mediated synaptic inhibition in selected neuro…

Access to new highly potent antileukemia, antiviral and antimalarial agents via hybridization of natural products (homo)egonol, thymoquinone and arte…

2018

Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high pot…

2017

Many quinazoline derivatives have been synthesized over the last few decades with great pharmacological potential, such as antimalarial, anti-inflammatory, antimicrobial, anticancer, and antiviral. But so far, no quinazoline–artemisinin hybrids have been reported in the literature. In the present study, five novel quinazoline–artemisinin hybrids were synthesized and evaluated for their in vitro biological activity against malarial parasites (Plasmodium falciparum 3D7), leukemia cells (CCRF-CEM and CEM/ADR5000), and human cytomegalovirus. Remarkably, hybrid 9 (EC50 = 1.4 nM), the most active antimalarial compound of this study, was not only more potent than artesunic acid (EC50 = 9.7 nM) but…

Conjugative ESBL plasmids differ in their potential to rescue susceptible bacteria via horizontal gene transfer in lethal antibiotic concentrations.

2017

Conjugative ESBL plasmids differ in their potential to rescue susceptible bacteria via horizontal gene transfer in lethal antibiotic concentrations

Small molecule inhibitors and stimulators of inducible nitric oxide synthase in cancer cells from natural origin (phytochemicals, marine compounds, a…

2019

Nitric oxide synthases (NOS) are a family of isoforms, which generate nitric oxide (NO). NO is one of the smallest molecules in nature and acts mainly as a potent vasodilator. It participates in various biological processes ranging from physiological to pathological conditions. Inducible NOS (iNOS, NOS2) is a calcium-independent and inducible isoform. Despite high iNOS expression in many tumors, the role of iNOS is still unclear and complex with both enhancing and prohibiting actions in tumorigenesis. Nature presents a broad variety of natural stimulators and inhibitors, which may either promote or inhibit iNOS response. In the present review, we give an overview of iNOS-modulating agents w…

Atypical 1,4-dihydropyridine derivatives, an approach to neuroprotection and memory enhancement

2016

This mini review is devoted to the design and pharmacological studies of novel atypical 1,4-dihydropyridine (DHP) derivatives which differ to a great extent from the traditional DHPs either by lack of neuronal calcium channel blocking activity and/or inability to protect mitochondrial processes. About 100 new DHP derivatives were screened and the mostly active were selected for detailed studies. The compounds of the series of the amino acid ("free" plus "crypto")-containing DHPs and lipophilic di-cyclic DHPs demonstrated long-lasting neuroprotective and/or memory-enhancing action, particularly at low doses (0.005-0.05mg/kg) in different neurodeficiency rat or mice models, and exerted neurot…

Behavioral fragmentation in the D1CT-7 mouse model of Tourette's syndrome.

2017

Aim The transgenic D1CT-7 mouse is one of the best-characterized animal models of Tourette's syndrome (TS), exhibiting spontaneous tic-like Head-Body Twitches (HBT) and deficits in sensorimotor gating. This study is aimed at evaluating the behavioral dynamics of these mutants and their potential relevance to TS. Methods The behavior of D1CT-7 and Wild Type littermates was firstly assessed by considering frequencies and durations. To detect recurrent real-time behavioral sequences, the multivariate T-pattern analysis was employed. Analyses of transition probabilities among behaviors further provided an overall picture of the behavioral dynamics. Results T-patterns and transition matrices rev…