Considering our previous findings on the remarkable activity exhibited by cobalt(III) with 2-acetylpyridine-
-R-thiosemicarbazone (Hatc-R) compounds against
, the present study aimed to explored new ...structure features of the complexes of the type Co(atc--R)
Cl, where R = methyl (Me,
) or phenyl (Ph,
) (
C NMR, high-resolution mass spectrometry, LC-MS/MS, fragmentation study) together with its antibacterial and antiviral biological activities. The minimal inhibitory and minimal bactericidal concentrations (MIC and MBC) were determined, as well as the antiviral potential of the complexes on chikungunya virus (CHIKV) infection in vitro and cell viability. Co(atc-Ph)
Cl revealed promising MIC and MBC values which ranged from 0.39 to 0.78 µg/mL in two strains tested and presented high potential against CHIKV by reducing viral replication by up to 80%. The results showed that the biological activity is strongly influenced by the peripheral substituent groups at the
(4) position of the atc-R
ligands. In addition, molecular docking analysis was performed. The relative binding energy of the docked compound with five bacteria strains was found in the range of -3.45 and -9.55 kcal/mol. Thus, this work highlights the good potential of cobalt(III) complexes and provide support for future studies on this molecule aiming at its antibacterial and antiviral therapeutic application.
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•Seven Cu(II) complexes with hydrazides and heterocyclic bases were prepared.•Six Cu(II) complexes were evaluated in vitro against T. cruzi.•Two copper complexes were more active than ...benznidazole.•The antichagasic activity of the most promising complex was evaluated in vivo.
In order to improve the previously observed antichagasic activity of Cu(II) complexes containing 2-chlorobenzhydrazide (2-CH), we report herein the synthesis and anti-Trypanosoma cruzi activity of novel copper complexes containing 2-methoxybenzhydrazide (2-MH), 4-methoxybenzhydrazide (4-MH) and three α-diimine ligands, namely, 1,10-phenanthroline (phen), 2,2-bipyridine (bipy) and 4-4′-dimethoxy-2-2′-bipyridine (dmb). Two of these complexes showed higher in vitro anti-Trypanosoma cruzi activity when compared to benznidazole, the main drug used in Chagas disease treatment. One of them, the copper complex with 4-MH and dmb, Cu(4-MH)(dmb)(ClO4)2, exhibited a higher selectivity index than that recommended for preclinical studies. Considering this observation, complex Cu(4-MH)(dmb)(ClO4)2 was selected for preliminary in vivo assays, which verified that this compound was able to reduce parasitemia by 64% at the peak of infection. Further investigations were performed on all compounds. The Cu(II) complexes bind to ct-DNA with Kb values in the range of 103–104 M–1, with Cu(4-MH)(dmb)(ClO4)2 showing the highest Kb value (1.45 × 104 M–1). Molecular docking simulations predicted that Cu(4-MH)(dmb)(ClO4)2 binds in the minor groove of the double helix of ct-DNA and forms one hydrogen bond.
Natural products have been revealed as relevant sources of therapeutic agents including those for the management of pain states. In this study, the anti-nociceptive and anti-inflammatory effects of ...(−)-cassine, isolated from
Senna spectabilis were evaluated using pharmacological, behavioural and biochemical approaches. Oral treatment with (−)-cassine (3–30 mg/kg) reduced carrageenan-induced mechanical and thermal nociception associated with the suppression of myeloperoxidase activity in the mouse paw. Moreover, (−)-cassine (1–10 μg/site) prevented mechanical hyperalgesia induced by carrageenan when given through the intraplantar (i.pl.), spinal and intracerebroventricular routes. Additionally, oral treatment with (−)-cassine (3–60 mg/kg) prevented the mechanical hyperalgesia elicited by intraplantar injection of prostaglandin E
2, complete Freund’s adjuvant, interleukin-1β, interleukin-6 and keratinocyte-derived chemokine. Furthermore, (−)-cassine inhibited the mechanical nociceptive response induced by ligation of the sciatic nerve and also significantly reduced the levels of cytokines/chemokines in paw tissue following i.pl. injection of carrageenan. In addition, the anti-nociceptive and anti-inflammatory actions of (−)-cassine were associated with its ability to interact with both TRPV1 and TRPA1 receptors and by inhibiting the upregulation of cyclooxigenase-2 as well as inhibiting the phosphorylation of MAPK/ERK and the transcription factor NF-κB. It is important to highlight that oral treatment with (−)-cassine did not produce any effects related to temperature, locomotor activity or catalepsy. Altogether, the present data demonstrate that (−)-cassine has systemic, spinal and supraspinal anti-nociceptive properties when assessed in inflammatory and neuropathic pain models. These effects are associated with its ability to block several signalling pathways associated with inflammatory and nociceptive responses.
This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.
► (−)-Cassine is isolated from
Senna spectabilis. ► It inhibits the chronic inflammatory and neuropathic pain in mice. ► Its action is related to reduction of the levels of cytokines IL-1β, KC and IL-6. ► Inhibition of COX-2 activation, MAP-kinases and NF-κB is related to anti-nociceptive actions. ► This compound can be potential drug candidate for pain and inflammation diseases.
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•The characterization of two new polymeric copper(II) complexes bearing 2-chlorobenzhydrazide is reported for first time.•A copper(II) complex has been more active than benznidazole, ...a drug used in the treatment of Chagas disease.•A complex exhibited a good selectivity index.
We report here the characterization of two new polymeric copper(II) complexes containing 2-chlorobenzhydrazide (2-CH) and two N,N-donor ligands, namely, 1,10-phenanthroline (phen) and 4-4′-dimethoxy-2-2′-bipyridine (dmb). The structure of a new polymeric copper(II) complex in which a perchlorate anion acts as a bridge ligand is discussed in detail. In both complexes, spectral data reveals a bidentate coordination mode for hydrazide, perchlorate and N,N-donor ligand. These metal complexes and their free ligands were evaluated for their trypanocidal and cytotoxic activities and the complex with 1,10-phenanthroline has been much more active than benznidazole, a drug used in the treatment of Chagas disease.
The use of natural products has definitely been the most successful strategy in the discovery of novel medicines. Secondary metabolites from terrestrial and marine organisms have found considerable ...use in the treatment of numerous diseases and have been considered lead molecules both in their natural form and as templates for medicinal chemistry. This paper seeks to show the great value of secondary metabolites and emphasize the rich chemical diversity of Brazilian biodiversity. This natural chemical library remains understudied, but can be a useful source of new secondary metabolites with potential application as templates for drug discovery.
The 2-methoxycinnamylidenepyruvic acid (2-MeO-HCP) was synthesized and characterized for nuclear magnetic resonance (1H and 13C NMR), mass spectrometry (MS), Infrared spectroscopy (FTIR) and ...differential scanning calorimetry (DSC). The application of DSC for purity determination is well documented in literature and is used in the analysis of pure organic compounds. The molecular geometry and vibrational frequencies of 2-MeO-HCP have been calculated.
Abstract Introduction 2,6‐Disubstituted piperidin‐3‐ols are an important group of piperidine alkaloids found in species such as Senna spectabilis , whose main constituents include cassine and ...spectaline, compounds with relevant pharmacological activity. The analysis of these compounds is challenging due to the complexity of plant extracts and the absence of chromophores capable of absorbing ultraviolet (UV) radiation. Objective This paper presents a new analytical method to separate and quantify the non‐UV‐absorbing alkaloids present in ethanol extracts from S. spectabilis flowers using capillary zone electrophoresis (CZE) with indirect UV detection. Methodology The optimized CZE method employs a background electrolyte containing 60 mM histidine (His), 15 mM α‐cyclodextrin, 20% acetonitrile (ACN), and pH‐adjusted to 4.7 with acetic acid (AcOH). Results The limit of detection (LOD) values was 10.2 and 13.9 mg L −1 for cassine and spectaline, respectively. For both analytes, the precision data were better than 2% of relative standard deviation (RSD) for migration times and peak areas. To evaluate the applicability of the developed method, ethanolic extracts from S. spectabilis flowers were prepared and analyzed. Conclusions Thereby, the method proved to be efficient and complementary to conventional techniques, offering a cost‐effective alternative in the quantification of the non‐UV‐absorbing piperidine alkaloids present in plant extracts.
A new analytical method for the separation and quantification of two piperidine alkaloids is presented. Cassine and spectaline, compounds with relevant pharmacological activity, were quantified in extracts of Senna spectabilis flowers using capillary zone electrophoresis with indirect UV detection. Both analytes were separated in less than 10 min, and the analytical performance of the method was evaluated using analytical parameters. The method proved to be efficient, offering a cost‐effective alternative in the quantification of the non‐UV‐absorbing piperidine alkaloids in plant extracts.
Introduction
In microbial metabolomics, the use of multivariate data analysis (MDVA) has not been comprehensively explored regarding the different techniques available and the information that each ...gives about the metabolome. To overcome these limitations, here we show the use of
Fusarium oxysporum
cultured in the presence of exogenous alkaloids as a model system to demonstrate a comprehensive strategy for metabolic profiling.
Matherials and methods
F. oxysporum
was harvested on different days of incubation after alkaloidal addition, and the chemical profiles were compared using LC–MS data and MDVA. We show significant innovation to evaluate the chemical production of microbes during their life cycle by utilizing the full capabilities of Partial Least Square (PLS) with microbial-specific modeling that considers incubation days, media culture availability, and growth rate in solid media.
Results and Discusscion
Results showed that the treatment of the Y-data and the use of both PLS regression and discrimination (PLSr and PLS-DA) inferred complemental chemical information. PLSr revealed the metabolites that are produced/consumed during fungal growth, whereas PLS-DA focused on metabolites that are only consumed/produced at a specific period. Both regression and classificatory analysis were equally important to identify compounds that are regulated and/or selectively produced as a response to the presence of the alkaloids. Lastly, we report the annotation of analogs from the piperidine alkaloids biotransformed by
F. oxysporum
as a defense response to the toxic plant metabolites. These molecules do not show the antimicrobial potential of their precursors in the fungal extracts and were rapidly produced and consumed within 4 days of microbial growth.
As part of our ongoing research on antifungal agents from Brazilian flora, eight extracts and twelve fractions from Pterogyne nitens Tul., Fabaceae, were screened for antimicrobial activity against ...four opportunistic fungi species (Candida albicans, Candida krusei, Candida parapsilosis and Cryptococcus neoformans) using a broth microdilution method. The present investigation reveals that P. nitens extracts and fractions were more effective against C. krusei and C. parapsilosis than against C. neoformans. The growth of C. albicans was moderately affected by all tested extracts and fractions. The strongest effects were observed for n-butanol fractions from branches (MIC = 15.6 μg/mL) and roots (MIC = 31.2 μg/mL) against C. krusei. Additionally, the chromatographic fractionation of the n-butanol fraction from branches afforded four guanidine alkaloids; N-1,N-2,N-3-triisopentenylguanidine (1), described for the first time in the Fabaceae family, and nitensidines A-C (2-4), which showed moderate activity towards C. krusei (MIC = 62.5 μg/mL) and C. parapsilosis (MIC = 31.2 μg/mL).
Natural products are the inspiration for many valuable therapeutic agents and attest to biodiversity being a rich source of new molecular structures. Their value as templates for medicinal chemistry ...remains undisputed, even after the growth of the combinatorial chemistry era. Tropical environments, such as Brazilian biomes, offer a particularly rich potential for biologically active compounds with unique structures and continue to contribute toward modern drug discovery. Our bioprospecting of plant species of the
and Atlantic Forest biomes has yielded promising bioactive secondary metabolites, and we describe some of these molecules and semisynthetic derivatives as potential acetylcholinesterase (AChE) inhibitors.
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