Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 41
Filter
Add more filters










Publication year range
1.
J Pharm Pract ; 36(4): 953-966, 2023 Aug.
Article in English | MEDLINE | ID: mdl-35723017

ABSTRACT

SARS-CoV-2 causes the highly contagious coronavirus disease (COVID-19), first discovered in Wuhan, China, in December of 2019. As of August 21, 2021, over 211 million people have been diagnosed with COVID-19 and 4.42 million people have died from the disease worldwide. The COVID-19 pandemic has adversely affected world economies, global public health infrastructure, and social behaviors. Despite physical distancing and the advent of symptomatic and monoclonal antibody therapies, perhaps the most effective method to combat COVID-19 remains the creation of immunity through vaccines. Scientific communities globally have been diligently working to develop vaccines since the start of the pandemic. Though a few have been authorized for use, the Pfizer vaccine was the first to be given full approval in the United States in August 2021 - being the quickest vaccine to ever be developed. Although several vaccines produced via different approaches are in use, no mortality has been reported thus far from vaccine use. Here, we highlight the latest advances in the development of the COVID-19 vaccines, specifically the lead candidates that are in late-stage clinical trials or authorized for emergency use. As SARS-CoV-2 uses its spike protein to enter a host cell and cause infection, most vaccine candidates target this protein. This review describes the various COVID-19 vaccines - authorized and/or under development - and their composition, advantages, and potential limitations as the world continues to fight this devastating pandemic.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19 Vaccines/therapeutic use , Pandemics/prevention & control , COVID-19/prevention & control , SARS-CoV-2 , Vaccination
2.
Biomedicines ; 8(8)2020 Aug 11.
Article in English | MEDLINE | ID: mdl-32796613

ABSTRACT

Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (p < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3ßHSD (p < 0.001), 17ßHSD (p < 0.001), CYP17A (p < 0.01), SRB1 (p < 0.0001), and StAR (p < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (p < 0.001). Genistein caused similar decreases in the expression of 17ßHSD and CYP17A (2.5-fold (p < 0.001) and 1.5-fold decrease (p < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3ßHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted.

3.
Plant Signal Behav ; 13(3): e1449544, 2018 03 04.
Article in English | MEDLINE | ID: mdl-29521550

ABSTRACT

Aldehyde dehydrogenase enzymes (ALDHs) catalyse the oxidation of a broad range of aliphatic and aromatic aldehydes to their corresponding carboxylic acids using NAD+ or NADP+ as cofactors. In our article published in Scientific Reports, we demonstrated that mutations in Arabidopsis ALDH3I1 and ALDH7B4 genes altered the cellular contents of NAD(P)H, the total as well as the reduction state of glutathione; and decreased the efficiency of photosynthesis, thus placing ALDH activity as an important source of reducing power for cellular redox homeostasis. Our results also revealed that the ALDHs contribute to the reducing power required for the nitrate assimilation. Here, we discussed and elucidated the innovative hypothesis of the glycolaldehyde shunt pathway of photorespiration that would involve ALDHs generating in contrast to the known core photorespiration reactions, a net gain of two moles of NAD(P)H to support nitrate assimilation, glutathione homeostasis and ROS detoxification.


Subject(s)
Acetaldehyde/analogs & derivatives , Aldehyde Dehydrogenase/metabolism , Light , Acetaldehyde/metabolism , Cell Respiration/radiation effects , Models, Biological
4.
Sci Rep ; 8(1): 2936, 2018 02 13.
Article in English | MEDLINE | ID: mdl-29440669

ABSTRACT

Aldehyde dehydrogenase enzymes (ALDHs) catalyze the oxidation of aliphatic and aromatic aldehydes to their corresponding carboxylic acids using NAD+ or NADP+ as cofactors and generating NADH or NADPH. Previous studies mainly focused on the ALDH role in detoxifying toxic aldehydes but their effect on the cellular NAD(P)H contents has so far been overlooked. Here, we investigated whether the ALDHs influence the cellular redox homeostasis. We used a double T-DNA insertion mutant that is defective in representative members of Arabidopsis thaliana ALDH families 3 (ALDH3I1) and 7 (ALDH7B4), and we examined the pyridine nucleotide pools, glutathione content, and the photosynthetic capacity of the aldh mutants in comparison with the wild type. The loss of function of ALDH3I1 and ALDH7B4 led to a decrease of NAD(P)H, NAD(P)H/NAD(P) ratio, and an alteration of the glutathione pools. The aldh double mutant had higher glucose-6-phosphate dehydrogenase activity than the wild type, indicating a high demand for reduced pyridine nucleotides. Moreover, the mutant had a reduced quantum yield of photosystem II and photosynthetic capacity at relatively high light intensities compared to the wild type. Altogether, our data revealed a role of ALDHs as major contributors to the homeostasis of pyridine nucleotides in plants.


Subject(s)
Aldehyde Dehydrogenase/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Homeostasis , NADP/metabolism , NAD/metabolism , Aldehyde Dehydrogenase/deficiency , Aldehyde Dehydrogenase/genetics , Arabidopsis/enzymology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Gene Knockout Techniques , Photosynthesis
5.
Data Brief ; 9: 1039-1043, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27900358

ABSTRACT

This article reports data on four carbazones of piperitone: semicarbazone 1, thiosemicarbazone 2, 4-phenyl semicarbazone 3 and 4-phenyl thiosemicarbazone 4 prepared directly in situ from essential oil of Cymbopogon schoenantus, whose GC-FID and GC-MS analysis revealed piperitone as major component (68.20%). The structures of hemi-synthesized compounds were confirmed by high throughput IR, MS, 1H and 13C NMR based spectrometric analysis. Their antiparasitic activities were evaluated in vitro on Trypanosoma brucei brucei (Tbb). The compound 3 (IC50=8.63±0.81 µM) and 4 (IC50=10.90±2.52 µM) exhibited antitrypanosomal activity, 2 had a moderate activity (IC50=74.58±4.44 µM) but 1 was void of significant activity (IC50=478.47 µM). The in vitro tests showed that all compounds were less cytotoxic against the human non cancer fibroblast cell line (WI38) (IC50>80 µM) while only 2 (IC50=21.16±1.37 µM) and 4 (IC50=32.22±1.66 µM) were cytotoxic against the Chinese Hamster Ovary (CHO) cells and toxic on Artemia salina (Leach) larvae. Piperitone 4-phenyl semicarbazone 3, the best antitrypanosomal compound, showed also a selectivity index (SI) higher than 7 on the larvae and the tested cells and therefore might be further studied as antitrypanosomal agent. Also, all compounds except 3 showed selectivity between the two tested cell lines (SI>2). This data reveals for the first time the antitrypinosomal properties of thiosemicarbazones, their cytotoxicity on mammalian cells as well as their activities against Tbb and A. salina Leach.

6.
PLoS One ; 11(10): e0165867, 2016.
Article in English | MEDLINE | ID: mdl-27798665

ABSTRACT

Plant aldehyde dehydrogenases (ALDHs) play important roles in cell wall biosynthesis, growth, development, and tolerance to biotic and abiotic stresses. The Reduced Epidermal Fluorescence1 is encoded by the subfamily 2C of ALDHs and was shown to oxidise coniferaldehyde and sinapaldehyde to ferulic acid and sinapic acid in the phenylpropanoid pathway, respectively. This knowledge has been gained from works in the dicotyledon model species Arabidopsis thaliana then used to functionally annotate ALDH2C isoforms in other species, based on the orthology principle. However, the extent to which the ALDH isoforms differ between monocotyledons and dicotyledons has rarely been accessed side-by-side. In this study, we used a phylogenetic approach to address this question. We have analysed the ALDH genes in Brachypodium distachyon, alongside those of other sequenced monocotyledon and dicotyledon species to examine traits supporting either a convergent or divergent evolution of the ALDH2C/REF1-type proteins. We found that B. distachyon, like other grasses, contains more ALDH2C/REF1 isoforms than A. thaliana and other dicotyledon species. Some amino acid residues in ALDH2C/REF1 isoforms were found as being conserved in dicotyledons but substituted by non-equivalent residues in monocotyledons. One example of those substitutions concerns a conserved phenylalanine and a conserved tyrosine in monocotyledons and dicotyledons, respectively. Protein structure modelling suggests that the presence of tyrosine would widen the substrate-binding pocket in the dicotyledons, and thereby influence substrate specificity. We discussed the importance of these findings as new hints to investigate why ferulic acid contents and cell wall digestibility differ between the dicotyledon and monocotyledon species.


Subject(s)
Aldehyde Dehydrogenase/chemistry , Aldehyde Dehydrogenase/genetics , Catalytic Domain , Plant Proteins/chemistry , Plant Proteins/genetics , Amino Acid Sequence , Amino Acid Substitution , Base Composition , Base Sequence , Brachypodium/genetics , Catalysis , Catalytic Domain/genetics , Codon , Isoenzymes , Models, Molecular , Multigene Family , Phylogeny , Protein Conformation
7.
PLoS One ; 11(10): e0164798, 2016.
Article in English | MEDLINE | ID: mdl-27755582

ABSTRACT

Aldehyde dehydrogenases (ALDHs) is a protein superfamily that catalyzes the oxidation of aldehyde molecules into their corresponding non-toxic carboxylic acids, and responding to different environmental stresses, offering promising genetic approaches for improving plant adaptation. The aim of the current study is the functional analysis for systematic identification of S. lycopersicum ALDH gene superfamily. We performed genome-based ALDH genes identification and functional classification, phylogenetic relationship, structure and catalytic domains analysis, and microarray based gene expression. Twenty nine unique tomato ALDH sequences encoding 11 ALDH families were identified, including a unique member of the family 19 ALDH. Phylogenetic analysis revealed 13 groups, with a conserved relationship among ALDH families. Functional structure analysis of ALDH2 showed a catalytic mechanism involving Cys-Glu couple. However, the analysis of ALDH3 showed no functional gene duplication or potential neo-functionalities. Gene expression analysis reveals that particular ALDH genes might respond to wounding stress increasing the expression as ALDH2B7. Overall, this study reveals the complexity of S. lycopersicum ALDH gene superfamily and offers new insights into the structure-functional features and evolution of ALDH gene families in vascular plants. The functional characterization of ALDHs is valuable and promoting molecular breeding in tomato for the improvement of stress tolerance and signaling.


Subject(s)
Aldehyde Dehydrogenase/genetics , Genome, Plant , Plant Proteins/genetics , Solanum lycopersicum/genetics , Aldehyde Dehydrogenase/chemistry , Aldehyde Dehydrogenase/classification , Aldehyde Dehydrogenase/metabolism , Binding Sites , Biocatalysis , Coenzymes/chemistry , Coenzymes/metabolism , Gene Expression Regulation, Plant , Hydrogen Bonding , Ligands , Solanum lycopersicum/metabolism , Molecular Dynamics Simulation , Multigene Family , Oligonucleotide Array Sequence Analysis , Phylogeny , Plant Proteins/chemistry , Plant Proteins/classification , Plant Proteins/metabolism , Protein Structure, Tertiary , Stress, Physiological
8.
J Basic Microbiol ; 56(2): 153-61, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26627705

ABSTRACT

The efficacy of a rhizobacterium Streptomyces aurantiogriseus VSMGT1014 for the production of bioactive metabolites with antifungal properties was evaluated under in vitro conditions. The production of bioactive metabolites by S. aurantiogriseus VSMGT1014 in International Streptomyces Project-2 (ISP-2) broth, supplemented with glucose and ammonium acetate was found to be the most suitable carbon and nitrogen sources for the maximum production of bioactive metabolites against rice pathogen, Rhizoctonia solani. The zone of inhibition range from 23.5 to 28.5 mm and 10.3 to 18.3 mm for glucose and ammonium acetate supplemented media, respectively. The culture filtrate of S. aurantiogriseus VSMGT1014 at pH 7.5, 37 °C at 120 rpm in 6 days of incubation showed the maximum production of bioactive metabolites with antagonistic potential. The crude metabolite was characterized by different spectral studies such as Ultraviolet spectrum, infrared-spectrum and based on the different analytical techniques, including thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) with the retention time 29.4 and the bioactive metabolite was identified as phenazine, which was confirmed by pure phenazine compound as positive control.


Subject(s)
Antifungal Agents/metabolism , Oryza/microbiology , Phenazines/metabolism , Plant Diseases/microbiology , Rhizoctonia/drug effects , Streptomyces/metabolism , Acetates/metabolism , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Culture Media/chemistry , Glucose/metabolism , Phenazines/chemistry , Phenazines/isolation & purification , Spectrum Analysis , Temperature
9.
Biochem Res Int ; 2015: 493879, 2015.
Article in English | MEDLINE | ID: mdl-25767723

ABSTRACT

Kola nut is chewed in many West African cultures and is used ceremonially. The aim of this study is to investigate some biological effects of Cola nitida's bark after phytochemical screening. The bark was collected, dried, and then powdered for the phytochemical screening and extractions. Ethanol and ethyl acetate extracts of C. nitida were used in this study. The antibacterial activity was tested on ten reference strains and 28 meat isolated Staphylococcus strains by disc diffusion method. The antifungal activity of three fungal strains was determined on the Potato-Dextrose Agar medium mixed with the appropriate extract. The antioxidant activity was determined by DPPH and ABTS methods. Our data revealed the presence of various potent phytochemicals. For the reference and meat isolated strains, the inhibitory diameter zone was from 17.5 ± 0.7 mm (C. albicans) to 9.5 ± 0.7 mm (P. vulgaris). The MIC ranged from 0.312 mg/mL to 5.000 mg/mL and the MBC from 0.625 mg/mL to >20 mg/mL. The highest antifungal activity was observed with F. verticillioides and the lowest one with P. citrinum. The two extracts have an excellent reducing free radical activity. The killing effect of A. salina larvae was perceptible at 1.04 mg/mL. The purified extracts of Cola nitida's bark can be used to hold meat products and also like phytomedicine.

10.
World J Microbiol Biotechnol ; 30(12): 3149-61, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25304022

ABSTRACT

A total of 132 actinomycetes was isolated from different rice rhizosphere soils of Tamil Nadu, India, among which 57 showed antagonistic activity towards Rhizoctonia solani, which is sheath blight (ShB) pathogen of rice and other fungal pathogens such as Macrophomina phaseolina, Fusarium oxysporum, Fusarium udum and Alternaria alternata with a variable zone of inhibition. Potential actinomycete strain VSMGT1014 was identified as Streptomyces aurantiogriseus VSMGT1014 based on the morphological, physiological, biochemical and 16S rRNA sequence analysis. The strain VSMGT1014 produced lytic enzymes, secondary metabolites, siderophore, volatile substance and indole acetic acid. Crude metabolites of VSMGT1014 showed activity against R. solani at 5 µg ml(-1); however, the prominent inhibition zone was observed from 40 to 100 µg ml(-1). Reduced lesion heights observed in culture, cells-free filtrate, crude metabolites and carbendazim on challenge with pathogen in the detached leaf assay. The high content screening test clearly indicated denucleation of R. solani at 5 µg ml(-1) treatment of crude metabolite and carbendazim respectively. The results conclude that strain VSMGT1014 was found to be a potential candidate for the control of ShB of rice as a bio fungicide.


Subject(s)
Antibiosis , Fungi/growth & development , Plant Diseases/prevention & control , Soil Microbiology , Streptomyces/physiology , Antifungal Agents/metabolism , Biological Products/metabolism , Cluster Analysis , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , India , Molecular Sequence Data , Oryza , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Streptomyces/classification , Streptomyces/genetics , Streptomyces/isolation & purification
11.
Plant Physiol ; 166(3): 1312-28, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25201878

ABSTRACT

The actin cytoskeleton is a major regulator of cell morphogenesis and responses to biotic and abiotic stimuli. The organization and activities of the cytoskeleton are choreographed by hundreds of accessory proteins. Many actin-binding proteins are thought to be stimulus-response regulators that bind to signaling phospholipids and change their activity upon lipid binding. Whether these proteins associate with and/or are regulated by signaling lipids in plant cells remains poorly understood. Heterodimeric capping protein (CP) is a conserved and ubiquitous regulator of actin dynamics. It binds to the barbed end of filaments with high affinity and modulates filament assembly and disassembly reactions in vitro. Direct interaction of CP with phospholipids, including phosphatidic acid, results in uncapping of filament ends in vitro. Live-cell imaging and reverse-genetic analyses of cp mutants in Arabidopsis (Arabidopsis thaliana) recently provided compelling support for a model in which CP activity is negatively regulated by phosphatidic acid in vivo. Here, we used complementary biochemical, subcellular fractionation, and immunofluorescence microscopy approaches to elucidate CP-membrane association. We found that CP is moderately abundant in Arabidopsis tissues and present in a microsomal membrane fraction. Sucrose density gradient separation and immunoblotting with known compartment markers were used to demonstrate that CP is enriched on membrane-bound organelles such as the endoplasmic reticulum and Golgi. This association could facilitate cross talk between the actin cytoskeleton and a wide spectrum of essential cellular functions such as organelle motility and signal transduction.


Subject(s)
Actin Capping Proteins/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Cell Membrane/metabolism , Actin Capping Proteins/genetics , Actin Cytoskeleton/metabolism , Arabidopsis Proteins/genetics , Cytoplasm/metabolism , Endoplasmic Reticulum/metabolism , Gene Knockdown Techniques , Golgi Apparatus/metabolism , Microsomes/metabolism , Molecular Sequence Data , Seedlings/genetics , Seedlings/metabolism
12.
BMC Plant Biol ; 14: 221, 2014 Aug 27.
Article in English | MEDLINE | ID: mdl-25158860

ABSTRACT

BACKGROUND: A molecular-level understanding of the loss of CURVY1 (CVY1) gene expression (which encodes a member of the receptor-like protein kinase family) was investigated to gain insights into the mechanisms controlling cell morphogenesis and development in Arabidopsis thaliana. RESULTS: Using a reverse genetic and cell biology approaches, we demonstrate that CVY1 is a new DISTORTED gene with similar phenotypic characterization to previously characterized ARP2/3 distorted mutants. Compared to the wild type, cvy1 mutant displayed a strong distorted trichome and altered pavement cell phenotypes. In addition, cvy1 null-mutant flowers earlier, grows faster and produces more siliques than WT and the arp2/3 mutants. The CVY1 gene is ubiquitously expressed in all tissues and seems to negatively regulate growth and yield in higher plants. CONCLUSIONS: Our results suggest that CURVY1 gene participates in several biochemical pathways in Arabidopsis thaliana including (i) cell morphogenesis regulation through actin cytoskeleton functional networks, (ii) the transition of vegetative to the reproductive stage and (iii) the production of seeds.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/physiology , Flowers/physiology , Plant Development/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Cell Surface/genetics , Seeds/growth & development , Actins/metabolism , Arabidopsis/cytology , Arabidopsis Proteins/metabolism , Cell Wall/metabolism , Genes, Plant , Morphogenesis , Phenotype , Protein Serine-Threonine Kinases/metabolism , Receptors, Cell Surface/metabolism , Signal Transduction , Trichomes/growth & development
13.
Biomed Res Int ; 2014: 485620, 2014.
Article in English | MEDLINE | ID: mdl-24987686

ABSTRACT

The aim of our study was to investigate the microbial quality of meat products and on some clinical samples in Abidjan focused on Staphylococcus genus and the toxin production profile of Staphylococcus aureus (S. aureus) isolated. Bacteria were collected from 240 samples of three meat products sold in Abidjan and 180 samples issued from clinical infections. The strains were identified by both microbiological and MALDI-TOF-MS methods. The susceptibility to antibiotics was determined by the disc diffusion method. The production of Panton-Valentine Leukocidin, LukE/D, and epidermolysins was screened using radial gel immunodiffusion. The production of staphylococcal enterotoxins and TSST-1 was screened by a Bio-Plex Assay. We observed that 96/240 of meat samples and 32/180 of clinical samples were contaminated by Staphylococcus. Eleven species were isolated from meats and 4 from clinical samples. Forty-two S. aureus strains were isolated from ours samples. Variability of resistance was observed for most of the tested antibiotics but none of the strains displays a resistance to imipenem and quinolones. We observed that 89% of clinical S. aureus were resistant to methicillin against 58% for those issued from meat products. All S. aureus isolates issued from meat products produce epidermolysins whereas none of the clinical strains produced these toxins. The enterotoxins were variably produced by both clinical and meat product samples.


Subject(s)
Antigens, Bacterial/biosynthesis , Bacterial Toxins/biosynthesis , Food Microbiology , Mass Spectrometry , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/metabolism , Humans , Species Specificity
14.
Mol Biol Rep ; 41(8): 5199-206, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24802797

ABSTRACT

African sorghum opaque beers play a vital role in the diet of millions of consumers. In the current study we investigated the growth profiles of yeast strains isolated from kpete-kpete, a traditional starter used to produce tchoukoutou, an opaque sorghum beer in Benin. 10 yeast strains were isolated from sorghum beer starters and cultivated under both liquid and solid media for phenotypic growth characterization. All yeast isolates were able to grow both on solid and liquid media. Based on their growth profiles, the isolates were clustered into three groups: (i) the aggressive growth pattern (30%), (ii) the moderate growth pattern (50%), and (iii) the slow growth pattern (20%). Based on gene expression pattern, absorbance (A(600 nm)) and diameter of growth in both liquid and solid media respectively, yeast strains YK34, YK15 and YK48 were clustered in the first group, and referred to as the most aggressive growth strains, followed by group 2 (YK24, YK5, YK12, YK20, YK2) and group 3 (YK37, YK41). This growth pattern was confirmed by Invertase gene expression profiling of the yeasts showing group 1 with high level of Invertase gene expression followed by group 2 and group 3 respectively. Our results suggest that YK34, YK15 and YK48 and YK2 yeast strains constitute the best candidates in fermentation of sorghum beer production based on growth rate and assimilation of carbon and nitrogen sources.


Subject(s)
Candida/isolation & purification , DNA, Fungal/isolation & purification , Saccharomyces cerevisiae/isolation & purification , Beer/microbiology , Candida/classification , Candida/genetics , Candida/growth & development , DNA, Fungal/genetics , Fermentation , Food Handling , Food Microbiology , Phenotype , Saccharomyces cerevisiae/classification , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Sorghum/chemistry , Transcriptome
15.
Mol Biol Rep ; 41(3): 1617-22, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24407605

ABSTRACT

Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1-5). Their structures were characterized by spectrometrical methods analysis IR, NMR (1)H & (13)C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC50) equal to 2.76, 2.83, 3.86 and 8.48 µM respectively, while compound 5 (IC50 = 12.16 µM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC50 >281 µM, the others exerted toxic effect on larvae with LC50 of 5.56, 13.62, 14.55 and 42.50 µM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI >1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2-5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.


Subject(s)
Artemia/drug effects , Thiosemicarbazones/pharmacology , Trypanosoma brucei brucei/drug effects , Trypanosomiasis, African/drug therapy , Animals , Humans , Thiosemicarbazones/chemical synthesis , Trypanosoma brucei brucei/pathogenicity , Trypanosomiasis, African/parasitology , Trypanosomiasis, African/pathology
16.
BMC Plant Biol ; 14: 37, 2014 Jan 27.
Article in English | MEDLINE | ID: mdl-24467952

ABSTRACT

BACKGROUND: WD40 domains have been found in a plethora of eukaryotic proteins, acting as scaffolding molecules assisting proper activity of other proteins, and are involved in multi-cellular processes. They comprise several stretches of 44-60 amino acid residues often terminating with a WD di-peptide. They act as a site of protein-protein interactions or multi-interacting platforms, driving the assembly of protein complexes or as mediators of transient interplay among other proteins. In Arabidopsis, members of WD40 protein superfamily are known as key regulators of plant-specific events, biologically playing important roles in development and also during stress signaling. RESULTS: Using reverse genetic and protein modeling approaches, we characterize GIGANTUS1 (GTS1), a new member of WD40 repeat protein in Arabidopsis thaliana and provide evidence of its role in controlling plant growth development. GTS1 is highly expressed during embryo development and negatively regulates seed germination, biomass yield and growth improvement in plants. Structural modeling analysis suggests that GTS1 folds into a ß-propeller with seven pseudo symmetrically arranged blades around a central axis. Molecular docking analysis shows that GTS1 physically interacts with two ribosomal protein partners, a component of ribosome Nop16, and a ribosome-biogenesis factor L19e through ß-propeller blade 4 to regulate cell growth development. CONCLUSIONS: Our results indicate that GTS1 might function in plant developmental processes by regulating ribosomal structural features, activities and biogenesis in plant cells. Our results suggest that GIGANTUS1 might be a promising target to engineer transgenic plants with higher biomass and improved growth development for plant-based bioenergy production.


Subject(s)
Arabidopsis/embryology , Arabidopsis/metabolism , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Biomass , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Germination/physiology , Ribosomes/metabolism , Seeds/embryology , Seeds/metabolism , Seeds/physiology
17.
J Comput Aided Mol Des ; 27(10): 873-95, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24154826

ABSTRACT

Isoflavone reductase-like proteins (IRLs) are enzymes with key roles in the metabolism of diverse flavonoids. Last identified olive pollen allergen (Ole e 12) is an IRL relevant for allergy amelioration, since it exhibits high prevalence among atopic patients. The goals of this study are the characterization of (A) the structural-functionality of Ole e 12 with a focus in its catalytic mechanism, and (B) its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering (1) physicochemical properties and functional-regulatory motifs, (2) sequence analysis, 2-D and 3D structural homology modeling comparative study and molecular docking, (3) conservational and evolutionary analysis, (4) catalytic mechanism modeling, and (5) sequence, structure-docking based B-cell epitopes prediction, while T-cell epitopes were predicted by inhibitory concentration and binding score methods. Structural-based detailed features, phylogenetic and sequences analysis have identified Ole e 12 as phenylcoumaran benzylic ether reductase. A catalytic mechanism has been proposed for Ole e 12 which display Lys133 as one of the conserved residues of the IRLs catalytic tetrad (Asn-Ser-Tyr-Lys). Structure characterization revealed a conserved protein folding among plants IRLs. However, sequence polymorphism significantly affected residues involved in the catalytic pocket structure and environment (cofactor and substrate interaction-recognition). It might also be responsible for IRLs isoforms functionality and regulation, since micro-heterogeneities affected physicochemical and posttranslational motifs. This polymorphism might have large implications for molecular differences in B- and T-cells epitopes of Ole e 12, and its identification may help designing strategies to improve the component-resolving diagnosis and immunotherapy of pollen and food allergy through development of molecular tools.


Subject(s)
Allergens/immunology , Epitopes/genetics , Oxidoreductases/chemistry , Oxidoreductases/immunology , Allergens/chemistry , Amino Acid Sequence , Catalysis , Catalytic Domain , Cloning, Molecular , Epitopes/chemistry , Epitopes/immunology , Humans , Models, Molecular , Olea/enzymology , Olea/immunology , Oxidoreductases/metabolism , Phylogeny , Pollen/enzymology , Pollen/immunology , Sequence Homology, Amino Acid , Structure-Activity Relationship
18.
BMC Microbiol ; 13: 188, 2013 Aug 08.
Article in English | MEDLINE | ID: mdl-23924370

ABSTRACT

BACKGROUND: Staphylococcus aureus is an opportunistic commensal bacterium that mostly colonizes the skin and soft tissues. The pathogenicity of S. aureus is due to both its ability to resist antibiotics, and the production of toxins. Here, we characterize a group of genes responsible for toxin production and antibiotic resistance of S. aureus strains isolated from skin, soft tissue, and bone related infections. RESULTS: A total of 136 S. aureus strains were collected from five different types of infection: furuncles, pyomyositis, abscesses, Buruli ulcers, and osteomyelitis, from hospital admissions and out-patients in Benin. All strains were resistant to benzyl penicillin, while 25% were resistant to methicillin, and all showed sensitivity to vancomycin. Panton-Valentine leukocidin (PVL) was the most commonly produced virulence factor (70%), followed by staphylococcal enterotoxin B (44%). Exfoliative toxin B was produced by 1.3% of the strains, and was only found in isolates from Buruli ulcers. The tsst-1, sec, and seh genes were rarely detected (≤1%). CONCLUSIONS: This study provides new insight into the prevalence of toxin and antibiotic resistance genes in S. aureus strains responsible for skin, soft tissue, and bone infections. Our results showed that PVL was strongly associated with pyomyositis and osteomyelitis, and that there is a high prevalence of PVL-MRSA skin infections in Benin.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Toxins/metabolism , Bone Diseases/microbiology , Soft Tissue Infections/microbiology , Staphylococcal Infections/microbiology , Staphylococcal Skin Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism , Bacterial Proteins/genetics , Humans , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification
19.
BMC Plant Biol ; 13: 79, 2013 May 14.
Article in English | MEDLINE | ID: mdl-23672620

ABSTRACT

BACKGROUND: ANGUSTIFOLIA (AN), one of the CtBP family proteins, plays a major role in microtubule-dependent cell morphogenesis. Microarray analysis of mammalian AN homologs suggests that AN might function as a transcriptional activator and regulator of a wide range of genes. Genetic characterization of AN mutants suggests that AN might be involved in multiple biological processes beyond cell morphology regulation. RESULTS: Using a reverse genetic approach, we provide in this paper the genetic, biochemical, and physiological evidence for ANGUSTIFOLIA's role in other new biological functions such as abiotic and biotic stress response in higher plants. The T-DNA knockout an-t1 mutant exhibits not only all the phenotypes of previously described angustifolia null mutants, but also copes better than wild type under dehydration and pathogen attack. The stress tolerance is accompanied by a steady-state modulation of cellular H(2)O(2) content, malondialdehyde (MDA) derived from cellular lipid peroxidation, and over-expression of stress responsive genes. Our results indicate that ANGUSTIFOLIA functions beyond cell morphology control through direct or indirect functional protein interaction networks mediating other biological processes such as drought and pathogen attacks. CONCLUSIONS: Our results indicate that the ANGUSTIFOLIA gene participates in several biochemical pathways controlling cell morphogenesis, abiotic, and biotic stress responses in higher plants. Our results suggest that the in vivo function of plant ANGUSTIFOLIA has been overlooked and it needs to be further studied beyond microtubule-dependent cell morphogenesis.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Repressor Proteins/metabolism , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis/microbiology , Arabidopsis Proteins/genetics , Droughts , Gene Expression Regulation, Plant , Hydrogen Peroxide/metabolism , Morphogenesis , Oxidative Stress , Plant Diseases/microbiology , Pseudomonas syringae/physiology , Repressor Proteins/genetics , Stress, Physiological
20.
Plant Physiol ; 162(2): 689-706, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23613272

ABSTRACT

During plant cell morphogenesis, signal transduction and cytoskeletal dynamics interact to locally organize the cytoplasm and define the geometry of cell expansion. The WAVE/SCAR (for WASP family verprolin homologous/suppressor of cyclic AMP receptor) regulatory complex (W/SRC) is an evolutionarily conserved heteromeric protein complex. Within the plant kingdom W/SRC is a broadly used effector that converts Rho-of-Plants (ROP)/Rac small GTPase signals into Actin-Related Protein2/3 and actin-dependent growth responses. Although the components and biochemistry of the W/SRC pathway are well understood, a basic understanding of how cells partition W/SRC into active and inactive pools is lacking. In this paper, we report that the endoplasmic reticulum (ER) is an important organelle for W/SRC regulation. We determined that a large intracellular pool of the core W/SRC subunit NAP1, like the known positive regulator of W/SRC, the DOCK family guanine nucleotide-exchange factor SPIKE1 (SPK1), localizes to the surface of the ER. The ER-associated NAP1 is inactive because it displays little colocalization with the actin network, and ER localization requires neither activating signals from SPK1 nor a physical association with its W/SRC-binding partner, SRA1. Our results indicate that in Arabidopsis (Arabidopsis thaliana) leaf pavement cells and trichomes, the ER is a reservoir for W/SRC signaling and may have a key role in the early steps of W/SRC assembly and/or activation.


Subject(s)
Adenosine Triphosphatases/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Endoplasmic Reticulum/metabolism , Plant Leaves/metabolism , Actins/metabolism , Adenosine Triphosphatases/genetics , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Endoplasmic Reticulum/genetics , Intracellular Membranes/metabolism , Multiprotein Complexes/metabolism , Plant Leaves/genetics , Plants, Genetically Modified , Signal Transduction , Trichomes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...