Synthesis,characterization, and anticancer evaluation of novel 4-hydrazinothiazole analogs

Single-step synthesis of novel 4-hydrazinothiazole derivatives 6a–e was achieved under mild conditions using the sequential four-components method involving isothiocyanate, aminoguanidine, carbonyl adduct, and α-haloketone derivatives. Deprotection of these hydrazinothiazoles was influenced by acylation, providing a novel group of diacylated molecular structures with a broader scope for the design of thiazolyl-containing drugs 7a and 7b . FTIR, ¹H/¹³C NMR, LC–MS spectroscopy, and CHN elemental analyses were used to study the compound chemical structures. Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human periodontal ligament fibroblast (HPDLF) cells, the 4-hydrazinothiazole derivatives were screened for cytotoxicity in an in vitro cytotoxicity investigation. The 4-hydrazinothiazole compound 6b bearing an isopropylidene-hydrazino group demonstrated strongly potent cytotoxicity against CAKI1 (IC₅₀ = 1.65 ± 0.24 μM) and A498 (IC₅₀ of 0.85 ± 0.24 μM). Furthermore, the chloroacetyl-containing thiazole compound 7a displayed efficient inhibition of growth against the test cell lines CAKI1 and A498 at low micromolar concentrations, IC₅₀ 0.78 and 0.74 μM, respectively.     

Validated spectrofluorimetric assay of two co-administered drug mixtures containing hydroxychloroquine with either moxifloxacin or ofloxacin as a drug regimen for hospital-acquired pneumonia in patients with COVID-19

Moxifloxacin and ofloxacin are two broad-spectrum quinolone antibiotics. They are among the most widely used antibiotics, at this time, applied to control the COVID-19 pandemic. Hydroxychloroquine is an FDA-approved drug for the treatment of COVID-19. This work describes a simple, green, selective, and sensitive spectrofluorimetric method for the assay of moxifloxacin and ofloxacin in the presence of hydroxychloroquine, two co-administered mixtures used in the treatment of hospital-acquired pneumonia in patients with COVID-19. Simultaneous assay of hydroxychloroquine and moxifloxacin was carried out in methanol using a direct spectrofluorimetric method (method I) at 375 and 550 nm, respectively, after excitation at 300 nm. The direct spectrofluorimetric assay was rectilinear over concentration ranges 50.0–400.0 and 300.0–2500.0 ng/ml for hydroxychloroquine and moxifloxacin, respectively, with limits of detection (LOD) of 6.4 and 33.64 ng/ml and limits of quantitation (LOQ) of 19.4 and 102.6 ng/ml, respectively, for the two drugs. The assay for hydroxychloroquine and ofloxacin was carried out by measuring the first derivative synchronous amplitude for hydroxychloroquine at the zero crossing point of ofloxacin and vice versa at Δλ = 140 nm (method II). Hydroxychloroquine was measured at 266 nm, while ofloxacin was measured at 340 nm over the concentration range 4–40 ng/ml for hydroxychloroquine and 200–2000 ng/ml for ofloxacin with LOD of 0.467 and 25.3 ng/ml and LOQ of 1.42 and 76.6 ng/ml, respectively, for the two drugs. The two methods were validated following International Conference on Harmonization guidelines and were applied to the analysis of the two drugs in plasma with good percentage recoveries (109.73–93.17%).     

Molecular phylogenetic study of flavonoids in medicinal plants: a case study family Apiaceae

Journal of Plant Research - The current study examined the phylogenetic pattern of medicinal species of the family Apiaceae based on flavonoid groups production, as well as the overall mechanism of...     

RETRACTED ARTICLE: Acaricidal and pathogenic effects of the entomopathogenic fungus Beauveria bassiana on engorged females of the fowl tick,Argas persicus (Argasidae)

Experimental and Applied Acarology - This study examined the acaricidal, histopathological and genotoxic effects of the entomopathogenic fungus Beauveria bassiana on engorged females of the fowl...     

Effect of selenium and grape seed extract on indomethacin-induced gastric ulcers in rats

Indomethacin (IND) is a non-steroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the protective effect of selenium (SEL), grape seed extract (GSE), and both on IND-induced gastric mucosal ulcers in rats. Sprague–Dawley rats (200–250 g) were given SEL, GSE, and both by oral gavage for 28 days, and then gastric ulcers were induced by oral administration of 25 mg/kg IND. Malondialdehyde (MDA), non-enzymatic (reduced glutathione, GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants, prostaglandin E₂ (PGE₂) in gastric mucosa, and serum tumor necrosis factor alpha (TNF-α) were measured. Moreover, gastric ulcer index and preventive index were determined. Indomethacin increased the gastric ulcer index, MDA, TNF-α, and decreased PGE₂ and non-enzymatic (GSH) and enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) antioxidants. Pretreatment with SEL, GSE, and both significantly decreased the gastric ulcer index, MDA, and TNF and increased antioxidants and PGE₂. Histopathological observations confirm the gastric ulcer index and biochemical parameters. Selenium and GSE have a protective effect against IND-induced gastric ulcers through prevention of lipid peroxidation, increase of GSH, activation of radical scavenging enzymes, PGE₂ generation, and anti-inflammatory activity. Co-administration of GSE and SEL is more effective than GSE or SEL alone.     

Tobacco cigarette smoking exacerbates aortic calcification in an early stage of myocardial infarction in a female mouse model

Despite increased social awareness, marketing restraints, tobacco taxation, and available smoking cessation rehab programs, active and passive smoking remain a worldwide challenging epidemic and a key risk factor for cardiovascular diseases development. Although cardiovascular (CV) protection is more pronounced in women than in men due to estrogenic effects, tobacco cigarette smoking exposure seems to alter this protection by modulating estrogen actions via undefined mechanisms. Premenopausal cigarette smoking women are at higher risk of adverse CV effects than non-smokers. In this study, we investigated the impact of cigarette smoking on early CV injury after myocardial infarction (MI) in non-menopausal female mice. Aortic arch calcification, fibrosis, reactive oxygen species, and gene expression of inflammatory and calcification genes were exaggerated in mice exposed to cigarette smoke (CS). These findings suggest that aortic injury following MI, characterized by vascular smooth muscle cells transdifferentiation, calcification, inflammation, and collagen deposition but not cardiac dysfunction is exacerbated with CS exposure. The novel findings of this study highlight the importance of aortic injury on short and long-term prognosis in CS-exposed MI females. Linking those findings to estrogen alteration is probable and entails investigation.     

Relationship between virulence and aggressiveness in Plasmopara halstedii (sunflower downy mildew)

Relationship between virulence and aggressiveness was studied in seven Plasmopara halstedii (sunflower downy mildew) pathotypes including five progeny pathotypes of races 300, 304, 314, 704 and 714 arising from two parental pathotypes of races 100 and 710. Aggressiveness criteria including percentage infection, latent period, sporulation density and reduction of hypocotyl length were analysed in one sunflower inbred line showing a high level of quantitative resistance. There were significant differences between P. halstedii pathotypes for all aggressiveness criteria. Pathogenicity of progeny pathotypes as compared with parental ones (relationship between virulence and aggressiveness) seems to be positive, negative or uncorrelated. Hypothesis explaining these cases are discussed.     

Pathogenic groups identified among Plasmopara halstedii isolates belonging to several races

Pathogenic groups among 50 Plasmopara halstedii (sunflower downy mildew) isolates belonging to races 100, 300, 304, 314, 710, 704 and 714 were identified. Based on the reaction for the P. halstedii isolates to sunflower differential line D3, these isolates were divided into two groups as more virulent isolates of the 7xx races and the less virulent isolates of 100 and 3xx races. Index of aggressiveness (sporulation density/latent period) was calculated for each isolate and the presence of significant differences between isolates of 100 and 3xx races (more aggressive) and isolates of 7xx races (less aggressive) was revealed. Consequently, it seems that P. halstedii isolates may be divided into two pathogenic groups as more virulent and less aggressive isolates of 7xx races and less virulent and more aggressive isolates of the 100 and 3xx races.     

Acclimation of Plasmopara halstedii (sunflower downy mildew) in relationship with trade-off between virulence and aggressiveness in a local pathogen population

The acclimation in relationship with virulence cost was analysed for seven Plasmopara halstedii (sunflower downy mildew) isolates including five progeny isolates of several races descending from two parental isolates of races 100 and 710. Aggressiveness criteria were analysed in one sunflower inbred line showing a high level of quantitative resistance. Isolates of races 100 and 3xx were characterised with shorter latent period and higher sporulation density than isolates of races 7xx. All isolates showed high percentage infection values and caused a large reduction in seedling size except for one isolate involved in dwarfing. The seven isolates were divided, according to their virulence and aggressiveness, into two main groups as more aggressive isolates of the 100 and 3xx races which do not overcome the sunflower differential host D3, and less aggressive isolates of 7xx races which can overcome D3. Consequently, the 100 and 3xx avirulent races had a virulence cost measured by differences in aggressiveness (from 45.5 to 76.3%) compared to 7xx virulent races carrying unnecessary virulence gene.     

The Synechocystis PCC6803 MerA-Like Enzyme Operates in the Reduction of Both Mercury and Uranium under the Control of the Glutaredoxin 1 Enzyme

In a continuing effort to analyze the selectivity/redundancy of the three glutaredoxin (Grx) enzymes of the model cyanobacterium Synechocystis PCC6803, we have characterized an enzyme system that plays a crucial role in protection against two toxic metal pollutants, mercury and uranium. The present data show that Grx1 (Slr1562 in CyanoBase) selectively interacts with the presumptive mercuric reductase protein (Slr1849). This MerA enzyme plays a crucial role in cell defense against both mercuric and uranyl ions, in catalyzing their NADPH-driven reduction. Like MerA, Grx1 operates in cell protection against both mercury and uranium. The Grx1-MerA interaction requires cysteine 86 (C86) of Grx1 and C78 of MerA, which is critical for its reductase activity. MerA can be inhibited by glutathionylation and subsequently reactivated by Grx1, likely through deglutathionylation. The two Grx1 residues C31, which belongs to the redox active site (CX₂C), and C86, which operates in MerA interactions, are both required for reactivation of MerA. These novel findings emphasize the role of glutaredoxins in tolerance to metal stress as well as the evolutionary conservation of the glutathionylation process, so far described mostly for eukaryotes.