Pharmaceutical Chemistry Journal最新文献

Isosteviol has been investigated with a cardio-treating effect on cardiomyocyte hypertrophy. However, its hydrophilicity suppressed its efficient cellular uptake for targeting the heart. Exosomes were seen as delivery vesicles with excellent histocompatibility; thus, an isosteviol-loaded exosome (Istv-exo) was prepared for cardiopulmonary delivery in this study. For in vivo evaluation, the Istv-exo and isosteviol saline solution was used for inhalation or intragastric administration on Sprague–Dawley rats for an assay of dynamic distribution. The higher biodistribution of Istv-exo in the lung and heart has been confirmed by the dynamic content curve. Istv-exo/isosteviol solution was administered by inhalation/intragastrically to Myh6^-/- mice, a cardiomyocyte hypertrophy model, to explore the therapeutic effect. The heart function of the mice was measured using echocardiography and in situ imaging was used to analyze the morphology of the heart. The higher level of left ventricular internal dimension, ejection fraction, and cardiac output in echocardiography indicated that Istv-exo enhanced improvement of myocardial function. The attenuation of cardiomyocyte hypertrophy in mice treated with inhalation of Istv-exo determined that it contributed to the reversal of pathological hypertrophy phenotypes. Wheat germ agglutinin staining confirmed that cardiomyocyte hypertrophy was reversed to varying degrees in the Istv-exo, intragastrical isosteviol, and positive control groups. Hematoxylin and eosin staining exhibited the enlarging left ventricular and thinning ventricular wall of the treated mice. Drastically less collagen fiber was observed in the positive control group and Istv-exo group. The inhalation administration of isosteviol-loaded exosomes may be better in therapy for cardiomyocyte hypertrophy than intragastric usage of isosteviol.

There is good evidence that fatty acid derivatives have antibacterial activity and represent a promising approach to developing the next generation of antibacterial agents. In the present work, some new isoquinolin derivatives were synthesized via the Betti reaction. Three-component reaction of aryl aldehydes, 2,7-naphthalenediol and ammonium carboxylate of fatty acids with different chains in EtOH under reflux conditions offered related isoquinolin compounds in good to excellent yields. Some advantages of this procedure are short reaction times, free catalyst, high yield of products and easy work-up. The structure of synthesized compounds was characterized by IR, ¹H, and ¹³C NMR data as well as microanalysis results. In addition, these novel materials were evaluated for their biological activities against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) bacteria. The obtained data confirm that isoquinolin derivatives 4c, 4e, 4f, 4g, 4m, 4n, 4p, 4q exert excellent antimicrobial activity against these tested bacterial strains.

Raspberry ketone (RK) is an active constituent obtained from Rubus idaeus (Rosaceae), which has been traditionally used against diabetes, hypertension, etc. The objective of this study was to assess the cardioprotective effect of RK against isoproterenol (ISO)-induced cardiac hypertrophy in Wistar rats. Rats were arbitrarily divided into six groups and were treated daily with raspberry ketone (100 and 200 mg/kg), fenofibrate (80 mg/kg) and propranolol (10 mg/kg) along with ISO (3 mg/kg, subcutaneously) for 28 days. Twenty-four hours after the last dose administration, serum and heart tissue samples from the animals were taken and their hemodynamic (blood pressure, heart rate], biochemical (CK-MB, LDH, troponin-T, PPAR-α, apolipoprotein C III, c-reactive protein, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, malondialdehyde, reduced glutathione, superoxide dismutase, catalase, Na⁺-K⁺-ATPase, total antioxidant capacity, and nitric oxide), histopathological, and immunohistochemical (caspase-3, nuclear factor-κB, tumor necrosis factor-α) analysis was performed along with gravimetric analysis. Administration of ISO significantly altered the cardiac integrity and physiology and these changes were significantly averted by the administration of RK (100 and 200 mg/kg). These results were also found to be comparable with those of the standard drugs, fenofibrate and propranolol. The assessment of cardiac morphology by histopathological and immunohistochemical analysis further validated these results. This study thus demonstrated that RK at doses of 100 and 200 mg/kg showed a dose-dependent decrease in inflammation, oxidative stress, and dyslipidemia against ISO-induced cardiac hypertrophy in Wistar rats, which could be due to agonistic action of RK at PPAR-α receptor subtype.

The effect of thioctic acid (TA), 2-ethyl-6-methyl-3-hydroxypyridine hydrochloride (emoxypine), and their ester derivative (2-ethyl-6-methylpyridinol-3-yl-thiooctanoate, thioxypine) on the behavior of rats in an elevated plus maze (EPM) was studied. Intraperitoneal administration (three times) of TA, emoxypine, and their equimolar mixture in single doses of 36.25, 72.5, and 145 μmol/kg enhanced individual manifestations of anxious behavior in the EPM but did not cause full-blown anxiogenic effects. Similar pro-anxiogenic effects were observed when TA was administered in a dose of 36.25 μmol/kg and emoxypine in doses of 72.5 and 145 μmol/kg. The equimolar mixture of the non-esterified components of thioxypine had a pro-anxiogenic effect in doses of 36.25 and 72.5 μmol/kg. Combination of TA and 2-ethyl-6-methyl-3-hydroxypyridine into the ester potentiated their pro-anxiogenic activity, which manifested as an extensive anxiogenic effect of thioxypine when administered three times in a dose of 145 μmol/kg.

The transdermal route is considered one of the most favourable routes of drug delivery over other conventional routes. The stratum corneum (SC) is the main barrier to the delivery of drugs by the transdermal route. Many strategies are employed to overcome SC barrier properties like lipid vesicles, permeation enhancers, physical methods, etc. The main objective of this research article was to explore and compare a few chemical penetration enhancers in combination with physical means like tape stripping and microneedle to enhance the transdermal permeation of caffeine. The transdermal gel of caffeine was prepared by dissolving the drug in distilled water containing various concentrations of chemical penetration enhancers, including Arlasolve DMI, ethanol, transcutol P and DMSO. Ex-vivo skin permeation and skin deposition studies were conducted on the transdermal gel alone and in combination with the microneedle or tape-stripping methods. The HPLC method analyzed the total amount of caffeine that permeated through the skin sample. The formulations containing Arlasolve DMI as a penetration enhancer showed the maximum drug penetration among all the penetration enhancers. A combination of microneedles with Arlasolve DMI showed the best skin permeation among all the methods tested. It was clear from the results that Arlasolve DMI would be a better option to use as a penetration enhancer in the dermatological formulations of caffeine in combination with a microneedle-based permeation enhancement method.

The new conjugate compound pyrrolylcarnosine was synthesized from the natural antioxidant carnosine and the aromatic five-membered nitrogen heterocycle pyrrole. The synthesis of pyrrolylcarnosine was described. Its physicochemical properties and biological activity in various oxidative stress models were evaluated. The results showed that pyrrolylcarnosine was characterized by resistance to hydrolysis by serum carnosinase and exhibited high antioxidant activity in model experiments. It had a neuroprotective effect under oxidative stress induced by the neurotoxin AAPH, increasing the viability of a differentiated culture of human neuroblastoma SH-SY5Y and protecting it from death. In general, the results indicated creation of a new drug based on pyrrolylcarnosine was promising.

In the area of drug development the solubility of an active ingredient plays a very crucial and vital part and is of the highest significance. Increasing importance is being placed on the research into active ingredient solubilization. The designing of a host guest complex with a compound that has a higher dissolubility profile can work with the solubilization of lipophilic drugs. In this research work optimized nano-carriers were effectively synthesized utilizing thin-film hydration strategies. The drug sulfonated calix[4]resorcinarene blend (1:10) containing ethanol was dispersed and sonicated with an estimated three cycles, at an amplitude 70 with a 20-s interval for an optimized time. The synthesized nanovesicles have an average diameter of 477.7 nm, a higher mono dispersity (PDI-0.282), and a greater loading capacity of the drugs is 95%. Atomic force microscopy in accordance with dynamic light-scattering spectra confirmed the spherical shape of paclitaxel-loaded sulfonated calix[4]resorcinarene nanovesicles. In vitro release of medication from nanovesicles affirmed the extended discharge pattern of drugs with r² of 0.9902 compared with the commercial formulation available on the market. MTT assay is performed to access the toxicity of the sufonated calix[4]resorcinarene in vitro. IC₅₀ values indicate that synthesized sufonated calix[4]resorcinarene shows better IC₅₀ values than paclitaxel and taxol. The formulated nanovesicles from sulfonated calix[4]resorcinarene showed an ideal size with higher capacity for binding drug and provide better patient compliance, which are positive for their expected application as a modular drug delivery platform for anti-cancer drugs.

The purpose of the present research was to study peculiarities in the accumulation of natural and artificial radioisotopes in medicinal plant raw material using nettle (Urtica dioica L.) leaves as an example. The specific activities of the main long-lived artificial radioisotopes (cesium-137 and strontium-90) and naturally occurring radionuclides (thorium-232, potassium-40, and radium-226) in experimental samples of upper soil layers and nettle leaves were determined on a RADEK MKGB-01 spectrometer-radiometer. All studied samples of nettle leaves collected in natural and artificial phytocenoses of Voronezh Region met existing radiation safety requirements (first group). A correlation analysis of the specific activities of artificial and natural radionuclides in the soil and nettle leaves showed a close relationship between these numerical indicators that confirmed their contamination primarily through soil. The specific activities of strontium-90, cesium-137, thorium-232, potassium-40, and radium-226 in the medicinal plant raw material increased as their specific activities in the soil increased. High accumulations of cesium-137 and potassium-40 from the upper soil layers were noted for nettle leaves growing in Voronezh Region. A detailed analysis of the dependence of the calculated accumulation coefficients of natural and artificial radioisotopes in nettle leaves revealed trends toward their decrease with increases in the specific activities of the radionuclides in the soil, which indicated physical mechanisms for regulating their uptake into the plant were present.