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71.
Md. Khalid Anwer Essam A. Ali Muzaffar Iqbal Mohammed Muqtader Ahmed Mohammed F. Aldawsari Ahmed Al Saqr Mohd Nazam Ansari M. Ali Aboudzadeh 《Molecules (Basel, Switzerland)》2022,27(1)
Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations. 相似文献
72.
An analysis of the effects induced by F, Cl, and Br-substituents at the α-position of both, the hydroxyl or the amino group for a series of amino-alcohols, HOCH2(CH2)nCH2NH2 (n = 0–5) on the strength and characteristics of their OH···N or NH···O intramolecular hydrogen bonds (IMHBs) was carried out through the use of high-level G4 ab initio calculations. For the parent unsubstituted amino-alcohols, it is found that the strength of the OH···N IMHB goes through a maximum for n = 2, as revealed by the use of appropriate isodesmic reactions, natural bond orbital (NBO) analysis and atoms in molecules (AIM), and non-covalent interaction (NCI) procedures. The corresponding infrared (IR) spectra also reflect the same trends. When the α-position to the hydroxyl group is substituted by halogen atoms, the OH···N IMHB significantly reinforces following the trend H < F < Cl < Br. Conversely, when the substitution takes place at the α-position with respect to the amino group, the result is a weakening of the OH···N IMHB. A totally different scenario is found when the amino-alcohols HOCH2(CH2)nCH2NH2 (n = 0–3) interact with BeF2. Although the presence of the beryllium derivative dramatically increases the strength of the IMHBs, the possibility for the beryllium atom to interact simultaneously with the O and the N atoms of the amino-alcohol leads to the global minimum of the potential energy surface, with the result that the IMHBs are replaced by two beryllium bonds. 相似文献
73.
Nada Abdullah Yahya Tamimi Sergey Dobretsov Najwa Al Balushi Jalila Alshekaili Hamed Al Balushi Mahmood Al Kindi Syed Imran Hassan Shadia Al Bahlani Benjamin K. Tsang Ikram A. Burney 《Molecules (Basel, Switzerland)》2021,26(12)
High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin. 相似文献
74.
Nilufar Z. Mamadalieva Fadia S. Youssef Hidayat Hussain Gokhan Zengin Adriano Mollica Nawal M. Al Musayeib Mohamed L. Ashour Bernhard Westermann Ludger A. Wessjohann 《Molecules (Basel, Switzerland)》2021,26(21)
The antioxidant and enzyme inhibitory potential of fifteen cycloartane-type triterpenes’ potentials were investigated using different assays. In the phosphomolybdenum method, cycloalpioside D (6) (4.05 mmol TEs/g) showed the highest activity. In 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) cation radical scavenging assays, cycloorbicoside A-7-monoacetate (2) (5.03 mg TE/g) and cycloorbicoside B (10) (10.60 mg TE/g) displayed the highest activities, respectively. Oleanolic acid (14) (51.45 mg TE/g) and 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 7-monoacetate (4) (13.25 mg TE/g) revealed the highest reducing power in cupric ion-reducing activity (CUPRAC) and ferric-reducing antioxidant power (FRAP) assays, respectively. In metal-chelating activity on ferrous ions, compound 2 displayed the highest activity estimated by 41.00 mg EDTAE/g (EDTA equivalents/g). The tested triterpenes showed promising AChE and BChE inhibitory potential with 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol 2′,3′,4′,7-tetraacetate (3), exhibiting the highest inhibitory activity as estimated from 5.64 and 5.19 mg GALAE/g (galantamine equivalent/g), respectively. Compound 2 displayed the most potent tyrosinase inhibitory activity (113.24 mg KAE/g (mg kojic acid equivalent/g)). Regarding α-amylase and α-glucosidase inhibition, 3-O-β-d-xylopyranoside-(23R,24S)-16β,23;16α,24-diepoxycycloart-25(26)-en-3β,7β-diol (5) (0.55 mmol ACAE/g) and compound 3 (25.18 mmol ACAE/g) exerted the highest activities, respectively. In silico studies focused on compounds 2, 6, and 7 as inhibitors of tyrosinase revealed that compound 2 displayed a good ranking score (−7.069 kcal/mole) and also that the ΔG free-binding energy was the highest among the three selected compounds. From the ADMET/TOPKAT prediction, it can be concluded that compounds 4 and 5 displayed the best pharmacokinetic and pharmacodynamic behavior, with considerable activity in most of the examined assays. 相似文献
75.
Extract of natural plants is one of the most important metallic corrosion inhibitors. They are readily available, nontoxic, environmentally friendly, biodegradable, highly efficient, and renewable. The present project focuses on the corrosion inhibition effects of Peganum Harmala leaf extract. The equivalent circuit with two time constants with film and charge transfer components gave the best fitting of impedance data. Extraction of active species by sonication proved to be an effective new method to extract the inhibitors. High percent inhibition efficacy IE% of 98% for 283.4 ppm solutions was attained using impedance spectroscopy EIS measurements. The values of charge transfer Rct increases while the double layer capacitance Cdl values decrease with increasing Harmal extract concentration. This indicates the formation of protective film. The polarization curves show that the Harmal extract acts as a cathodic-type inhibitor. It is found that the adsorption of Harmal molecules onto the steel surface followed Langmuir isotherm. Fourier-transform infrared spectroscopy FTIR was used to determine the electron-rich functional groups in Harmal extract, which contribute to corrosion inhibition effect. Scanning electron microscopy SEM measurement of a steel surface clearly proves the anticorrosion effect of Harmal leaves. 相似文献
76.
Noureddine Bencheikh Mohamed Bouhrim Loubna Kharchoufa Omkulthom Mohamed Al Kamaly Hamza Mechchate Imane Es-safi Ahmed Dahmani Sabir Ouahhoud Soufiane El Assri Bruno Eto Mohamed Bnouham Mohammed Choukri Mostafa Elachouri 《Molecules (Basel, Switzerland)》2021,26(16)
Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use. 相似文献
77.
78.
Zirconacycles 1, obtained from diethyl 1-alkynylphosphonates, insert either acyl chlorides or nitriles to provide, after acidic workup, (E)-3-oxo-1-alkenylphosphonates, 2, in isolated yields of 55-83%. Insertion produces only one regio- and stereoisomer. The reaction is quite general and proceeds well with both aliphatic and aromatic acyl chlorides. Acetonitrile and p-methoxybenzonitrile also inserted efficiently. Insertion of isobutyl chloroformate produced the vinylphosphonocarboxylate, 2c, the first representative of this class of compounds. 相似文献
79.
Ondřej Linhart Alžběta Kolorosová-Mrázová Jan Kratzer Jakub Hraníček Václav Červený 《Analytical letters》2019,52(4):613-632
An ultraviolet-photochemical generator (UV-PVG) capable of post-column on-line transformation of both organic and inorganic mercury species to cold vapor (Hg0) with subsequent detection by quartz tube-atomic absorption spectrometry (QT-AAS) was developed. Mercury(II), methylmercury(I), ethylmercury(I), and phenylmercury(I) were successfully detected after separation by reversed-phase high-performance liquid chromatography (RP-HPLC). Two types of AAS detectors were compared. The first was a commonly used line-source instrument while the second was a high-resolution continuum source (HR-CS) AAS. The latter provided better limits of detection: 0.47?µg?L?1 for Hg(II), 0.84?µg?L?1 for methylmercury(I), 0.80?µg?L?1 for ethylmercury(I), and 2.0?µg?L?1 for phenylmercury(I). The repeatability at 30?μg?L?1 was 3.6%, 4.1%, 6.2%, and 4.5% for these species (n?=?10). These figures of merit were comparable with those reported for more sensitive atomic fluorescence spectrometry. Nine sample extraction procedures were investigated. Extraction by tetramethylammonium hydroxide and HCl at 75?°C was selected as the only method compatible with the proposed separation and detection steps providing high extraction efficiency and no changes in mercury speciation. The applicability of the proposed high-performance liquid chromatography–ultraviolet-photochemical vapor generation–quartz tube-atomic absorption spectrometry method was demonstrated using fish samples and certified reference materials (CRM) DOLT-4 (dogfish liver) and ERM-CE464 (tuna fish). The results were comparable to those obtained by a reference method based on L-cysteine extraction and high-performance liquid chromatography–inductively coupled plasma-mass spectrometry (HPLC–ICP-MS) determination. 相似文献
80.
Ratan W. Jadhav Dr. Mohammad Al Kobaisi Dr. Lathe A. Jones Prof. Ajayan Vinu Prof. Sheshanath V. Bhosale 《ChemistryOpen》2019,8(9):1154-1166
Aminoglycosides, a class of antibiotics that includes gentamicin, kanamycin, neomycin, streptomycin, tobramycin and apramycin, are derived from various streptomyces species. Despite the significant increase in the antibacterial resistant pathogens, aminoglycosides remain an important class of antimicrobial drugs due to their unique chemical structure which offers a broad spectrum of activity. The modification of antibiotics and their subsequent use in supramolecular chemistry is rarely reported. Given the importance of aminoglycosides, here we give a brief overview on the modification of 4,5- and 4,6-disubstituted deoxystreptamine classes of aminoglycosides through supramolecular chemistry and their potential for real world applications. We also make the case that the work in this area is gaining momentum, and there are significant opportunities to meet the challenges of modern antibiotics through the modification of aminoglycosides by harnessing the advantages of supramolecular chemistry. 相似文献