Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acyclovir and acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drugs with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320nm or the fluorescence intensity of the produced cerous(III) ion at 361-363nm (excitation at 250nm). Beer's law obeyed from 2 to 8, 0.25 to 2.5microgcm-1 acyclovir, 1 to 7 and 0.25 to 2.5microgml-1 acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed method were successfully applied for determination of the selected drugs in their pharmaceutical preparations with good recoveries.     

Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics,In Vitro,and In Vivo Studies

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds (1–4) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC₅₀) and SARS-CoV-2 inhibitory concentrations (IC₅₀). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1, rutin 2, gallic acid 3, and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2, gallic acid 3, and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC₅₀ values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.     

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.     

Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes

The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7′,8,8′-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.     

Rp-HPLC Determination of Quercetin in a Novel D-α-Tocopherol Polyethylene Glycol 1000 Succinate Based SNEDDS Formulation: Pharmacokinetics in Rat Plasma

Despite its proven efficacy in diverse metabolic disorders, quercetin (QU) for clinical use is still limited because of its low bioavailability. D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) is approved as a safe pharmaceutical adjuvant with marked antioxidant and anti-inflammatory activities. In the current study, several QU-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were investigated to improve QU bioavailability. A reversed phase high performance liquid chromatography (RP-HPLC) method was developed, for the first time, as a simple and sensitive technique for pharmacokinetic studies of QU in the presence of TPGS SNEDDS formula in rat plasma. The analyses were performed on a Xterra C₁₈ column (4.6 × 100 mm, 5 µm) and UV detection at 280 nm. The analytes were separated by a gradient system of methanol and phosphate buffer of pH 3. The developed RP-HPLC method showed low limit of detection (LODs) of 7.65 and 22.09 ng/mL and LOQs of 23.19 and 66.96 ng/mL for QU and TPGS, respectively, which allowed their determination in real rat plasma samples. The method was linear over a wide range, (30–10,000) and (100–10,000) ng/mL for QU and TPGS, respectively. The selected SNEDDS formula, containing 50% w/w TPGS, 30% polyethylene glycol 200 (PEG 200), and 20% w/w pumpkin seed oil (PSO), showed a globule size of 320 nm and −28.6 mV zeta potential. Results of the pharmacokinetic studies showed 149.8% improvement in bioavailability of QU in SNEDDS relative to its suspension. The developed HPLC method proved to be simple and sensitive for QU and TPGS simultaneous determination in rat plasma after oral administration of the new SNEDDS formula.     

Granger-Causality Inference of the Existence of Unobserved Important Components in Network Analysis

Detecting causal interrelationships in multivariate systems, in terms of the Granger-causality concept, is of major interest for applications in many fields. Analyzing all the relevant components of a system is almost impossible, which contrasts with the concept of Granger causality. Not observing some components might, in turn, lead to misleading results, particularly if the missing components are the most influential and important in the system under investigation. In networks, the importance of a node depends on the number of nodes connected to this node. The degree of centrality is the most commonly used measure to identify important nodes in networks. There are two kinds of degree centrality, which are in-degree and out-degree. This manuscrpt is concerned with finding the highest out-degree among nodes to identify the most influential nodes. Inferring the existence of unobserved important components is critical in many multivariate interacting systems. The implications of such a situation are discussed in the Granger-causality framework. To this end, two of the most recent Granger-causality techniques, renormalized partial directed coherence and directed partial correlation, were employed. They were then compared in terms of their performance according to the extent to which they can infer the existence of unobserved important components. Sub-network analysis was conducted to aid these two techniques in inferring the existence of unobserved important components, which is evidenced in the results. By comparing the results of the two conducted techniques, it can be asserted that renormalized partial coherence outperforms directed partial correlation in the inference of existing unobserved important components that have not been included in the analysis. This measure of Granger causality and sub-network analysis emphasizes their ubiquitous successful applicability in such cases of the existence of hidden unobserved important components.     

Spectrophotometric stability-indicating methods for the determination of leflunomide in the presence of its degradates

Five simple and sensitive methods were developed for the determination of leflunomide (I) in the presence of its degradates 4-trifluoromethyl aniline (II) and 3-methyl-4-carboxy isoxazole (III). Method A was based on differential derivative spectrophotometry by measuring the delta(1)D value at 279.5 nm. Beer's law was obeyed in the concentration range of 2.00-20.00 microg/mL with mean percentage accuracy of 100.07 +/- 1.32. Method B depended on first-derivative spectrophotometry and measuring the amplitude at 253.4 nm. Beer's law was obeyed in the concentration range of 2.00-16.00 microg/mL with mean percentage accuracy of 98.42 +/- 1.61. Method C was based on the reaction of degradate (II) with 2,6-dichloroquinone-4-chloroimide (Gibbs reagent). The colored product was measured at 469 nm. Method D depended on the reaction of degradate (II) with para-dimethyl aminocinnamaldehyde (p-DAC). The absorbance of the colored product was measured at 533.4 nm. Method E utilized 3-methyl-2-benzothiazolinone hydrazone in the presence of cerric ammonium sulfate with degradate (II). The green colored product was measured at 605.5 nm. The linearity range was 40.00-280.00, 2.40-24.00, and 30-250 microg/mL with mean percentage accuracy of 100.75 +/- 1.21, 100.13 +/- 1.45, and 99.74 +/- 1.39 for Methods C-E, respectively. All variables were studied to optimize the reaction conditions. The proposed methods have been successfully applied to the analysis of leflunomide in pharmaceutical dosage forms and the results were statistically compared with that previously reported.     

Spectrophotometric and spectrofluorimetric methods for analysis of acyclovir and acebutolol hydrochloride

Simple and sensitive spectrophotometric and spectrofluorimetric methods are described for analysis of acebutolol hydrochloride. The proposed methods are based on oxidation of the selected drug with cerium(IV) ion in acidic medium with subsequent measurement of either the decrease in absorbance at 320 nm or the fluorescence intensity of the produced cerous(III) ion at 363 nm (excitation at 250 nm). Beer's law obeyed from 1.0-7.0 microg ml(-1) and 0.25-2.5 microg ml(-1) acebutolol hydrochloride, using the spectrophotometric and spectrofluorimetric method, respectively. The proposed methods were successfully applied for determination of the selected drug in its pharmaceutical preparation with good recoveries.