32 research outputs found
An Advanced Machine Learning Based Energy Management of Renewable Microgrids Considering Hybrid Electric Vehiclesâ Charging Demand
Renewable microgrids are new solutions for enhanced security, improved reliability and boosted power quality and operation in power systems. By deploying different sources of renewables such as solar panels and wind units, renewable microgrids can enhance reducing the greenhouse gasses and improve the efficiency. This paper proposes a machine learning based approach for energy management in renewable microgrids considering a reconfigurable structure based on remote switching of tie and sectionalizing. The suggested method considers the advanced support vector machine for modeling and estimating the charging demand of hybrid electric vehicles (HEVs). In order to mitigate the charging effects of HEVs on the system, two different scenarios are deployed; one coordinated and the other one intelligent charging. Due to the complex structure of the problem formulation, a new modified optimization method based on dragonfly is suggested. Moreover, a self-adaptive modification is suggested, which helps the solutions pick the modification method that best fits their situation. Simulation results on an IEEE microgrid test system show its appropriate and efficient quality in both scenarios. According to the prediction results for the total charging demand of the HEVs, the mean absolute percentage error is 0.978, which is very low. Moreover, the results show a 2.5% reduction in the total operation cost of the microgrid in the intelligent charging compared to the coordinated scheme
Metabolomic profile, anti-trypanosomal potential and molecular docking studies of <i>Thunbergia grandifolia</i>
Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90âÎŒg/mL within 72âh. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves
Synthesis and Biological Evaluation of Some New Thiazolodiazepine Analogues as CNS Active Agents
PhDThe ultraâshort ac ng ac vity of ethyl 8âoxoâ5,6,7,8âtetrahydroâthiazolo[3,2âa]
[1,3]diazepinâ3âcarboxylate (HIEâ124, 12), as a member of a novel class, which might overcome
many of the disadvantages and problems that usually associated the use of thiopental or
benzodiazepines as intravenous anesthetic agents has been reported.
The present investigation is directed toward the synthesis of new derivatives of the
parent thiazolo[3,2âa][1,3]diazepine (HIEâ124, 12), in continuation to the previous patented
efforts in this area. These derivatives possess the potential to exhibit a promising and varying
range of CNS activities, including, among others, hypnotic and anticonvulsant activities.
The proposed compounds were synthesized according to the designed strategy.
Structure elucidation of the synthesized intermediates and final products was attained by the
aid of IR, 1H, 13C NMR, and mass spectrometry. The synthesized compounds were evaluated for
various CNS activities.
The new analogues Ethyl 3âmethylâ8âoxoâ5,6,7,8âtetrahydroâthiazolo[3,2âa]
[1,3]diazepineâ2âcarboxylate (35) and 2âBromoâ3âmethylâ6,7âdihydroâthiazolo[3,2âa]
[1,3]diazepinâ8(5H)âone (40) showed marginal hypnotic potency compared to what was
reported about the parent compound HIEâ124 (12).
Biological screening results allowed the allocation of two potent anticonvulsant agents
worth patency. Compounds 35 and 40 proved to be the most active compounds in the present
inves ga on as an convulsants with remarkable 100% protec on against PTZ induced
convulsions as compared with the standard drug valproic acid. It is worth mentioning that
compounds 35 (0.78 mmole/kg) and 40 (0.39 mmole/kg) proved to be almost two and four fold
more ac ve, respec vely; than the used posi ve control sodium valproate (1.38 mmole/kg).
Structure activity correlation of the obtained results revealed that, CNS activity is
embedded in the structure core (8âoxoâ5,6,7,8âtetrahydroâthiazolo[3,2âa][1,3]diazepine) of the
investigated compounds. Structure activity relationships (SAR) were deduced from the obtained
data.
These studied 8âoxoâ5,6,7,8âtetrahydroâthiazolo[3,2âa][1,3]diazepine analogues could be
considered as useful templates for future development and further derivatization or
modification to obtain more potent CNS active compounds
Synthesis, Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents
In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14aân, 16aâd, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 ÎŒg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones
Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation
Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a–f and 9a–h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%–58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs
Simultaneous Quantification of a Neoadjuvant Treatment Used in Locally Advanced Breast Cancer Using an Eco-Friendly UPLC-MS/MS Method: A Pharmacokinetic Study in Rat Plasma
Recently, neoadjuvant treatment has turned out to be a feasible alternative for individuals suffering from locally advanced breast cancer. The neoadjuvant therapy is a type of chemotherapy that is given either before or after surgeries to diminish a tumor and minimize the likelihood of recurrence. This article demonstrates the development of a unique bioanalytical validated sensitive method by means of an ultra high performance liquid chromatographyâtandem mass spectrometry (UPLCâMS/MS) approach for the concurrent estimation of neoadjuvant treatments including 5-Fluorouracil, Doxorubicin, and Capecitabine in rat plasma. Samples were prepared using the fine minor QuEChERS process and analyzed using a Shimadzu-C18 column via an isocratic separation. Acetonitrile:water in the ratio of (30:70) (both containing 0.1 percent formic acid v/v) was the mobile phase employed at a flow rate of 0.20 mL/min. At concentrations of 50.00â500.00 ng/mL for 5-Fluorouracil, 25.00â500.00 ng/mL for Doxorubicin, and 5.00â100.00 ng/mL for Capecitabine, the procedure was shown to be linear. The limit of detection (LOD) was assessed in ng/mL and varied from 1.33 to 13.50. Relative standard deviations for precision were below 2.47 percent over the whole concentration range. For all analytes, the average recovery rate varied from 73.79 to 116.98 percent. A preliminary pharmacokinetic study was successfully performed in real rats to evaluate the procedure efficiency
Multistaged In Silico Discovery of the Best SARS-CoV-2 Main Protease Inhibitors amongst 3009 Clinical and FDA-Approved Compounds
As a follow-up to our teamworkâs former work against SARS-CoV-2, eight compounds (ramelteon (68), prilocaine (224), nefiracetam (339), cyclandelate (911), mepivacaine (2325), ropivacaine (2351), tasimelteon (2384), and levobupivacaine (2840)) were revealed as the best potentially active SARS-CoV-2 inhibitors targeting the main protease (PDB ID: 5R84), Mpro. The compounds were named in the midst of 3009 FDA and clinically approved compounds employing a multistaged in silico method. A molecular fingerprints study with GWS, the cocrystallized ligand of the Mpro, indicated the resemblance of 150 candidates. Consequently, a structure similarity experiment disclosed the best twenty-nine analogous. Then, molecular docking studies were done against the Mpro active site and showed the binding of the best compounds. Next, a 3D-pharmacophore study confirmed the obtained results for the eight compounds by exhibiting relative fit values of more than 90% (except for 68, 74%, and 2384, 83%). Levobupivacaine (2840) showed the most accurate docking and pharmacophore scores and was picked for further MD simulations experiments (RMSD, RMSF, Rg, SASA, and H-H bonding) over 100âns. The MD simulations results revealed the accurate binding as well as the optimum dynamics of the Mpro-levobupivacaine complex. Finally, MM-PBSA studies were conducted and indicated the favorable bonding of the Mpro-levobupivacaine complex with a free energy value of â235âkJ/mol. The fulfilled outcomes hold out hope of beating COVID-19 through more in vitro and in vivo research for the named compounds
GC/MS Analysis of Essential Oil and Enzyme Inhibitory Activities of Syzygium cumini (Pamposia) Grown in Egypt: Chemical Characterization and Molecular Docking Studies
Syzygium cumini (Pomposia) is a well-known aromatic plant belonging to the family Myrtaceae, and has been reported for its various traditional and pharmacological potentials, such as its antioxidant, antimicrobial, anti-inflammatory, and antidiarrheal properties. The chemical composition of the leaf essential oil via gas chromatographyâmass spectrometry (GC/MS) analysis revealed the identification of fifty-three compounds representing about 91.22% of the total oil. The identified oil was predominated by α-pinene (21.09%), followed by ÎČ-(E)-ocimene (11.80%), D-limonene (8.08%), ÎČ-pinene (7.33%), and α-terpineol (5.38%). The tested oil revealed a moderate cytotoxic effect against human liver cancer cells (HepG2) with an IC50 value of 38.15 ± 2.09 ”g/mL. In addition, it effectively inhibited acetylcholinesterase with an IC50 value of 32.9 ± 2.1 ”g/mL. Furthermore, it showed inhibitory properties against α-amylase and α-glucosidase with IC50 values of 57.80 ± 3.30 and 274.03 ± 12.37 ”g/mL, respectively. The molecular docking studies revealed that (E)-ÎČ-caryophyllene, one of the major compounds, achieved the best docking scores of â6.75, â5.61, and â7.75 for acetylcholinesterase, α-amylase, and α-glucosidase, respectively. Thus, it is concluded that S. cumini oil should be considered as a food supplement for the elderly to enhance memory performance and for diabetic patients to control blood glucose
The Antioxidant and Enzyme Inhibitory Potential of <i>n</i>-Hexane-Extracted Oils Obtained from Three Egyptian Cultivars of the Golden Dewdrop <i>Duranta erecta</i> Linn. Supported by Their GC-MS Metabolome Analysis and Docking Studies
Duranta erecta Linn. has a longstanding history for use in folk remedy for several disorders. Its hydroalcoholic extract has been investigated intensely in the treatment of many ailments, but to date very few data are presented to explain the pharmacological use of its oil. In this study, the chemical profiles of the leaf oils extracted from three Egyptian Duranta erecta cultivars, namely âGreenâ, âGolden edgeâ, and âVariegataâ are traced using GC-MS analysis. D. erecta âGreenâ showed predominance of vitamin E (22.7%) and thunbergol (15%) whereas D. erecta âGolden edgeâ and âVariegataâ contained tetratetracontane as a major component in their oils. The highest phenolic and flavonoid contents, displayed as gallic acid and rutin equivalents per gram oil, respectively, were observed in the âGolden edgeâ and âVariegataâ cultivars, which was reflected by their strong DPPH and ABTS scavenging activities as well as the highest reducing power in both CUPRAC and FRAP assays. D. erecta âGreenâ displayed better metal chelating potential, which may be attributed to its content of vitamin E. All cultivars showed similar enzyme inhibitory profiles. The best inhibition of α-glucosidase and α-amylase was observed by D. erecta âGreenâ. In silico studies of the major constituents docked on the active sites of the target enzymes NADPH oxidase, amylase, glucosidase, butyrylcholinesterase, and tyrosinase revealed high binding scores, which justified the biological activities of the tested oils
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Novel 3-(6-methylpyridin-2-yl)coumarin-based chalcones as selective inhibitors of cancer-related carbonic anhydrases IX and XII endowed with anti-proliferative activity.
Carbonic anhydrases (CAs) are one of the promising targets for the development of anticancer agents. CA isoforms are implicated in various physiological processes and are expressed in both normal and cancerous cells. Thus, non-isoform selective inhibitors are associated with several side effects. Consequently, designing selective inhibitors towards cancer-related hCA IX/XII rather than the ubiquitous cytosolic isozymes hCA I and II is the main research objective in the field. Herein, a new series of 3-(6-methylpyridin-2-yl)coumarin derivatives 3 and 5a-o was designed and synthesised. The CA inhibition activities for the synthesised coumarins were analysed on isoforms hCA I, II, IX, and XII. Interestingly, both cancer-linked isoforms hCA IX/XII were inhibited by the prepared coumarins with inhibition constants ranging from sub- to low-micromolar range, whereas hCA I and II isoforms haven't been inhibited up to 100â”M. Furthermore, the target coumarins were assessed for their antitumor activity on NCI-59 human cancer types