Cytotoxic activity of Thymus capitatus collected from Hail region in Saudi Arabia with mechanistic study via induction of caspase-dependent apoptosis and S-phase arrest

Thymus capitatus is a plant grows in Mediterranean area and some Arab countries such as Saudi Arabia. It possesses numerous medicinal values. Its common name is Zaatar and it belongs to family Lamiaceae Thymus capitatus leaves and stem were collected from Hail region, Saudi Arabia. Then both leaves and stem were extracted with ethanol. This study was performed to evaluate cytotoxic activity of Thymus capitatus leaves and stem ethanolic extract in details. Doxorubicin was used as a standard and the relevant half maximal inhibitory concentration (IC50) values were computed for each cell line by 3-(4,5- diemthylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, further mechanistic study was carried out by using Apoptosis assay to explore cytotoxic activity of plant extract. Both leaves and stems extracts were screened against HepG2, A-549, HCT-116 and   MCF-7 cancer cell lines. It was found that leaves’ extract shows high and moderate cytotoxic activity against both A-549 and HepG2 cancer cell lines, respectively (with IC50 = 13.6 and 21.5 μg/ml, respectively), while stem’s extract exerted moderate cytotoxic activity against A-549 cancer cell lines (with IC50 = 21.38 μg/ml).  Further mechanistic study was carried out on A-549 cells by using apoptosis assay. It showed that leaves’ extract resulted in arrest of S-phase and caused apoptosis through activation of caspase-3, p53 and Bax, in addition to down regulation of Bcl-2

Antioxidant and cytotoxic activities of Artemisia monosperma L. and Tamarix aphylla L. essential oils

Essential (volatile) oil from leaves of Artemisia monosperma L. belonging to family Asteraceae, and aerial parts of Tamarix aphylla L. (Athel) belonging to family Tamaricaceae were collected from the desert of Ha'il region, northern region of Saudi Arabia, hydro distilled by Clevenger apparatus and analysed by means of GC-MS techniques. Antioxidant activities of essential oils of A. monosperma and T. aphylla compared with ascorbic acid and butylated hydroxytoluene (BHT) as reference antioxidant compound were determined by method of DPPH radical scavenging assay and ABTS assay. In vitro screening of potential cytotoxicity of essential oils was also evaluated against human promyelocytic leukaemia cell lines (HL60 and NB4). The GC/MS analysis of A. monosperma essential oil resulted in identification of 61 components predominated mainly by β-Pinene as principal component (29.87%) and T. aphylla resulted in identification of 37 components of essential oil predominated mainly by 6,10,14- trimethyl-2-pentadecanone (21.43%) as principal component. Antioxidant activity as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and 2,2 -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) increased with increasing essential oil concentrations of A. monosperma and T. aphylla (25, 50, 75, 100 and 200 μg mL-1). The most pronounced increases detected in the high concentrations of the two essential oils. Biologically, essential oil extracts exhibited cytotoxicity effects in dose dependent manner against human promyelocytic leukaemia cell lines (HL60 and NB4). In conclusion, A. monosperma and T. aphylla essential oils could be valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles

Design, synthesis and cytotoxic evaluation of 2-amino-4- aryl-6-substituted pyridine-3,5-dicarbonitrile derivatives

Purpose: To synthesize novel pyridine derivatives and evaluate their efficiency as potent inhibitors of cyclin dependent kinase 2 (CDK2) enzyme for cancer therapy.Methods: Pyridine scaffold were synthesized using one-pot multicomponent condensation reaction of arylidine with different primary amines. The cytotoxic potential of the new compounds was assessed using various cell lines. Furthermore, molecular docking studies based on the crystal structure of CDK2 was carried out to determine the possible binding modes that influence the anticancer activities.Results: The results indicate that one-pot multicomponent reaction generated a series of functionalized pyridines with good yield. In vitro cytotoxicity study revealed superior cytotoxicity of the designed compounds against prostate and cervical cancer cell lines compared to 5-fluorouracil (standard anticancer compound) with half-maximal inhibitory concentration (IC50) values of 0.1 – 0.85 and 1.2 –74.1 μM, respectively. Finally, molecular modeling simulation of the newly synthesized compounds showed that they fit well and are stabilized into CDK2 active site via hydrogen bonding and hydrophobic interactions.Conclusion: The results indicate that the newly synthesized pyridine can exert potent anticancer activity presumably via inhibition of CDK2. However, this will need to be confirmed in in vivo studies

Cytotoxic activity of Thymus capitatus collected from Hail region in Saudi Arabia with mechanistic study via induction of caspase-dependent apoptosis and S-phase arrest

Thymus capitatus is a plant grows in Mediterranean area and some Arab countries such as Saudi Arabia. It possesses numerous medicinal values. Its common name is Zaatar and it belongs to family Lamiaceae Thymus capitatus leaves and stem were collected from Hail region, Saudi Arabia. Then both leaves and stem were extracted with ethanol. This study was performed to evaluate cytotoxic activity of Thymus capitatus leaves and stem ethanolic extract in details. Doxorubicin was used as a standard and the relevant half maximal inhibitory concentration (IC50) values were computed for each cell line by 3-(4,5- diemthylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. In addition, further mechanistic study was carried out by using Apoptosis assay to explore cytotoxic activity of plant extract. Both leaves and stems extracts were screened against HepG2, A-549, HCT-116 and   MCF-7 cancer cell lines. It was found that leaves’ extract shows high and moderate cytotoxic activity against both A-549 and HepG2 cancer cell lines, respectively (with IC50 = 13.6 and 21.5 μg/ml, respectively), while stem’s extract exerted moderate cytotoxic activity against A-549 cancer cell lines (with IC50 = 21.38 μg/ml).  Further mechanistic study was carried out on A-549 cells by using apoptosis assay. It showed that leaves’ extract resulted in arrest of S-phase and caused apoptosis through activation of caspase-3, p53 and Bax, in addition to down regulation of Bcl-2

Insight into possible therapeutic applications of Ephedra transitoria: in-vitro biological, toxicological activities and GC-MS analysis of aerial parts’ extract

Most Arab nations have arid regions where Ephedra transitoria, a plant, flourishes. It has a variety of medical benefits. It belongs to the Ephedraceae family. The plant's aerial portions were procured from the Hail region of Saudi Arabia, methanol was used to extract bioactive phytochemicals with variable solubility in an efficient manner, and the resulting extract was tested on several cancer cell lines. The extract's cytotoxic potential was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay method against standard vinblastine sulfate and for each cell line, the pertinent half maximal inhibitory concentration values were calculated. Additional apoptosis assays were conducted. Also, the antioxidant activity of plant extract was examined using 2, 2-Diphenyl-1-picrylhydrazyl and [2, 2’-azinobis-(3-ethylbenzothiazoline-6-sulfonate)] methods compared to ascorbic acid standard. Also, antimicrobial effect of extract was evaluated on different gram positive and gram-negative bacteria by zone inhibition and minimum inhibitory concentration assay methods. GC-MS analysis was further applied to identify major bioactive substances. Extract showed good cytotoxic activity against both lung and liver cancer cells with relevant half maximal inhibitory concentration values comparable to those of standard. Extract resulted in S-phase arrest, primarily via inducing apoptosis mediated through activating caspase-3, Bax, and p53 proteins. Plant extract showed good antibacterial activities against S. aureus, E. coli and B. subtilis. Also, it showed high antioxidant activity with relevant half maximal inhibitory concentration values comparable to those of standard. Some bioactive compounds were separated and identified by GC-MS analysis such as; ephedrine and quercetin. ephedra transitoria extract possess high cytotoxic activity against lung and liver cancer cells via S-phase arrest mediated by activation of apoptotic proteins. It also possesses high antioxidant and antibacterial activities

Application of Ion Selective Electrode for Determination of Lamivudine in Pure Form, Drug Product, Plasma and in presence of its Related Impurities Analytical & Bioanalytical Electrochemistry

Abstract-The field of Electro-chemical sensors development is now highly grown for the determination of traces amounts of drugs. A novel polyvinylchloride membrane sensor for the determination of lamivudine is prepared and characterized. The sensor is based on the use of the ion association complex of lamivudine anion with iron(II)-phenanthroline counter cation as an ion exchange site in the polyvinylchloride matrix. The performance characteristics of this sensor was evaluated according to IUPAC recommendations, which reveal a fast, stable and linear response for lamivudine over the concentration range of 10 -6 to 10 -2 mol L -1 for the sensor with anionic slope of 27.3 mV per concentration decade for the sensor. The direct potentiometric determination of lamivudine using the proposed sensor gave recovery of 99.57±0.62% for the sensor. The proposed sensor displayed useful analytical characteristics for the determination of lamivudine in bulk powder, pharmaceutical formulations, and biological fluids (plasma) and in the presence of some related impurities, namely cytosine, uracil and salicylic acid. Validation of the method shows suitability of the proposed sensor for the use in quality control assessment of lamivudine. The developed method was found to be simple, accurate and precise when compared with an official high performance liquid chromatographic method. Also the method allows direct determination of lamivudine without pretreatment or separation steps in turbid or colored solutions in presence of some related impurities

Development and validation of two chromatographic methods for the simultaneous determination of raubasine and almitrine besmesylate in pharmaceutical dosage form

A binary mixture of almitrine besmesylate (A) and raubasine (R) was determined by two different chromatographic methods. The first method was based on HPTLC separation of the two drugs followed by densitometric measurement of their spots at 245 and 285 nm for A and R, respectively. The separation was carried out using HPTLC silica gel F254 nanoplates with methanol:ammonia (10:8, v/v) as developing solvent. The linearity was achieved over concentration range of 0.5–8 μg/spot and 0.5–10 μg/spot with mean accuracy 100.79 ± 1.58 and 100.68 ± 1.78, for A and R, respectively. The second method involved the determination of A and R using reversed phase high performance liquid chromatography (HPLC) on C18 column using acetonitrile:potassium dihydrogen orthophosphate buffer pH = 4.7 (70:30, v/v) as mobile phase with flow rate at 2 ml/min. Quantitation was achieved using UV detection at 220 nm. A linear relationship was obtained over a concentration range of 0.75–105 μg ml−1 for both drugs with mean accuracy 100.85 ± 1.74 and 98.82 ± 1.31, for A and R, respectively. The methods were successfully applied for the determination of the cited drugs in dosage forms. The proposed methods were validated according to USP and were found to be valid and suitable for the assay of the cited drugs in dosage forms in quality control laboratories

Grid-Connected Solar PV Power Plants Optimization: A Review

Due to photovoltaic (PV) technology advantages as a clean, secure, and pollution-free energy source, PV power plants installation have shown an essential role in the energy sector. Nevertheless, the PV power plant cost of energy must be competitive when compared to traditional energy sources. Therefore, numerous studies are continuously being conducted aiming to optimize PV power plants, including components arrangements within the installation site, the inverter topology, cables, PV modules and inverters numbers, PV module tilt angle and shading effect. For selecting the most suitable combinations for system parameters, this study seeks to systematically analyze and synthesize the design of the PV power plant optimization from the current literature. The study also examines component sizing for PV power plants, involving PV modules tilt angle, inverter, transformer, and cables. Moreover, it provides an overview of the main components employed to install the PV power plant, which includes PV modules, inverter, transformer and wiring. It examines the different inverter topologies used in PV power plants along with a comparison between these topologies

Assessment of Newly Synthesized Triazole Compounds Using ZnO(NPs) as Antimicrobial Agents and Theoretical Studies for Inhibiting COVID-19

An efficient method using ZnO(NPs) was used to synthesize derivatives of s-substituted-1,2,4-triazoles with excellent yield. The structure of all newly formed triazoles was approved using the data extracted from their spectral and elemental analyses. Fifteen s-substituted-triazole derivatives were tested for their antimicrobial activity and the results indicated that triazole derivative 15 recorded the highest antimicrobial activity against Trichophyton mentagrophyte followed by Staphylococcus aureus and Bacillus cereus with clear zone diameters of 30, 28, and 15 mm when compared with the traditional antibiotics, with minimal lethal concentrations of 16, 32, and 64 µg/ml, respectively. While compounds 13c, 13b, 13a and 8a exhibited considerable antimicrobial activity against Gram-positive pathogens including B. cereus, S. aureus. The docking study for the most potent derivatives 8a, 13a, 13b, 13c and 15 against methicillin acyl-Penicillin binding protein 2a from methicillin-resistant S. aureus strain 27r at 2.60 A resolution (PDB: 1MWU) showed strong fit in the active site the methicillin acyl-Penicillin binding protein, especially for derivative 15. Due to the horror caused by the Corona pandemic during the past two years, we docked the s-substituted-1,2,4-triazole derivatives into the active site of SARS-CoV-2 main protease (6LU7). The docking result showed well-fitting and proper orientation of all triazole derivatives except the starting derivative 5. The physicochemical properties, pharmacokinetics, and drug-likeness of the most active s-substituted-1,2,4-triazole derivatives were studied using SwissADME. The results of computational studies and in vitro antimicrobial activity showed great agreement, in addition to the docking study of COVID-19 revealed the ability of triazole derivatives to fit in the active site of the protein, which made us recommend laboratory tests for these triazole derivatives to prove their inhibition efficiency.</p

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity

© 2023 The Authors. Published by American Chemical Society.The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools. The compounds demonstrated promising anti-cancer activity for the MCF-7 breast cancer cell line (GI = 6-63%). The compound with the highest activity (6j) was selective for the MCF-7 breast cancer cell line (IC50 = 17.01 μM) with no effect on the MCF-12A normal breast cell line supported by real-time cell analysis. A morphological examination of the used cell lines confirmed a cytostatic effect of compound 6j. It inhibited both in vivo and in vitro estrogenic activity, triggering a 38% reduction in uterine weight induced by estrogen in an immature rat model and hindering 62% of ER-α receptors in in vitro settings. In silico molecular docking and molecular dynamics simulation studies supported the stability of the ER-α and compound 6j protein-ligand complex. Herein, we report that indolin-2-one derivative 6j is a promising lead compound for further pharmaceutical formulations as a potential anti-breast cancer drug