Identification of bioactive compounds of Zanthoxylum armatum as potential inhibitor of pyruvate kinase M2 (PKM2): Computational and virtual screening approaches.

PKM2 (Pyruvate kinase M2) is the isoform of pyruvate kinase which is known to catalyse the last step of glycolysis that is responsible for energy production. This specific isoform is known to be highly expressed in certain cancerous conditions. Considering the role of this protein in various cancer conditions, we used PKM2 as a target protein to identify the potential compounds against this target. In this study, we have examined 96 compounds of Zanthoxylum armatum using an array of computational and in silico tools. The compounds were assessed for toxicity then their anticancer potential was predicted. The virtual screening was done with molecular docking followed by a detailed examination using molecular dynamics simulation. The majority of the compounds showed a higher probability of being antineoplastic. Based on toxicity, predicted anticancer potential, binding affinity, and binding site, three compounds (nevadensin, asarinin, and kaempferol) were selected as hit compounds. The binding energy of these compounds with PKM2 ranged from -7.7 to -8.3 kcal/mol and all hit compounds interact at the active site of the protein. The selected hit compounds formed a stable complex with PKM2 when simulated under physiological conditions. The dynamic analysis showed that these compounds remained attached to the active site till the completion of molecular simulation. MM-PBSA analysis showed that nevadensin exhibited a higher affinity towards PKM2 compared to asarinin and kaempferol. These compounds need to be assessed properties in vivo and in vitro to validate their efficacy.

Identification of anti-cancer organometallic compounds by inhibition of BCL-2/Bax interactions.

Apoptosis is regulated by the BCL-2 family, which includes the anti-apoptotic and pro-apoptotic proteins (Bax, Bok, Bak, etc.). These proteins often interact in dimers and act as apoptotic switches. Anti-apoptotic proteins, such as BCL-2, block the functions of these pro-apoptotic proteins. The pro-apoptotic and anti-apoptotic protein-protein interactions must be inhibited to prevent tumor cells from escaping apoptosis. This method has been used to develop anticancer drugs by inhibiting BCL-2 with both natural and synthetic compounds. Metal-containing compounds were used as pharmaceuticals for human cancer patients for a long time, and cisplatin was the first candidate of this class. Drug design, however, needs to pay more attention to metal complexes. We have studied the X-ray crystal structure of the BCL-2 protein in detail and identified the hydrophobic nature of the site with two less solvent-accessible sites. Based on the hydrophobic nature of the compounds, 74 organometallic compounds with X-ray crystallographically characterized bioactivity (including anticancer activity) were selected from the Cambridge crystallographic database. For testing, molecular docking was used to determine which compound was most effective against the BCL-2 protein. Organometallic compounds (benzene)-chloro-(1-{[(9H-fluoren-2-yl)imino]methyl}naphthalen-2-olato)-ruthenium (2), (1-((1,1'-biphenyl)-4-yl)-2,3,4,5-tetramethylcyclopentadienyl)-chloro-(4,4'-dimethyl-2,2'-bipyridine)-rhodium hexafluorophosphate (37), (µ-1,1'-(butane-1,4-diyl)bis(3-oxy-2-methylpyridin-4(1H)-one))-dichloro-bis(pentamethyl-cyclopentadienyl)-di-rhodium tetrahydrate (46), (µ-1,1'-(butane-1,4-diyl)bis(3-oxy-2-methylpyridin-4(1H)-one))-dichloro-bis(pentamethyl-cyclopentadienyl)-di-iridium (47) etc are found to be important compounds in this study. The capability of different types of complex interactions was identified using Hirshfeld surface analysis of the complexes. A NCI plot was conducted to understand the nature of the interaction between complex amino acids and active-site amino acids. A DFT study was conducted to examine the stability and chemical reactivity of the selected complexes. Using this study, one suitable hydrophobic lead anti-cancer organometallic pharmaceutical was found that binds at the less solvent-accessible hydrophobic site of BCL-2.

Exploration of Psychiatry Residents' Attitudes toward Patients with Substance Use Disorder, Bipolar Disorder and Schizophrenia in Saudi Arabia.

Stigmatizing attitudes of psychiatry professionals toward patients with various mental disorders may negatively impact treatment-seeking behaviors. However, in Saudi Arabia, little is known about psychiatry residents' attitudes toward individuals with a specific disease/disorder. Therefore, the purpose of this study was to assess psychiatry residents' attitudes toward patients with substance use disorder (SUD), bipolar disorder and schizophrenia in Saudi Arabia. Data for this cross-sectional study were collected from psychiatry residents (N = 79) in Saudi Arabia with a structured questionnaire containing sociodemographic and attitude-related variables. The 11-item Medical Condition Regard Scale (MCRS) for individuals with three conditions was used to assess participants' attitudes. A linear regression model was fitted to investigate the association. Based on the MCRS (on a scale of 11 to 66), participants' mean attitude scores were 41.59 (SD: 8.09), 54.53 (SD: 5.90) and 54.20 (SD: 6.60) for SUD, bipolar disorder and schizophrenia, respectively. Adjusted regression analysis demonstrated that senior residents, an age ≥ 27 years and a high confidence level were significantly associated with psychiatry residents' positive attitudes toward patients with the three conditions. Psychiatry residents' attitude scores were relatively lower (i.e., negative attitudes) for patients with SUD than for those with bipolar disorder and schizophrenia. Future longitudinal studies are recommended to explore the factors behind psychiatry residents' negative attitudes toward patients with addictive behaviors and mental illnesses.

Are Saudi Healthcare Workers Willing to Receive the Monkeypox Virus Vaccine? Evidence from a Descriptive-Baseline Survey.

Since Saudi Arabia has already confirmed multiple monkeypox (Mpox) cases, it is essential to initiate timely preventive measures, including the implementation of vaccines. In this cross-sectional study, an online survey was conducted among healthcare workers (HCWs) in Saudi Arabia to understand their willingness to receive the Mpox vaccine. A structured questionnaire was used to gather the data. The study comprised 734 samples. Our study found that among study participants, 52.7% were willing to receive the Mpox vaccine and showed that sociodemographic factors were not significantly associated with vaccine willingness. Previous vaccination history (such as influenza and COVID-19) was significantly associated with Mpox vaccine willingness. The respondents reported that the main reasons for receiving the Mpox vaccine were their trust in the Saudi Health Ministry (57.7%) and their understanding that the vaccine was a social responsibility (44.6%). Furthermore, the majority of the respondents (74.7%) reported that they were motivated by the need to protect themselves, their family and their friends. Insufficient vaccine information and fear of unknown adverse reactions were the most reported reasons for an unwillingness to receive the Mpox vaccine. In conclusion, increasing Mpox vaccine-related awareness and focusing on greater information dissemination to reduce fear and increase vaccine uptake is highly recommended.

Activating the delivery of a model drug to lipid membrane by encapsulation of cyclodextrin: Combined experimental and molecular docking studies.

Drug delivery science is always an important topic as it studies the delivery of therapeutic payloads to the desired target cells without affecting the healthy tissues/cells, thus minimizing drug-induced toxicity. Aiming towards the targeted drug delivery, the present project deals with the delivery of a polarity-sensitive solvatochromic model drug, namely, salt of 8-anilinonaphthalene-1-sulphonic acid (ANSA) to the model bio-membrane (which mimic several aspects of the real cell membrane), more precisely at the lipid-water interface of L-α-Dipalmitoylphosphatidylcholine (DPPC) phospholipid. The drug delivery process has been activated through the binding of dye with cyclodextrin, acting as a drug transporter. Detailed steady-state and time-resolved spectroscopic studies including molecular docking analysis imply the targeted drug delivery of dye, ANSA, towards the lipid-water interface region of lipid bilayers through encapsulation within the cyclodextrin void. Stronger binding interaction of the dye with the lipid bilayers relative to ß-cyclodextrin (ß-CD) is the foremost reason for the targeted delivery. The present biophysical interaction studies of drug-lipid interaction, thus, may provide a cordial approach for drug formulation and drug delivery.

Multifunctional Zn(II) Coordination Polymer as Highly Selective Fluorescent Sensor and Adsorbent for Dyes.

A new Zn(II)-based coordination polymer (1) comprising the Schiff base ligand obtained by the condensation of 5-aminosalicylic acid and salicylaldehyde has been synthesized. This newly synthesized compound has been characterized by analytical and spectroscopic methods, and finally, by single-crystal X-ray diffraction technique in this study. The X-ray analysis reveals a distorted tetrahedral environment around the central Zn(II) center. This compound has been used as a sensitive and selective fluorescent sensor for acetone and Ag+ cations. The photoluminescence measurements indicate that in the presence of acetone, the emission intensity of 1 displays quenching at room temperature. However, other organic solvents caused meagre changes in the emission intensity of 1. Additionally, the fluorescence intensity of 1 has been examined in the presence of different ketones viz. cyclohexanone, 4-heptanone, and 5-nonanone, to assess the interaction between the C=O group of the ketones and the molecular framework of 1. Moreover, 1 displays a selective recognition of Ag+ in the aqueous medium by an enhancement in its fluorescence intensity, representing its high sensitivity for the detection of Ag+ ions in a water sample. Additionally, 1 displays the selective adsorption of cationic dyes (methylene blue and rhodamine B). Hence, 1 showcases its potential as an excellent luminescent probe to detect acetone, other ketones, and Ag+ with an exceptional selectivity, and displaying a selective adsorption of cationic dye molecules.

Comparative Performance Evaluation of the Public Health Surveillance Systems in 6 Gulf Cooperation Countries: Cross-sectional Study.

BACKGROUND: Evaluating public health surveillance systems is important to ensure that events of public health importance are appropriately monitored. Evaluation studies based on the Centers for Disease Control and Prevention (CDC) guidelines have been used to appraise surveillance systems globally. Previous evaluation studies undertaken in member countries of the Gulf Cooperation Council (GCC) were limited to specific illnesses within a single nation. OBJECTIVE: We aimed to evaluate public health surveillance systems in GCC countries using CDC guidelines and recommend necessary improvements to enhance these systems. METHODS: The CDC guidelines were used for evaluating the surveillance systems in GCC countries. A total of 6 representatives from GCC countries were asked to rate 43 indicators across the systems' level of usefulness, simplicity, flexibility, acceptability, sensitivity, predictive value positive, representativeness, data quality, stability, and timeliness. Descriptive data analysis and univariate linear regression analysis were performed. RESULTS: All surveillance systems in the GCC covered communicable diseases, and approximately two-thirds (4/6, 67%, 95% CI 29.9%-90.3%) of them covered health care-associated infections. The mean global score was 147 (SD 13.27). The United Arab Emirates scored the highest in the global score with a rating of 167 (83.5%, 95% CI 77.7%-88.0%), and Oman obtained the highest scores for usefulness, simplicity, and flexibility. Strong correlations were observed between the global score and the level of usefulness, flexibility, acceptability, representativeness, and timeliness, and a negative correlation was observed between stability and timeliness score. Disease coverage was the most substantial predictor of the GCC surveillance global score. CONCLUSIONS: GCC surveillance systems are performing optimally and have shown beneficial outcomes. GCC countries must use the lessons learned from the success of the systems of the United Arab Emirates and Oman. To maintain GCC surveillance systems so that they are viable and adaptable to future potential health risks, measures including centralized information exchange, deployment of emerging technologies, and system architecture reform are necessary.

Antiproliferative Mechanisms of a Polyphenolic Combination of Kaempferol and Fisetin in Triple-Negative Breast Cancer Cells.

Herein, we investigate the combinatorial therapeutic effects of naturally occurring flavonoids kaempferol (K) and fisetin (F) on triple-negative breast cancer (TNBC: MDA-MB-231 cell line). Dose-dependent MTT assay results show that K and F exhibited cytotoxicity in MDA-MB-231 cells at 62 and 75 µM (IC50), respectively, after 24 h. However, combined K + F led to 40% and more than 50% TNBC cell death observed at 10 and 20 µM, respectively, which revealed the synergistic association of both. The combination of K and F was determined to be more effective in inhibiting cell viability than either of the agents alone. The morphological changes associated with significant apoptotic cell death were observed under a fluorescent microscope, strongly supporting the synergistic association between K and F. We also proposed that combining the effects of both polyphenols, as opposed to their individual effects, would increase their in vitro efficacy. Furthermore, we assessed the cell death pathway by the combinational treatment via reactive oxygen species-induced DNA damage and the mitochondrially mediated apoptotic pathway. This study reveals the prominent synergistic role of phytochemicals, which helps in elevating the therapeutic efficacy of dietary nutrients and that anticancer effects may be a result of nutrients that act in concert.

Quantum Computational, Spectroscopic (FT-IR, FT-Raman, NMR, and UV-Vis) Hirshfeld Surface and Molecular Docking-Dynamics Studies on 5-Hydroxymethyluracil (Monomer and Trimer).

For many decades, uracil has been an antineoplastic agent used in combination with tegafur to treat various human cancers, including breast, prostate, and liver cancer. Therefore, it is necessary to explore the molecular features of uracil and its derivatives. Herein, the molecule's 5-hydroxymethyluracil has been thoroughly characterized by NMR, UV-Vis, and FT-IR spectroscopy by means of experimental and theoretical analysis. Density functional theory (DFT) using the B3LYP method at 6-311++G(d,p) was computed to achieve the optimized geometric parameters of the molecule in the ground state. For further investigation and computation of the NLO, NBO, NHO analysis, and FMO, the improved geometrical parameters were utilized. The potential energy distribution was used to allocate the vibrational frequencies using the VEDA 4 program. The NBO study determined the relationship between the donor and acceptor. The molecule's charge distribution and reactive regions were highlighted using the MEP and Fukui functions. Maps of the hole and electron density distribution in the excited state were generated using the TD-DFT method and PCM solvent model in order to reveal electronic characteristics. The energies and diagrams for the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) were also provided. The HOMO-LUMO band gap estimated the charge transport within the molecule. When examining the intermolecular interactions in 5-HMU, Hirshfeld surface analysis was used, and fingerprint plots were also produced. The molecular docking investigation involved docking 5-HMU with six different protein receptors. Molecular dynamic simulation has given a better idea of the binding of the ligand with protein.

Structural, Theoretical Investigations, Hirshfeld Surface Analysis, and Cytotoxicity Profile of a Neocuproine-Co(II)-Based Discrete Homodinuclear Complex.

In this work, we aimed to synthesize a new cobalt(II) complex, namely [Co2(µ-HIPA)(NC)2(H2O)3(NO3)]·(NO3)(C2H5OH)(1) (where H3IPA = 5-hydroxy isophthalic acid and NC = 2,9-dimethyl-1,10-phenanthroline or neocuproine), as a promising chemotherapeutic agent. The diffraction (single crystal-XRD and powder-XRD), spectroscopic (FTIR and UV-visible), molar conductance, and thermal techniques were used to characterize complex 1. Single-crystal X-ray diffraction analysis reveals that Co(II) exists in an octahedral geometry, with the ligation of four oxygen atoms, and two nitrogen atoms. Topological analysis of complex 1 reveals 2,6C6 topological type as an underlying net. The plausible intermolecular interactions within complex 1 that control the crystal packing were analyzed by Hirshfeld surface analysis. In vitro cytotoxicity of complex 1 was evaluated against acute myeloid leukemia (THP-1), colorectal (SW480), and prostate (PC-3) cancer cell lines by utilizing an MTT assay. The result shows that complex 1 can inhibit the growth of cancer cells (THP-1, SW480, and PC-3) at lower inhibitory concentration (IC50) values of > 100, 43.6, and 95.1 µM respectively. The morphological changes induced by complex 1 on THP-1 and SW480 cancer cell lines were carried out with acridine orange/ethidium bromide staining methods. Additionally, comprehensive molecular docking studies were performed to understand the potential binding interactions of complex 1 with different bio-macromolecules.

Knowledge and Attitude Regarding Monkeypox Virus among Physicians in Saudi Arabia: A Cross-Sectional Study.

The growing incidence of human monkeypox cases emphasizes the significance of prevention, early detection, and prompt responses for healthcare providers. The aim of this study was to assess the knowledge and attitudes toward monkeypox infection among physicians, a frontline healthcare worker group, in Saudi Arabia. A cross-sectional survey assessing knowledge and attitudes towards monkeypox infection on multiple-item scales was sent to physicians in Saudi Arabia. The associations between independent factors and either knowledge or attitude were assessed. The final analysis included 398 participants. Approximately 55% of the surveyed participants had a "good knowledge" score about human monkeypox. The adjusted logistic regression analysis showed that being a female physician, working in the private sector, and having information on human monkeypox during medical school or residency years were the only factors associated with a good level of knowledge about human monkeypox. However, physicians' knowledge and attitudes regarding monkeypox infection are inadequate and influenced by various factors. There is a significant knowledge gap between the therapeutic management of monkeypox and its vaccination. Training and knowledge assessments are important, especially when studies show significant improvement in related and specific knowledge.

Identification of 4-acrylamido-N-(pyridazin-3-yl)benzamide as anti-COVID-19 compound: a DFTB, molecular docking, and molecular dynamics study.

Omicron is one of the variants of COVID-19 and continuing member of a pandemic. There are several types of vaccines that were developed around the globe to fight against the virus. However, the world is suffering to find suitable drug candidates for the virus. The main protease (Mpro) enzyme of the virus is the best target for finding drug molecules because of its involvement in viral infection and protein synthesis. ZINC-15 is a database of 750 million commercially available compounds. We find 125 compounds having two aromatic rings and amide groups for non-covalent interactions with active site amino acids and functional groups with the capability to bind -SH group of C145 of Mpro through covalent bonding by a nucleophilic addition reaction. The lead compound (Z144) was identified using molecular docking. The non-covalent interactions (NCI) calculations show the interactions between amino acids present in the active site of the protein and the lead molecules are attractive in nature. The density functional-based tight-binding (DFTB) study of the lead compound with amino acids in the active site indicates that Q190 and Q193 play a very critical role in stabilization. The Michael addition of the acrylamide group of the lead molecule at ß-position is facile because the low energy lowest unoccupied molecular orbital (LUMO) is concentrated on the group. From molecular dynamics during 100 ns, it has come to light that strong non-covalent interactions are key for the stability of the lead inside the protein and such binding can fold the protein. The free energy for this interaction is -42.72 kcal mol-1 which was obtained from MM-GB/SA calculations.

Assessment of Knowledge of Monkeypox Viral Infection among the General Population in Saudi Arabia.

Monkeypox is re-emerging and spreading over the world, posing a serious threat to human life, especially in non-endemic countries, including Saudi Arabia. Due to the paucity of research on knowledge about monkeypox in Saudi Arabia, this study aimed to evaluate the general population's knowledge of monkeypox in a sample of the country. A web-based cross-sectional survey was conducted from 25 May 2022 to 15 July 2022. Participants' knowledge about monkeypox on a 23-item scale and socio-demographic characteristics were gathered in the survey. Pearson's Chi-square test was used to compare knowledge level (categorized into high and low) and explanatory variables. Out of 480, only 48% of the respondents had high knowledge (mean score > 14). Participants' age, marital status, residential region, living in the urban area, education level, employment status, being a healthcare worker, income, and smoking status were significantly associated with the level of knowledge about monkeypox (p < 0.01). Overall, social media (75.0%) was the most frequently reported source from where participants obtained monkeypox-related information followed by TV and radio (45.6%), family or friend (15.6%), and healthcare provider (13.8%). We found that overall knowledge of monkeypox infection was slightly poor among the Saudi population. These findings highlight the urgent need for public education on monkeypox to promote awareness and engage the public ahead of the outbreak.

Construction of a 3D Metal-Organic Framework and Its Composite for Water Remediation via Selective Adsorption and Photocatalytic Degradation of Hazardous Dye.

In this work, a new bimetallic Na(I)-Zn(II) metal-organic framework (MOF), formulated as [Na2Zn3(btc)2(µ-HCOO)2(µ-H2O)8] n (1) (H3btc = benzene tricarboxylic acid), and its composite (ZnO@1) have been successfully synthesized using solvothermal and mechanochemical solid grinding methods. 1 and ZnO@1 were characterized by diffraction [single-crystal X-ray diffraction (XRD) and powder XRD], spectroscopic (ultraviolet-visible diffuse reflectance spectroscopy and Fourier transform infrared spectroscopy), microscopic (transmission electron microscopy), and thermal (thermogravimetric analysis) methods. The surface area and porosity of 1 were determined using a Brunauer-Emmett-Teller analyzer. Single-crystal diffraction of 1 confirms that Na1 and Zn2 have octahedral coordination environments, whereas Zn1 has a tetrahedral coordination geometry. Topological simplification of 1 shows a 3,6-connected kgd net. Na(I)-Zn(II) MOF (1) is crystallized with slight porosity and exhibits good tendency toward the encapsulation of zinc oxide nanoparticles (ZnO NPs). The photocatalytic behaviors of 1 and its composite (ZnO@1) were investigated over MB dye under sunlight illumination with promising degradation efficiencies of 93.69% for 1 and 97.53% for ZnO@1 in 80 min.

Ternary Copper Tungsten Sulfide (Cu2WS4) Nanoparticles Obtained through a Solvothermal Approach: A Bi-Functional Electrocatalyst for the Hydrogen Evolution Reaction (HER) and Oxygen Evolution Reaction (OER).

In this work, Cu2WS4 nanoparticles have been synthesized via a solvothermal decomposition approach using a heterobimetallic single source precursor, WCu2S4(PPh3)3. The single source precursor, WCu2S4(PPh3)3, has been characterized using multinuclear NMR spectroscopy, while Cu2WS4 nanoparticles have been characterized by powder X-ray diffraction (PXRD) for which Rietveld refinement has been performed to authenticate the lattice structure of the decomposed product, Cu2WS4. Furthermore, FESEM and EDAX analyses have been performed to assess the morphology and composition of Cu2WS4. An electrochemical study in acidic as well as basic media suggested that Cu2WS4 nanoparticles possess efficient bifunctional activity towards electrochemical hydrogen as well as oxygen evolution reactions. Linear sweep voltammetry (LSV) performed in 0.5 N H2SO4 indicates an onset potential for the HER of 462 mV and a Tafel slope of 140 mV dec-1. While LSV performed in 0.1 M KOH indicates an onset potential for the OER of 190 mV and a Tafel Slope of 117 mV dec-1.

A Glimpse into the Extraction Methods of Active Compounds from Plants.

Naturally active compounds are usually contained inside plants and materials thereof. Thus, the extraction of the active compounds from plants needs appropriate extraction methods. The commonly employed extraction methods are mostly based on solid-liquid extraction. Frequently used conventional extraction methods such as maceration, heat-assisted extraction, Soxhlet extraction, and hydrodistillation are often criticized for large solvent consumption and long extraction times. Therefore, many advanced extraction methods incorporating various technologies such as ultrasound, microwaves, high pressure, high voltage, enzyme hydrolysis, innovative solvent systems, adsorption, and mechanical forces have been studied. These advanced extraction methods are often better than conventional methods in terms of higher yields, higher selectivity, lower solvent consumption, shorter processing time, better energy efficiency, and potential to avoid organic solvents. They are usually designed to be greener, more sustainable, and environment friendly. In this review, we have critically described recently developed extraction methods pertaining to obtaining active compounds from plants and materials thereof. Main factors that affect the extraction performances are tuned, and extraction methods are chosen in line with the properties of targeted active compounds or the objectives of extraction. The review also highlights the advancements in extraction procedures by using combinations of extraction methods to obtain high overall yields or high purity extracts.

Elucidation of DNA binding interaction of new Cu(II)/Zn(II) complexes derived from Schiff base and L-tryptophan amino acid: a multispectroscopic and molecular docking approach.

Herein, we describe the synthesis, structural elucidation, and DNA interaction of newly synthesized Cu(II) and Zn(II) complexes, i.e., [Cu(SB)(L-trp)(H2O)2]NO3 (1) and [Zn(SB)(L-trp)(H2O)2]NO3 (2) (SB = Schiff base obtained from the reaction between o-vanillin and 2-amino-2-methylpropane-1,3-diol; L-trp = L-tryptophan). From the analysis, a six-coordinated environment around the Cu(II) or Zn(II) center is proposed. The ability of the complexes to bind with calf thymus DNA was examined by optical spectroscopy (UV-vis titrations and steady-state fluorescence emission) and viscosity measurements. The vivid experimental results revealed that complexes 1 and 2 avidly bind to DNA through surface and groove binding modes, albeit with dissimilar intrinsic binding constants (1.54 × 104 and 1.36 × 104 M-1 for 1 and 2, respectively). Both complexes can displace ethidium bromide (EB) to some extent from the intercalated EB-DNA system, resulting in fluorescence quenching. Additional experiments such as [Fe(CN)6]4--induced quenching and thermal melting confirmed the electrostatic and groove binding mode. Furthermore, molecular docking studies verified that both complexes locate in the DNA minor groove by surface binding and were stabilized through weak intermolecular forces. The binding affinity of the lowest energy docked pose was found to be -5.37 kcal/mol for complex 1 and - 5.18 kcal/mol for complex 2. The present work is expected to pave the way for the synthesis of DNA-targeting Cu(II)/Zn(II) metal complexes for the development of chemotherapeutic agents.

Molecular designing, crystal structure determination and in silico screening of copper(II) complexes bearing 8-hydroxyquinoline derivatives as anti-COVID-19.

The pandemic by COVID-19 is hampering everything on the earth including physical and mental health, daily life and global economy. At the moment, there are no defined drugs, while few vaccines are available in the market to combat SARS-CoV-2. Several organic molecules were designed and tested against the virus but they did not show promising activity. In this work we designed two copper complexes from the ligands analogues with chloroquine and hydroxychloroquine. Both the ligands and complexes were well characterized by using various spectroscopic, thermal and X-ray diffraction techniques. Both the complexes as well as ligands were screened through in silico method with the chloroquine and hydroxychloroquine which essentially proved pivotal for successful understanding towards the target protein and their mechanism of action. The results indicated that the balanced hydrophobic and polar groups in the complexes favor their binding in the active site of the viral ADP-ribose-1 monophosphatase enzyme over the parent organic molecules.

Persistent Hypokalemia post SARS-coV-2 infection, is it a life-long complication? Case report.

INTRODUCTION AND IMPORTANCE: SARS-CoV-2 is a novel infection that has affected millions of people around the world. Complications of the infection may affect multiple systems including cardiovascular, neurological, gastrointestinal, urinary, and pulmonary systems. Hypokalemia, which is a life-threatening condition that may lead to arrhythmia and possibly death, has been noticed in more than half of the COVID-19 patients. Further understanding of the disease process and its complications is necessary to guide in preventing the complications from happening in the first place and finding treatment for patients with an already established complications. CASE PRESENTATION: A 34-year old male from Philippines who lives in Saudi Arabia - Riyadh and works as health care provider with no previous history of any medical illness. Presented by himself to the emergency department (ED) with dry cough, shortness of breath, fever, malaise, and fatigability for five days. On examination (RR 25), (T 38.6 °C) and (O2 89% Room air), on auscultation there was a decrease on air entry bilaterally with scattered crepitations, no wheezing or stridor. Covid-19 swab was positive, (Day 1) potassium 2.91 (mmol/L) magnesium (mmol/L) with normal baseline before getting infected. CLINICAL DISCUSSION: Patient while in the hospital was on daily potassium oral and IV replacement with IV magnesium replacement. Investigation showed 24Hr urine potassium 47.3 (mmol/L), 24Hr urine magnesium 5.52 (mmol/L), 24Hr urine Creatinine 9.25 (mmol/L), (TTKG) Transtubular Potassium Gradient 18 and (VBG) PH:7.38, Pco2:44 (mmHg) Po2:55 (mmHg) HCO3:25 (mEq/L). Patient has an increased renal potassium loss with normal VBG on separate days and normal Blood pressure that excludes diseases with associated acidemia or alkalemia. Our patient didn't want to go for any invasive diagnostic procedures and favored to wait for spontaneous recovery. CONCLUSION: We followed up the potassium level of our patient for more than 5 months since he was diagnosed with COVID-19 to find out that he is still having hypokalemia, as well as, hypomagnesemia. Long term complications of COVID-19 infection such as hypokalemia and hypomagnesemia need to be observed and followed up closely to avoid life-threatening arrythmias and seizures. The attention of the scientific community to possible long term or permanent complications is needed to help find preventive measures and treatment for patients with complications.

Ligand substituent effect on the cytotoxicity activity of two new copper(ii) complexes bearing 8-hydroxyquinoline derivatives: validated by MTT assay and apoptosis in MCF-7 cancer cell line (human breast cancer).

In this study, we have examined the effect of ligand substituent on the structure-cytotoxicity relationships of the MCF-7 cancer cell line (human breast cancer), by two copper(ii) complexes {[Cu(qmbn)(Hqmba)(q)]·NO3·2H2O} (1) and {[Cu(Hqmba)2(q)]·NO3·2H2O} (2) (where, qmbn = 2-(quinolin-8-yloxy)(methyl) benzonitrile (L1); Hqmba = 2-((quinolin-8-yloxy)methyl)benzoic acid (L2) and q = quinolin-8-olate). The structural analysis reveals that both the complexes exhibit distorted octahedral (CuN3O3) configuration which is further corroborated by density functional theory (DFT) calculations. The cytotoxicity impact of ligands (L1 and L2) and complexes (1 and 2) was screened against the MCF-7 cell line (human breast cancer). The MTT assay uptake indicated that the presence of -COOH functionality in complex 2 leads to higher cytotoxicity (lower IC50) than that observed for complex 1 containing a -CN group. This could be due to the strong H-bonding forming propensity of the carboxylic acids. Incubation of MCF-7 cancer cells with IC50 concentrations of 1 and 2 promoted cellular detachments via nuclear condensation and membrane destabilization followed by apoptosis as a result of metal-assisted generation of reactive oxygen species. Flow cytometry analysis showed that 1 and 2 might prompt early apoptosis in MCF-7 cells as the maximum percentage of cells appeared in the LR quadrant. Furthermore, mRNA expression analysis confirmed that both the complexes induced apoptosis in MCF-7 cells. Comparative mRNA expression analysis of complexes with their respective ligands also confirmed the enhanced apoptotic behavior of complexes. Furthermore, molecular docking studies of the complexes have also been performed with the active site of EGFR kinase receptors (major target for any cancer causing agent) due to similar analogues with FDA-approved EGFR inhibitors in order to rationalize its promising cytotoxicity activity.