Insights into the Biological Activities and Substituent Effects of Pyrrole Derivatives: The Chemistry-Biology Connection.

Pyrrole, with its versatile heterocyclic ring structure, serves as a valuable template for generating a diverse range of lead compounds with various pharmacophores. Researchers and scientists globally are intrigued by pyrrole and its analogues for their broad pharmacological potential, prompting thorough investigations aimed at advancing human welfare. This comprehensive review delves into the diverse activities exhibited by pyrrole compounds, encompassing their synthesis, reactions, and pharmacological properties alongside their derivatives. In addition to detailing the characteristics of pyrrole and its derivatives within the context of green chemistry, the review also examines microwave-assisted reactions. It provides insights into their chemical structures, natural occurrences, and potential applications across various domains. Furthermore, the article investigates structural alterations of pyrrole compounds and their implications on their functionality, highlighting their versatility as foundational elements for both functional materials and bioactive compounds. Ultimately, the review underscores the imperative for continued research and development in the realm of pyrrole compounds to unearth novel activities and advantages.

Evaluation of Habenaria aitchisonii Reichb. for antioxidant, anti-inflammatory, and antinociceptive effects with in vivo and in silico approaches.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000 mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Investigating Majhool date (Phoenix dactylifera) consumption effects on fasting blood glucose in animals and humans.

OBJECTIVES: Majhool date (Phoenix dactylifera), renowned for its premium taste and texture, is extensively consumed in the Islamic world, particularly during Ramadan. Despite its popularity, concerns persist regarding its potential to induce diabetes in non-patients. This study aims to explore the diabetogenic effects of prolonged Majhool date (Phoenix dactylifera) consumption, the widely used fruit in the Islamic world, through animal experiments and human clinical data. METHODS: Medjool dates were processed into an ethanolic extract for the animal experiment. Then, 21 Balb/c mice received varying doses of the extract for one month. The fasting blood glucose levels were analyzed at the beginning and after one month of consumption of the Majhool date extract. For the clinical study, 387 healthy participants were recruited, with fasting blood glucose levels assessed before and after Ramadan, a period of heightened Majhool date consumption. RESULTS: all groups of the experimental animals exhibited a significant (p<0.05) weight increase after Majhool date consumption, while no significant (p>0.05) alteration in fasting blood glucose levels among groups. In addition, it was found that fasting blood glucose levels remained statistically unchanged (p>0.05) after heightened Majhool date consumption among humans. CONCLUSIONS: The study challenges the belief that Majhool date induces diabetes, supported by both animal and human data. Findings suggest that Majhool date consumption, even at higher doses, does not induce diabetes. Further investigations could explore the impact of other date varieties on the fasting blood glucose levels.

TiO2 nanoparticles: green synthesis, characterization, and investigation of antimicrobial properties, and developmental toxicity in zebrafish (Danio rerio) embryos.

The present study was designed to green synthesize titanium dioxide nanoparticles (G-TiO2 NPs) using Salacia reticulata leaf extract as a reducing and capping agent to assess antidiabetic, anti-inflammatory, and antibacterial effects as well as toxicity evaluation in zebrafish. Besides, zebrafish embryos were employed to study the effect of G-TiO2 NPs on embryonic development. Zebrafish embryos were treated with TiO2 as well as G-TiO2 NPs at four different concentrations, i.e., 25, 50, 100, and 200 µg/ml for 24-96-hour post-fertilization (hpf). The SEM analysis of G-TiO2 NPs confirmed that the size was in the range of 32-46 nm and characterized by EDX, X-ray diffraction (XRD), FTIR, UV-vis spectra. During 24-96-hour post-fertilization (hpf), the results showed that 25-100 µg/ml of TiO2 and G-TiO2 NP instigated developmental acute toxicity in these embryos, causing mortality, hatching delay, and malformation. TiO2 and G-TiO2 NPs exposure induced axis bent, tail bent, spinal cord curvature, yolk-sac, and pericardial edema. Exposure of larvae to the highest concentrations of 200 µg/ml TiO2 and G-TiO2 NPs caused maximum mortality at all time points and reached 70% and 50%, respectively, at 96 hpf. Besides, both TiO2 and G-TiO2 NP revealed antidiabetic and anti-inflammatory effects in vitro. In addition, G-TiO2 NPs exhibited antibacterial effects. Taken together, this study provided a valuable insight into the synthesis of TiO2 NPs using green methods and the synthesized G-TiO2 NPs possess moderate toxicity and potent antidiabetic, anti-inflammatory and antibacterial activities.

Subthreshold Current Suppression in ReS2 Nanosheet-Based Field-Effect Transistors at High Temperatures.

Two-dimensional rhenium disulfide (ReS2), a member of the transition-metal dichalcogenide family, has received significant attention due to its potential applications in field-effect transistors (FETs), photodetectors, and memories. In this work, we investigate the suppression of the subthreshold current during the forward voltage gate sweep, leading to an inversion of the hysteresis in the transfer characteristics of ReS2 nanosheet-based FETs from clockwise to anticlockwise. We explore the impact of temperature, sweeping gate voltage, and pressure on this behavior. Notably, the suppression in current within the subthreshold region coincides with a peak in gate current, which increases beyond a specific temperature but remains unaffected by pressure. We attribute both the suppression in drain current and the presence of peak in gate current to the charge/discharge process of gate oxide traps by thermal-assisted tunnelling. The suppression of the subthreshold current at high temperatures not only reduces power consumption but also extends the operational temperature range of ReS2 nanosheet-based FETs.

Sustainable Pest Management Using Novel Nanoemulsions of Honeysuckle and Patchouli Essential Oils against the West Nile Virus Vector, Culex pipiens, under Laboratory and Field Conditions.

Essential oils are natural plant products that are very interesting, as they are important sources of biologically active compounds. They comprise eco-friendly alternatives to mosquito vector management, particularly essential oil nanoemulsion. Therefore, the aim of this study is to evaluate the effectiveness of 16 selected essential oils (1500 ppm) in controlling mosquitoes by investigating their larvicidal effects against the larvae and adults of the West Nile virus vector Culex pipiens L. (Diptera: Culicidae); the best oils were turned into nanoemulsions and evaluated under laboratory and field conditions. The results show that honeysuckle (Lonicera caprifolium) and patchouli (Pogostemon cablin) essential oils were more effective in killing larvae than the other oils (100% mortality) at 24 h post-treatment. The nanoemulsions of honeysuckle (LC50 = 88.30 ppm) and patchouli (LC50 = 93.05 ppm) showed significantly higher larvicidal activity compared with bulk honeysuckle (LC50 = 247.72 ppm) and patchouli (LC50 = 276.29 ppm) oils. L. caprifolium and P. cablin (100% mortality), followed by Narcissus tazetta (97.78%), Rosmarinus officinalis (95.56%), and Lavandula angustifolia (95.55%), were highly effective oils in killing female mosquitoes, and their relative efficacy at LT50 was 5.5, 5.3, 5.8, 4.1, and 3.2 times greater, respectively, than Aloe vera. The results of the field study show that the honeysuckle and patchouli oils and their nanoemulsions reduced densities to 89.4, 86.5, 98.6, and 97.0% at 24 h post-treatment, respectively, with persistence for eight days post-treatment in pools. Nano-honeysuckle (100% mortality) was more effective than honeysuckle oils (98.0%). Our results show that honeysuckle and patchouli oils exhibited promising larvicidal and adulticidal activity of C. pipiens.

Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.

Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof therapies. In early-stage cervical cancer may not show any symptoms, however, as the cancer progresses, some people may experience- abnormal vaginal bleeding, watery or bloody vaginal discharge, pain in the pelvis or lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved drug library using a multitargeted inhibitory approach against four cervical cancer proteins, namely mitotic arrest deficient -2, DNA polymerase epsilon B-subunit, benzimidazole-related -1, and threonine-protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the Mitoxantrone 2HCl -protein complexes that revealed the formation of stable drug-protein complexes and provided insights into the molecular interactions that contribute to Mitoxantrone's inhibitory effects on these proteins and can be a better drug for cervical cancer. However, experimental studies of these findings could pave the way for therapies to combat cervical cancer effectively.

Does Ramadan Intermittent Fasting Affect the Fasting Blood Glucose Level among Type II Diabetic Patients?

BACKGROUND: The level of fasting blood glucose (FBG) is influenced by several factors, including health status, genetics, and diet. Some studies have reported a beneficial effect of Ramadan Intermittent Fasting (RIF) on diabetic patients. However, clinical observations have shown that diabetes is exacerbated in some patients. AIM: This study aims to investigate the influence of RIF on the FBG level, a biomarker of hyperglycemia and diabetes, and to identify factors associated with variations in FBG levels during RIF among diabetic patients. METHODS: This study is a cross-sectional study. We monitored the FBG levels of 181 type II diabetic patients over a two-month period, from 20 February to 20 April 2023, which represents the Islamic lunar months of Shaban (8th month) and Ramadan (9th month). Ramadan provides a prominent month of intermittent fasting practice for studying its physiological effects on diabetes. We collected clinical data from each participant, including demographic information, co-morbidities, and medications used during this period. RESULTS: Based on our findings, diabetic patients were classified into three groups depending on the influence of RIF on FBG levels: the positively affected group (44%), whose average FBG levels were reduced; the neutrally affected group (24%), whose average FBG levels did not change; and the negatively affected group (32%), whose average FBG levels increased during the fasting month of Ramadan compared to the previous month. Furthermore, we found that the positive effect of RIF was more frequent among obese, non-geriatric, and male diabetic patients, while the negative effect of RIF was more frequent among patients who were not adhering to the medication. CONCLUSIONS: This study concludes that RIF affects FBG levels differently among diabetic patients. These findings should be taken into consideration when treating diabetic patients during the fasting month of Ramadan, and further studies are needed to identify (1) factors associated with inter-individual variation in the response to RIF and (2) those who are great candidates for RIF.

The Effect of Cerebrolysin in an Animal Model of Forebrain Ischemic-Reperfusion Injury: New Insights into the Activation of the Keap1/Nrf2/Antioxidant Signaling Pathway.

Forebrain ischemia-reperfusion (IR) injury causes neurological impairments due to decreased cerebral autoregulation, hypoperfusion, and edema in the hours to days following the restoration of spontaneous circulation. This study aimed to examine the protective and/or therapeutic effects of cerebrolysin (CBL) in managing forebrain IR injury and any probable underlying mechanisms. To study the contribution of reperfusion to forebrain injury, we developed a transient dual carotid artery ligation (tDCAL/IR) mouse model. Five equal groups of six BLC57 mice were created: Group 1: control group (no surgery was performed); Group 2: sham surgery (surgery was performed without IR); Group 3: tDCAL/IR (surgery with IR via permanently ligating the left CA and temporarily closing the right CA for 30 min, followed by reperfusion for 72 h); Group 4: CBL + tDCAL/IR (CBL was given intravenously at a 60 mg/kg BW dose 30 min before IR); and Group 5: tDCAL/IR + CBL (CBL was administered i.v. at 60 mg/kg BW three hours after IR). At 72 h following IR, the mice were euthanized. CBL administration 3 h after IR improved neurological functional recovery, enhanced anti-inflammatory and antioxidant activities, alleviated apoptotic neuronal death, and inhibited reactive microglial and astrocyte activation, resulting in neuroprotection after IR injury in the tDCAL/IR + CBL mice group as compared to the other groups. Furthermore, CBL reduced the TLRs/NF-kB/cytokines while activating the Keap1/Nrf2/antioxidant signaling pathway. These results indicate that CBL may improve neurologic function in mice following IR.

Green synthesis of ZnO-NPs using endophytic fungal extract of Xylaria arbuscula from Blumea axillaris and its biological applications.

The biogenic manufacture of nanoparticles utilising endophytic fungus is an eco-friendly, cost-effective, and secure alternative to constructing chemical methods. The prime focus of the study was to fabricate ZnONPs using the biomass filtrate of endophytic Xylaria arbuscula isolated from Blumea axillaris Linn. and to evaluate their biological properties. The characterisation of the biosynthesized ZnO-NPs was done utilising both spectroscopic and microscopic methods. The bioinspired NPs showed a surface plasmon peak at 370 nm; SEM and TEM micrographs illustrated the hexagonal organisation; XRD spectra proved the crystalline phase as hexagonal wurtzite; EDX analysis confirmed the presence of zinc and oxygen atoms; and the zeta potential analysis proved the stability of ZnONPs. In addition, they also demonstrated significant concentration-dependent inhibition of antimicrobial, antioxidant, anti-inflammatory, and antidiabetic potential in comparison with the reference drugs. In vitro cytotoxicity and wound healing potential of ZnONPs were examined in L929 cell lines, illustrating that they accelerated the wound healing process by roughly 95.37 ± 1.12% after a 24-h exposure to ZnONPs. The photocatalytic activity of the ZnONPs was examined by degrading the methylene blue dye under solar irradiation. In conclusion, our outcomes showed that mycosynthesized ZnONPs possessed potent bioactivity and could be an excellent choice for biomedical applications.

In vitro evaluation of the neuroprotective potential of Olea dioica against Aß peptide-induced toxicity in human neuroblastoma SH-SY5Y cells.

Alzheimer's disease (AD) is a type of neurodegenerative disease, associated with the hastening of ROS, acetylcholinesterase (AChE) activity, and amyloid ß peptides plaques in the brain. The limitations and side effects of existing synthetic drugs incline toward natural sources. In the present communication active principles of methanolic extract of Olea dioica Roxb, leaves are explored as an antioxidant, AChE inhibitor, and anti-amyloidogenic. Furthermore, neuroprotection against the amyloid beta-peptide has been studied. The bioactive principles were identified by GC-MS and LC-MS and further subjected to antioxidant (DPPH and FRAP) and neuroprotection (AChE inhibition, ThT binding, and MTT assay, DCFH-DA and lipid peroxidation (LPO) assay using neuroblastoma (SHSY-5Y) cell lines) assays. Methanolic extract of O. dioica Roxb, leaves was found to contain polyphenols and flavonoids. In vitro assays exhibited potential antioxidant and anti-AChE (˃50%) activities. ThT binding assay indicated protection against amyloid-beta aggregation. MTT assay, Aß1-40 (10 µM) with extract increase the cell viability (˃50%) and showed significant cytotoxicity to SHSY-5Y cells. ROS level (˃25%) significantly decreased in the Aß1-40 (10 µM) + extract (15 and 20 µM/mL) and LPO assay (˃50%) suggesting prevention of cell damage. Results advocate that O. dioica leaves are a good source of antioxidants, anti-AChE, and anti-amyloidogenic compounds which may be further evaluated as a natural medicine for the treatment of AD.

Homozygous Missense Variant in the N-Terminal Region of ANK3 Gene Is Associated with Developmental Delay, Seizures, Speech Abnormality, and Aggressive Behavior.

Introduction: Intellectual disability (ID) is a lifelong disability that affects an individual‧s learning capacity and adaptive behavior. Such individuals depend on their families for day-to-day survival and pose a significant challenge to the healthcare system, especially in developing countries. ID is a heterogeneous condition, and genetic studies are essential to unravel the underlying cellular pathway for brain development and functioning. Methods: Here we studied a female index patient, born to a consanguineous Pakistani couple, showing clinical symptoms of ID, ataxia, hypotonia, developmental delay, seizures, speech abnormality, and aggressive behavior. Whole exome sequencing (WES) coupled with Sanger sequencing was performed for molecular diagnosis. Further, 3D protein modeling was performed to see the effect of variant on protein structure. Results: WES identified a novel homozygous missense variant (c.178T>C; p.Tyr60His) in the ANK3 gene. In silico analysis and 3-dimensional (3D) protein modeling supports the deleterious impact of this variant on the encoding protein, which compromises the protein‧s overall structure and function. Conclusion: Our finding supports the clinical and genetic diversity of the ANK3 gene as a plausible candidate gene for ID syndrome. Intelligence is a complex polygenic human trait, and understanding molecular and biological pathways involved in learning and memory can solve the complex puzzle of how cognition develops. Intellectual disability (ID) is defined as a deficit in an individual‧s learning and adaptive behavior at an early age of onset [American Psychiatric Association, 2013]. It is one of the major medical, and cognitive disorders with a prevalence of 1-3% in the population worldwide [Leonard and Wen, 2002]. ID often exists with other disabling mental conditions such as autism, attention deficit hyperactivity disorder, epilepsy, schizophrenia, bipolar disorder, or depression. Almost half of the cases appear to have a genetic explanation that ranges from cytogenetically visible abnormalities to monogenic defects [Flint, 2001; Ropers, 2010; Tucker-Drob et al., 2013]. Intellectual disability is a genetically heterogeneous condition, and more than 700 genes have been identified to cause ID alone or as a part of the syndrome. Research in X-linked ID has identified more than 100 disease-causing genes on the X chromosome that play a role in cognition; however, research into autosomal causes of ID is still ongoing [Vissers et al., 2016].

PheroxyPyrabenz and Carbopyrropyridin against major proteins of SARS CoV-2: a comprehensive in-silico molecular docking and dynamics simulation studies.

The pandemic that started in 2020 left us with so much information about viruses and respiratory diseases, and the cause behind it was severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). The world is still recovering, which costs so many economic and other indirect disasters; despite that, no medications are available on the market. Although the WHO approved a few vaccines on an emergency basis, the remarks and the reinfection chances are still under investigation, and a few pharmaceutical companies are also claiming that a few medications can be effective. However, there is no situation in control. SARS CoV-2 mutates and comes in different forms, making the situation unpredictable. In this study, we have screened the complete Asinex's BioDesign library, which contains 170,269 compounds, and shorted the data against the docking score that helps in the identification of 4-[5-(3-Ethoxy-4-hydroxyphenyl)-1-(2-hydroxyethyl)-1H-pyrazol-3-yl]-1, 2-benzenediol (PheroxyPyrabenz) and 1-[(3R,4R)-1-(5-Aminopentanoyl)-4-hydroxy-3-pyrrolidinyl]-1H-pyrrolo[2,3-b]pyridine-4-carboxamide (Carbopyrropyridin) as a significant drug candidate that can work against the multiple proteins of the SARS CoV-2 resulting in seizing the complete biological process of the virus. Further, the study extended to Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and molecular dynamics (MD) simulation of both the compounds with their complexity. The complete workflow of the study has shown satisfactory results, and both drug candidates can potentially stop the hunt for drugs against this virus after its experimental validation. Further, we checked both compounds' absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, showing case-proof validatory results.Communicated by Ramaswamy H. Sarma.

A novel biallelic variant in the Popeye domain-containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25.

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb-girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio-whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1Pro134Leu , POPDC1Ile193Ser , and POPDC1Ser201Phe ) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease.

An unusual case of gastric angiolipoma presenting with upper gastrointestinal bleeding.

Gastric angiolipomas (GA) are rare benign tumors that can present with gastrointestinal bleeding and anemia. We describe a 73-year-old woman who presented with a 3-day history of fatiguability, epigastric pain and melena. A computed tomography scan revealed a hypodense lesion, measuring 6 × 6 × 5 cm, along the upper part of the stomach. An upper endoscopy revealed a large polypoid lesion, measuring 8 × 6 cm, between the cardia and body of the stomach. Multiple biopsy specimens were taken, and a histopathological examination showed an acute erosive helicobacter-associated reactive gastritis but no definitive atypia. A linear endoscopic ultrasound revealed a large, homogenous, hyperechoic lesion, consistent with a lipoma, in the body of the stomach. A fine needle aspiration was negative for malignancy. A laparoscopy was offered, and a wedge resection was performed. A histopathological examination revealed a well-circumscribed, encapsulated lipomatous tumor in the gastric submucosa with focal mucosal ulceration. The patient had an uneventful postoperative recovery and her hemoglobin level subsequently returned to normal. Overall, clinicians may be unfamiliar with GA because patients may present with signs and symptoms that can be confused with other gastrointestinal conditions. Physicians should be aware of the characteristic histopathological features to distinguish GA from other diseases of the gastrointestinal tract that may share similar clinical or radiologic features.

Phytochemical Analysis, Total Phenolic, Flavonoid Contents, and Anticancer Evaluations of Solvent Extracts and Saponins of H. digitata.

Cancer is one of the most challenging diseases in the modern era for the researchers and investigators. Extensive research worldwide is underway to find novel therapeutics for prevention and treatment of diseases. The extracted natural sources have shown to be one of the best and effective treatments for cell proliferation and angiogenesis. Different approaches including disc potato model, brine shrimp, and chorioallantoic membrane (CAM) assay were adopted to analyze the anticancer effects. Habenaria digitata was also evaluated for MTT activity against NIH/3T3 cell line. The dexamethasone, etoposide, and vincristine sulfate were used as a positive control in these assays. All of the extracts including crude extracts (Hd.Cr), saponin (Hd.Sp), n-hexane (Hd.Hx), chloroform (Hd.Chf), ethyl acetate (Hd.EA), and aqueous fraction (Hd.Aq) were shown excellent results by using various assays. For example, saponin and chloroform have displayed decent antitumor and angiogenic activity by using potato tumor assay. The saponin fraction and chloroform were shown to be the most efficient in potato tumor experiment, demonstrating 87.5 and 93.7% tumor suppression at concentration of 1000 µg/ml, respectively, with IC50 values of 25.5 and 18.3 µg/ml. Additionally, the two samples, chloroform and saponins, outperformed the rest of the test samples in terms of antiangiogenic activity, with IC50 28.63 µg/ml and 16.20 µg/ml, respectively. In characterizing all solvent fractions, the chloroform (Hd.Chf) and saponin (Hd.Sp) appeared to display good effectiveness against tumor and angiogenesis but very minimal activity against A. tumefaciens. The Hd.Chf and Hd.Sp have been prospective candidates in the isolation of natural products with antineoplastic properties.

Identification of compelling inhibitors of human norovirus 3CL protease to combat gastroenteritis: A structure-based virtual screening and molecular dynamics study.

Human noroviruses (NV) are the most prevalent cause of sporadic and pandemic acute gastroenteritis. NV infections cause substantial morbidity and death globally, especially amongst the aged, immunocompromised individuals, and children. There are presently no authorized NV vaccines, small-molecule therapies, or prophylactics for humans. NV 3 C L protease (3CLP) has been identified as a promising therapeutic target for anti-NV drug development. Herein, we employed a structure-based virtual screening method to screen a library of 700 antiviral compounds against the active site residues of 3CLP. We report three compounds, Sorafenib, YM201636, and LDC4297, that were revealed to have a higher binding energy (BE) value with 3CLP than the control (Dipeptidyl inhibitor 7) following a sequential screening, in-depth molecular docking and visualization, physicochemical and pharmacological property analysis, and molecular dynamics (MD) study. Sorafenib, YM201636, and LDC4297 had BEs of -11.67, -10.34, and -9.78 kcal/mol with 3CLP, respectively, while control had a BE of -6.38 kcal/mol. Furthermore, MD simulations of the two best compounds and control were used to further optimize the interactions, and a 100 ns MD simulation revealed that they form stable complexes with 3CLP. The estimated physicochemical, drug-like, and ADMET properties of these hits suggest that they might be employed as 3CLP inhibitors in the management of gastroenteritis. However, wet lab tests are a prerequisite to optimize them as NV 3CLP inhibitors.

Succinimide Derivatives as Antioxidant Anticholinesterases, Anti-α-Amylase, and Anti-α-Glucosidase: In Vitro and In Silico Approaches.

Based on the diverse pharmacological potency and the structural features of succinimide, this research considered to synthesize succinimide derivatives. Moreover, these compounds were estimated for their biological potential in terms of anti-diabetic, anti-cholinesterase, and anti-oxidant capacities. The compounds were synthesized through Michael addition of various ketones to N-aryl maleimides. Similarly, the MOE software was used for the molecular docking study to explore the binding mode of the potent compounds against different enzymes. In the anti-cholinesterase activity, the compounds MSJ2 and MSJ10 exhibited outstanding activity against acetylcholinesterase (AChE), i.e., 91.90, 93.20%, and against butyrylcholinesterase (BChE), i.e., 97.30, 91.36% inhibitory potentials, respectively. The compounds MSJ9 and MSJ10 exhibited prominent α-glucosidase inhibitory potentials, i.e., 87.63 and 89.37 with IC50 value of 32 and 28.04 µM, respectively. Moreover, the compounds MSJ2 and MSJ10 revealed significant scavenging activity against DPPH free radicals with IC50 values of 2.59 and 2.52, while against ABTS displayed excellent scavenging potential with IC50 values 7.32 and 3.29 µM, respectively. The tentative results are added with molecular docking studies in the active sites of enzymes to predict the theoretical protein-ligand binding modes. Further detailed mechanism-based studies in animal models are essential for the in vivo evaluation of the potent compound.

Effectiveness of Early Favipiravir Therapy in Hospitalised COVID-19 Patients.

COVID-19 is a disease caused by a novel coronavirus with no specific, standard treatment. We investigated the clinical data of COVID-19 patients admitted to King Fahad Specialist Hospital (KFSH) in Buraydah by comparing the patients who were treated early with favipiravir (within 3 days of admission) to patients who were treated after three days of admission or not treated. 165 patients were confirmed with PCR tests and admitted to KFSH for treatment. Comorbidities contributed significantly to increasing the length of stay in hospital at 11.4 ± 0.8 days compared to patients with no comorbidities at 8.6 ± 0.9 days (p=0.041). A total of 103 patients were treated with favipiravir, and we found that early treatment with favipiravir (within 3 days) reduced the length of stay in hospital significantly (8.8 ± 1.4 days) compared to patients who were treated after 3 days (13.3 ± 4.6 days) (p=0.0015). Moreover, patients with comorbidities in both early and late treatment groups had significantly higher average lengths of stay in hospital (11.2 ± 0.9 days) compared to patients with no comorbidities (7.9 ± 0.7 days) (p=0.017). Interestingly, patients treated early with favipiravir (with comorbidities and without) stayed fewer days in hospital compared to those with late treatment (p=0.021; a difference of 4.5 ± 1.9 days; and p=0.018; a difference of 4.2 ± 1.7 days, respectively). In conclusion, our analysis indicates that early treatment with favipiravir can reduce the length of stay in hospital and improve clinical manifestations of COVID-19 patients.

Ultra-sonication-enhanced green synthesis of silver nanoparticles using Barleria buxifolia leaf extract and their possible application.

The main aim of the study, green route to the synthesis of silver nanoparticles (AgNPs) is a new technique that has recently gained popularity due to several advantages over conventional chemical methods. The objective of the study was focused on the green synthesis of AgNPs using Barleria buxifolia leaf extract via a rapid and eco-friendly ultrasonic-assisted technique. The obtained AgNPs were characterized using ultraviolet-visible (UV-Vis) absorption spectrum of the organically reduced silver showed a surface plasmon peak at 435 nm, characteristic for silver colloidal solutions. UV-Vis absorption spectrum, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDS) analysis showed that the obtained AgNPs were dispersed spheres with a uniform size of 80 nm. Furthermore, the Fourier-transform infrared spectroscopy (FTIR) and X-ray powder diffraction (XRD) analysis indicated that the surface of the obtained AgNPs was covered with organic molecules in plant extracts. Green synthesized AgNPs showed the highest antioxidant, antibacterial and anti-biofilm activity than a plant extract. In vitro anticancer assay demonstrated half-maximal inhibitory concentration (IC50) values of 31.42, 30.67, 51.07 and 56.26 µg/mL against MCF-7, HeLa and HepG2 cancer cell lines, respectively, which confirms its potent anticancer action. The biocompatibility of green synthesized AgNPs is confirmed by their lack of cytotoxicity against normal human cells. The potent bioactivity exhibited by the green synthesized AgNPs leads towards the multiple use as antioxidant, antibacterial, anti-biofilm and cytotoxic agent.