Zingiberaceae-derived phytomolecules inhibit Japanese encephalitis virus RNA dependent RNA polymerase: a molecular dynamics study.

The Japanese encephalitis virus, (JEV), is a flavivirus mostly transmitted by Culex mosquitoes mostly present in Southeast Asia and the Western Pacific region. Ardeid-wading birds are the natural reservoir of JEV; nonetheless, pigs are frequently a key amplifying host during epidemics in human populations. Although more domestic animals and wildlife are JEV hosts, it is unclear how these animals fit into the ecology and epidemiology of the virus. Even though there is no specific therapy, vaccines are available to prevent this infection. However, current vaccinations do not work against every clinical isolate and can cause neurological problems in certain people. In this study, we have screened 501 phytochemical compounds from various plants from the Zingeberaceae family against the RdRp protein of JEV. Based on this, the top five compounds (IMPHY014466, IMPHY004928, IMPHY007097, IMPHY014179 and IMPHY005010) were selected based on the obtained docking scores, which was above -8.0 Kcal/mol. Further, the binding affinity of these selected ligands was also analysed using molecular interaction, and the presence of interactions like hydrogen bonds, hydrophobic bonds and polar bonds with respective active residues were identified and studied elaborately. Furthermore, the dynamic stability of the docked RdRp protein with these selected phytochemicals was studied using Molecular dynamic simulation and essential dynamics. The free energy landscape analysis also provided information about the energy transition responsible stability of the complex. The results obtained advocated phytochemical compounds from the zingeberaceae family for future experimental validation, as these compounds exhibited significant potential as JEV antagonists.Communicated by Ramaswamy H. Sarma.

Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome.

The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.

Unraveling Skin Carcinoma: A Comprehensive Examination of Diagnosis, Treatment Strategies, and Emerging Therapeutic Avenues in Skin Cancer Management.

Cancer that begins in the skin is by far the most common kind of skin cancer found everywhere in the globe. It is further subdivided into groups, such as basal cell carcinoma and cutaneous squamous cell carcinoma, in addition to other, less common types of skin cancer. In this article, the diagnostic aspects that need to be taken into consideration when utilizing these new guidelines, go over the essential features of cutaneous SCC, conduct an analysis of recent changes in the category of cutaneous SCC, and speak about recent advancements in the categorization of cutaneous SCC. Over the course of the past decade, photodynamic therapy has developed into a potentially effective treatment for a variety of solid tumors that may be found in people. The combination of metallic nanoparticles and phytoconstituents as a therapy for skin cancer has the potential to be more successful than each treatment used independently. In this article, the various treatment modalities for skin cancer were examined. This included excision surgery, Mohs surgery, radiation therapy, and immunotherapy. These were then followed by targeted therapy or immunotherapy, in addition to surgery, radiation, or photodynamic therapy. Since excision surgery is the most typical procedure used to eradicate skin cancer, we concentrate on it in particular.

A Landscape on Lymphatic Filariasis with its Effects and Recent Advanced Treatments.

Lymphatic filariasis is an infection caused by parasites that poses a significant health, social, and economic burden, affecting a vast population that exceeds 120 million individuals globally. The Etiology of the infection is attributed to three nematode parasites, namely Wuchereria bancrofti, B. timori, and Brugia malayi, as well as which are phylogenetically related. These parasites are transmitted to humans via mosquitoes belonging to the Anopheles, Aedes genera, and Culex. As per the estimation provided by the WHO, the current number of individuals infected with filariasis stands at approximately 120 million across 81 countries. Furthermore, it is estimated that around 1.34 billion individuals reside in regions that are endemic to filariasis, thereby putting them at risk of contracting the disease. Different synthetic drugs such as Ivermectin, Doxycycline, Albendazole, and Suramin are used in the treatment. Some natural plants are Azadirachta indica, Tinospora cordifolia, Zingiber officinal, as well as, some marine sources are also included for better treatment. We also touch briefly on a few additional filarial diseases. Although there are only a few medications available to treat filariasis, their frequent usage may result in drug resistance. Furthermore, there is no effective vaccination for the treatment of filariasis. Due to these restrictions, it has been crucial to create new anti-filarial medications, which motivates researchers to find novel pharmaceuticals with anti-filarial action. In this article, we examine the latest achievements in the anti-filarial area, including the many forms of filariasis and their historical contexts, elimination programmes, various therapeutic classes (both synthetic and natural), investigated product-derived targets as well as clinical investigations.

Nanotechnology-based Herbal Drug Formulation in the Treatment of Diabetes Mellitus.

The utilization of nanotechnology-based herbal medication delivery systems is gaining attention as a novel approach to treating diabetes mellitus. The incorporation of nanotechnology into herbal medicine provides benefits such as enhanced Stability, solubility, and bioavailability of herbal medications. The purpose of this paper is to summarise the present status of research on herbal medicine delivery systems based on nanotechnology for the treatment of diabetic patients. The paper evaluates the various nanocarriers and herbal drugs used, the challenges and opportunities in the development of these systems, and their potential efficacy and safety. Additionally, the paper highlights the need for further research to optimize the formulation and delivery of these systems. This review's overarching objective is to provide a complete understanding of the possibilities of herbal medication delivery systems based on nanotechnology in diabetes mellitus treatment.

Novel hydrazone schiff's base derivatives of polyhydroquinoline: synthesis, in vitro prolyl oligopeptidase inhibitory activity and their Molecular docking study.

This research work reports the synthesis of new derivatives of the hydrazone Schiff bases (1-17) based on polyhydroquinoline nucleus through multistep reactions. HR-ESIMS,1H- and 13C-NMR spectroscopy were used to structurally infer all of the synthesized compounds and lastly evaluated for prolyl oligopeptidase inhibitory activity. All the prepared products displayed good to excellent inhibitory activity when compared with standard z-prolyl-prolinal. Three derivatives 3, 15 and 14 showed excellent inhibition with IC50 values 3.21 ± 0.15 to 5.67 ± 0.18 µM, while the remaining 12 compounds showed significant activity. Docking studies indicated a good correlation with the biochemical potency of compounds estimated in the in-vitro test and showed the potency of compounds 3, 15 and 14. The MD simulation results confirmed the stability of the most potent inhibitors 3, 15 and 14 at 250 ns using the parameters RMSD, RMSF, Rg and number of hydrogen bonds. The RMSD values indicate the stability of the protein backbone in complex with the inhibitors over the simulation time. The RMSF values of the binding site residues indicate that the potent inhibitors contributed to stabilizing these regions of the protein, through formed stable interactions with the protein. The Rg. analysis assesses the overall size and compactness of the complexes. The maintenance of stable hydrogen bonds suggests the existence of favorable binding interactions. SASA analysis suggests that they maintained stable conformations without large-scale exposure to the solvent. These results indicate that the ligand-protein interactions are stable and could be exploited to design new drugs for disease treatment.Communicated by Ramaswamy H. Sarma.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Preparation and evaluation of antidiabetic activity of mangiferin-loaded solid lipid nanoparticles.

This study aimed to develop and optimize mangiferin-loaded solid lipid nanoparticles (MG-SLNs) using the microemulsion technique and ultrasonication. The MG-SLNs were composed of Labrafil M 2130 CS, MG, ethanol, Tween 80, and water. The optimized MG-SLNs exhibited a particle size of 138.37 ± 3.39 nm, polydispersity index of 0.247 ± 0.023, entrapment efficiency of 84.37 ± 2.43 %, and zeta potential of 18.87 ± 2.42 mV. Drug release studies showed a two-fold increase in the release of MG from SLNs compared to the solution. Confocal images indicated deeper permeation of MG-SLNs, highlighting their potential. Molecular docking confirmed mangiferin's inhibitory activity against α-amylase, consistent with previous findings. In vitro studies showed that MG-SLNs inhibited α-amylase activity by 55.43 ± 6.11 %, α-glucosidase activity by 68.76 ± 3.14 %, and exhibited promising antidiabetic activities. In a rat model, MG-SLNs significantly and sustainably reduced blood glucose levels for up to 12 h. Total cholesterol and triglycerides decreased, while high-density lipoprotein cholesterol increased. Both MG-SOL and MG-SLNs reduced SGOT and SGPT levels, with MG-SLNs showing a more significant reduction in SGOT compared to MG-SOL. Overall, the biochemical results indicated that both formulations improved diabetes-associated alterations. In conclusion, the study suggests that loading MG in SLNs using the newly developed approach could be an efficient oral treatment for diabetes, offering sustained blood glucose reduction and positive effects on lipid profiles and liver enzymes.

Optimized Ribociclib nanostructured lipid carrier for the amelioration of skin cancer: Inferences from ex-vivo skin permeation and dermatokinetic studies.

Current research focuses on explicitly developing and evaluating nanostructured lipidic carriers (NLCs) for the chemotherapeutic drug Ribociclib (RCB) via the topical route to surmount the inherent bioavailability shortcomings. The absolute oral bioavailability has not been determined, but using a physiologically based pharmacokinetic model it was predicted that 65.8 % of the standard dose of RCB (600 mg) would be absorbed mainly in the small intestine. RCB-NLCs were produced using the solvent evaporation method, and Box-Behnken Design (BBD) was employed to optimize composition. The prepared NLCs had an average PS of 79.29 ± 3.53 nm, PDI of 0.242 ± 0.021, and a %EE of 86.07 ± 3.14. The TEM analysis disclosed the spherical form and non-aggregative nature of the NLCs. The outcomes of an in-vitro release investigation presented cumulative drug release of 84.97 ± 3.37 % in 24 h, significantly higher than that from the RCB suspension (RCB-SUS). Ex-vivo skin permeation investigations on rodent (Swiss albino mice) revealed that RCB-NLCs have 1.91 times increases in skin permeability comparable to RCB-SUS. Compared to RCB-SUS, RCB-NLCs were able to penetrate deeper into the epidermis membrane than RCB-SUS as per the findings of confocal microscopy. In dermatokinetic study, higher amount of RCB was maintained in both the layers of mice's skin when treated with RCB-NLCs gel comparable to the RCB-SUS gel preparation. The in-vitro, ex-vivo, CLSM, and dermatokinetics data demonstrated a significant possibility for this novel RCB formulation to be effective against skin cancer.

A GIS approach for groundwater quality evaluation with entropy method and fluoride exposure with health risk assessment.

This study used the entropy water quality index to analyse the suitability of groundwater for human consumption as well as the hazard index to identify the probable non-carcinogenic dangers among children, women, and men in Nawada, Bihar (India). A total of 75 groundwater samples were taken from hand pumps and tube/bore wells in the pre-monsoon of 2017, and they were evaluated for various physicochemical characteristics. The region's groundwater major cations and anions are dominated by Ca2+ > Mg2+ and [Formula: see text] > Cl- > [Formula: see text] > NO3- > F > [Formula: see text]. Fluoride, chloride, and hardness exceeded WHO and BIS safe standards. Calcium, sodium, magnesium, sulphate, and chloride showed positive correlations, indicating water-rock interactions and mineral leaching and dissolution. Ionic cross-plots reveal that the dissolution of carbonate minerals was the primary source of calcium and magnesium in the groundwater. Also, silicate weathering contributed to these ions in the groundwater. The entropy water quality index (EWQI) found that 79% of groundwater samples were drinkable, whereas 21% were not consumable. The eastern, western, and some southern study areas have the worst drinking water quality. The main source of fluoride toxicity in people is groundwater. For all sampling locations, the HQ fluoride was calculated to be in the ranges of 0.04-3.69 (male), 0.04-3.27 (female), and 0.05-4 (children), indicating a considerably greater risk than the permissible levels (> 1). The fluoride-based non-carcinogenic risks are 27%, 20%, and 21% for children, women, and men, respectively. Children have higher risks from polluted water than adults, according to the non-carcinogenic health risk assessment. This study establishes a standard for regional and global scientific studies that help decision-makers and planners determine the quality of groundwater and fluoride risk and management.

Investigating the effects of four medicinal plants against dengue virus through QSAR modeling and molecular dynamics studies.

The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔGTotal = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔGTotal = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).Communicated by Ramaswamy H. Sarma.

Synthesis of new bis(dimethylamino)benzophenone hydrazone for diabetic management: In-vitro and in-silico approach.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. Bis(dimethylamino)benzophenone derivatives 1-27 were synthesized from bis(dimethylamino)benzophenone via two-step reaction. Different spectroscopic techniques, including EI-MS and 1H NMR, were employed to characterize all synthetic derivatives. The elemental composition of synthetic compounds was confirmed by elemental analysis and results were found in agreement with the calculated values. The synthetic compounds 1-27 were evaluated for α-glucosidase inhibitory activity, except five compounds all derivatives showed good to moderate inhibitory potential in the range of IC50 = 0.28 ± 2.65 - 0.94 ± 2.20 µM. Among them, the most active compounds were 5, 8, 9, and 12 with IC50 values of 0.29 ± 4.63, 0.29 ± 0.93, 0.28 ± 3.65, and 0.28 ± 2.65, respectively. Furthermore, all these compounds were found to be non-toxic on human fibroblast cell lines (BJ cell lines). Kinetics study of compounds 8 and 9 revealed competitive type of inhibition with Ki values 2.79 ± 0.011 and 3.64 ± 0.012 µM, respectively. The binding interactions of synthetic compounds were also confirmed through molecular docking studies that indicated that compounds fit well in the active site of enzyme. Furthermore, a total of 30ns MD simulation was carried out for the most potent complexes of the series. The molecular dynamics study revealed that compound-8 and compound-12 were stable during the MD simulation.

Cracking the Code of Lumpy Skin Disease: Identifying Causes, Symptoms and Treatment Options for Livestock Farmers.

The novel bovine viral infection known as lumpy skin disease is common in most African and Middle Eastern countries, with a significant likelihood of disease transfer to Asia and Europe. Recent rapid disease spread in formerly disease-free zones highlights the need of understanding disease limits and distribution mechanisms. Capripox virus, the causal agent, may also cause sheeppox and Goatpox. Even though the virus is expelled through several bodily fluids and excretions, the most common causes of infection include sperm and skin sores. Thus, vulnerable hosts are mostly infected mechanically by hematophagous arthropods such as biting flies, mosquitoes, and ticks. As a result, milk production lowers, abortions, permanent or temporary sterility, hide damage, and mortality occur, contributing to a massive financial loss for countries that raise cattle. These illnesses are economically significant because they affect international trade. The spread of Capripox viruses appears to be spreading because to a lack of effectual vaccinations and poverty in rural areas. Lumpy skin disease has reached historic levels; as a consequence, vaccination remains the only viable option to keep the illness from spreading in endemic as well as newly impacted areas. This study is intended to offer a full update on existing knowledge of the disease's pathological characteristics, mechanisms of spread, transmission, control measures, and available vaccinations.

Neuroprotective potential of Afzelin: A novel approach for alleviating catalepsy and modulating Bcl-2 expression in Parkinson's disease therapy.

The lost dopaminergic neurons in the brain prevent mobility in Parkinson's disease (PD). It is impossible to stop the disease's progress by means of symptoms management. Research focuses on oxidative stress, mitochondrial dysfunction, and neuronal degeneration. Exploration of potential neuroprotective drugs against prosurvival B-cell lymphoma 2 (Bcl-2) protein is ongoing. An investigable cause behind PD, as well as preventive measures, could be discovered considering the association between such behavioural manifestations (cataleptic behaviours) and PD. The compound Afzelin, known to guard the nervous system, was chosen for this study. The study was done on rats divided into six different groups. First, there was a control group. The other group was treated with Reserpine (RES) (1 mg/kg). The third group received RES (1 mg/kg) and levodopa (30 mg/kg). The remaining three groups were given RES (1 mg/kg) in conjunction with Afzelin at the following doses: 5 mg/kg, 10 mg/kg, and 20 mg/kg. Cataleptic behavior and mobility in rats was assessed using the rotarod, open field, and modified forced-swim tests. thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), biogenic amines, and Bcl-2 level in rat tissue homogenates were considered. According to the study's findings, the rats treated through co-administration of RES and Afzelin improved significantly in their cataleptic behaviours and locomotor activity. In addition, administering Afzelin itself caused Bcl-2 expression, which could have some neuroprotection properties. This study provides meaningful information on the effectiveness of Afzelin in handling catalepsy and other degenerative neurologic disorders. As a result, other studies need to be conducted to establish the reasons behind the reactions and determine the long-term effects of Afzelin on these conditions.

Identification of common candidate genes and pathways for Spina Bifida and Wilm's Tumor using an integrative bioinformatics analysis.

Spina Bifida (SB) and Wilm's Tumor (WT) are conditions, both associated with children. Several studies have shown that WT later develops in SB patients, which led us to elucidate common key genes and linked pathways of both conditions, aimed at their concurrent therapeutic management. For this, integrated bioinformatics analysis was employed. A comprehensive manual curation of genes identified 133 and 139 genes associated with SB and WT, respectively, which were used to construct a single protein-protein interaction (PPI) network. Topological parameters analysis of the network showed its scale-free and hierarchical nature. Centrality-based analysis of the network identified 116 hubs, of which, 6 were called the key genes attributed to being common between SB and WT besides being the hubs. Gene enrichment analysis of the 5 most essential modules, identified important biological processes and pathways possibly linking SB to WT. Additionally, miRNA-key gene-transcription factor (TF) regulatory network elucidated a few important miRNAs and TFs that regulate our key genes. In closing, we put forward TP53, DICER1, NCAM1, PAX3, PTCH1, MTHFR; hsa-mir-107, hsa-mir-137, hsa-mir-122, hsa-let-7d; and YY1, SOX4, MYC, STAT3; key genes, miRNAs and TFs, respectively, as the key regulators. Further, MD simulation studies of wild and Glu429Ala forms of MTHFR proteins showed that there is a slight change in MTHFR protein structure due to Glu429Ala polymorphism. We anticipate that the interplay of these three entities will be an interesting area of research to explore the regulatory mechanism of SB and WT and may serve as candidate target molecules to diagnose, monitor, and treat SB and WT, parallelly.Communicated by Ramaswamy H. Sarma.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 µM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation.

Background: Novel α-amylase inhibitors play a crucial role in managing diabetes and obesity, contributing to improved public health by addressing these challenging and prevalent conditions. Moreover, the synthesis of anti-oxidant agents is essential due to their potential in combating oxidative stress-related diseases and promoting overall health. Objective: Synthesis of thoisemicarbazone derivatives of 2,4-dichlorophenyl acetic acid and to screened them for their biological activities. Method: Thiosemicarbazone derivatives (4-13) were synthesized by refluxing 2,4-dichlorophenyl acetic acid with sulfuric acid in ethanol to get the ester (2), which was further refluxed with thiosemicarbazide to get compound (3). Finally, different aromatic aldehydes were refluxed with compound (3) in ethanol in catalytic amount of acetic acid to obtained the final products (4-13). Using modern spectroscopic techniques including HR-ESI-MS, 13C-, and 1H NMR, the structures of the created derivatives were confirmed. Results: The synthesized derivatives showed excellent to good inhibitory activity in the range of IC50 values of 4.95 ± 0.44 to 69.71 ± 0.05 µM against α-amylase enzyme when compared to standard drug acarbose (IC50 = 21.55 ± 1.31 µM). In case of iron chelating activity, these products showed potent activity better than standard EDTA (IC50 = 66.43 ± 1.07 µM) in the range of IC50 values of 22.43 ± 2.09 to 61.21 ± 2.83 µM. However, the obtained products also show excellent to good activity in the range of IC50 values of 28.30 ± 1.17 to 64.66 ± 2.43 µM against hydroxyl radical scavenging activity when compared with standard vitamin C (IC50 = 60.51 ± 1.02 µM). DFT used to calculate different reactivity factors including ionization potential, electronegativity, electron affinity, chemical softness, and chemical hardness were calculated using frontier molecular orbital (FMO) computations. The molecular docking studies for the synthesized derivatives with α-amylase were carried out using the AutoDock Vina to understand the binding affinities with active sites of the protein.

Computational exploration of Zika virus RNA-dependent RNA polymerase inhibitors: a promising antiviral drug discovery approach.

The emergence of the Zika virus, which belongs to the Flaviviridae family, became a significant worldwide health issue due to its link with severe neurological complications. The RNA-dependent RNA polymerase (RdRp) of the Zika virus plays a significant part in the replication of the virus and is considered a promising candidate for antiviral drug identification. In this study, we employed computer-based drug discovery approaches to identify potential natural compounds that could act as inhibitors against the RdRp protein of the Zika virus. A comprehensive virtual screening strategy was implemented using the MTiOpenScreen webserver to identify natural compounds from the NP-Lib database. Four natural compounds having the ZINC ID - ZINC000253499147, ZINC000299817665, ZINC000044404209, and ZINC000253388535 were selected based on the binding score revealed during virtual screening. Molecular docking simulations of these selected compounds and reference compounds were performed to assess the binding affinities and the molecular bonds formed during the docking. Additionally, molecular dynamics (MD) simulations, endpoint free binding energy calculation and principal component analysis (PCA) were performed to evaluate the stability and dynamics of the protein-ligand complexes. These compounds exhibited favourable binding energies and formed stable interactions within the active site of the RdRp protein. Moreover, the molecular dynamics simulations revealed the robustness of the protein-ligand complexes, suggesting the potential for sustained inhibition. These findings provide valuable insights for the design and development of novel therapeutic interventions against Zika virus infection. Further experimental validation and optimization of the identified compounds are warranted to advance their potential translation into effective antiviral drugs.Communicated by Ramaswamy H. Sarma.

Polyhydroquinoline derivatives for diabetic management: synthesis, in vitro and in silico approaches.

Background: Medication used to treat Type 2 diabetes by decreasing the absorption of carbohydrates in the intestine consists of α-glucosidase inhibitors. Polyhydroquinoline derivatives have attracted interest as excellent antidiabetic agents. Methods: Polyhydroquinoline derivatives (1-17) were synthesized and tested for in vitro α-glucosidase inhibitory activity. Results: All the synthesized compounds exhibited excellent to good inhibitory activity, having IC50 values from 1.23 ± 0.03 to 73.85 ± 0.61 µM, compared with the standard drug, acarbose. The binding mechanism of these derivatives with α-glucosidase was deduced by docking studies and indicated that a slight variation in the orientation of compounds, affects their binding capability. Conclusion: In order to find new antidiabetic drugs, this study has discovered prospective lead candidates.

Neuroprotective evaluation of diospyrin against drug-induced Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease linked to memory impairment. A current investigation was performed to assess the neuroprotective effect of Diospyrin, a novel therapeutic agent, for the curing of Alzheimer's disease. For this purpose, in-vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory assays and antioxidant studies were conducted, whereas in-vivo studies involved different behavioral animal models tests such as elevated plus maze (EPM), morris water maze (MWM) and paddling Y-maze test. Results of the in-vitro analysis showed IC50 values of 95 µg/mL for AChE and 110 µg/mL for BChE as compared to the standard drug donepezil (IC50: 95 & 85 µg/mL, respectively). DPPH antioxidant assay showed a maximum of 72.85% inhibition (IC50: 139.74 µg/mL) of DPPH-free radicals at the highest concentration of 1000 µg/mL as compared to the ascorbic acid (IC50: 13.72 µg/mL). Moreover, the in-vivo analysis revealed that diospyrin treatment demonstrated gradual betterment in memory and enhanced motor functionality. On the other hand, the computational analysis also showed that the diospyrin had exceptional binding affinities for both AChE and BChE enzymes. In the net shell, it may be deduced that our compound diospyrin could be a valuable drug candidate in managing neurodegenerative disorders like AD.