Potent Inhibitor Of Enzyme Research Articles

In Vitro Evaluation of Antioxidant, Antimicrobial, Cytotoxic, Anti-Inflammatory, Anti-Aging, Enzyme Inhibition Potential, and HPLC Analysis of Traditionally Used Plant Delphinium Uncinatum Wall

In Vitro Evaluation of Antioxidant, Antimicrobial, Cytotoxic, Anti-Inflammatory, Anti-Aging, Enzyme Inhibition Potential, and HPLC Analysis of Traditionally Used Plant Delphinium Uncinatum Wall

Enzyme inhibitory potential of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II enzymes: an in vitro and molecular docking study

In this study, the in vitro effects of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II were investigated. A series of N-methylindole hydrazide/hydrazone derivatives (1a-1t) were tested on these enzymes. The interactions of the synthesized indole derivatives with target enzymes were studied by molecular docking methodology. The results revealed that indole derivative Schiff base compounds inhibited the enzymes significantly. Ki values for hCAI isoenzyme were determined to be in the range of 36.18 ± 3.07–224.29 ± 5.78 nM; for the hCAII isoenzyme in the range of 31.30 ± 2.63–201.64 ± 7.25 nM; for acetylcholinesterase in the range of 6.82 ± 0.72–110.30 ± 9.26 nM. Compared to the control compound Acetazolamide (AZA), 1k and 1p were found to have the best inhibitory effect for hCAI; 1p was found to be the best inhibitory effect for hCAII. Compared to the control compound Tacrine (TAC), 1s showed the best inhibitory effect for AChE. In vitro results were verified with the results obtained by docking studies and interactions with enzymes were demonstrated. Communicated by Ramaswamy H. Sarma

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N-Acetylamino Malonic Acid Derivatives.

Broad application of α,α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available N-acetylamino malonic acid monoesters under Hofer-Moest reaction conditions. The decarboxylative cyclization proceeds under constant current conditions in an undivided cell in an aqueous medium without any added base. A successful bioisosteric replacement of the 1-aminocyclohexane-1-carboxylic acid subunit by the THP-containing amino acid scaffold in cathepsin K inhibitor balicatib helped to reduce lipophilicity while retaining low nanomolar enzyme inhibitory potency and comparable microsomal stability.

Asymmetric Transfer Hydrogenation as a Key Step in the Synthesis of the Phosphonic Acid Analogs of Aminocarboxylic Acids.

α-Aminophosphonic acids have a remarkably broad bioactivity spectrum. They can function as highly efficient transition state mimics for a variety of hydrolytic and angiotensin-converting enzymes, which makes them interesting target structures for synthetic chemists. In particular, the phosphonic acid analogs to α-aminocarboxylic acids (Pa AAs) are potent enzyme inhibitors, but many of them are only available by chiral or enzymatic resolution; sometimes only one enantiomer is accessible, and several have never been prepared in enantiopure form at all. Today, a variety of methods to access enantiopure α-aminophosphonic acids is known but none of the reported approaches can be generally applied for the synthesis of Pa AAs. Here we show that the phosphonic acid analogs of many (proteinogenic) α-amino acids become accessible by the catalytic, stereoselective asymmetric transfer hydrogenation (ATH) of α-oxo-phosphonates. The highly enantioenriched (enantiomeric excess (ee) ≥ 98 %) α-hydroxyphosphonates obtained are important pharmaceutical building blocks in themselves and could be easily converted to α-aminophosphonic acids in most studied cases. Even stereoselectively deuterated analogs became easily accessible from the same α-oxo-phosphonates using deuterated formic acid (DCO2 H).

Design, synthesis, biological activities, and evaluation of molecular docking-dynamics studies of new thiosemicarbazones that may be effective against Alzheimer's disease.

Donepezil is one of the most used drugs in the treatment of Alzheimer's disease. Its activity as an AChE inhibitor makes new studies with these enzyme inhibitors attractive. For this purpose, in this study, 12 compounds including thiosemicarbazone pharmacophore, have been synthesized for the treatment of the Alzheimer's disease. 3,4-Dimethoxybenzene or 1,3-benzodioxolone rings were used for the PAS region. The substituted piperazine benzene structure is preferred for the CAS region. At the same time, the thiosemicarbazone pharmacophore structure with known ChE enzyme inhibition potential was used as a bridge connecting the CAS and PAS regions. Structure determination of compounds 3a-3l were revealed using 13 C-NMR, 1 H-NMR, and HRMS spectroscopic methods. The inhibition profile of obtained compounds (3a-3l) against ChE was evaluated using in vitro modified Ellman method. Compounds 3a, 3b, 3f, 3g and 3i exhibited inhibitory activity against the AChE enzyme. Compound 3a showed the highest inhibitory potential with an IC50 = 0.030 ± 0.001 μM. As a result of molecular docking studies, compound 3a displayed important interactions compared to other active derivatives. Molecular dynamics studies are important to see the stability of the complex formed by ligand and protein. RMSD, RMSF ang Rg parameters were calculated via dynamic studies. In conclusion, compound 3a may be a potential AChE enzyme inhibitor with its strong inhibitory potential and behavior in silico.

Design, synthesis, and molecular docking studies of benzimidazole-1,3,4-triazole hybrids as carbonic anhydrase I and II inhibitors.

In this study, with an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of 10 novel 2-(4-(4-ethyl-5-(2-(substitutedphenyl)-2-oxo-ethylthio)-4H-1,2,4-triazol-3-yl)-phenyl)-5,6-dimethyl-1H-benzimidazole (5a-5j) derivatives and characterized by 1 H-NMR, 13 C-NMR, and HRMS. These compounds were evaluated for their inhibitory activity against hCA I and hCA II. All the compounds exhibited good hCA I and hCA II inhibitory activities with IC50 values in range of 1.288 μM-3.122 μM. Among all these compounds, compound 5e, with an IC50 value of 1.288 μM is the most active against carbonic hCA I. Compound 5h with an IC50 value of 1.532 μM is the most active against carbonic hCA-II. Compounds 5a-5j were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. The compounds were also analyzed for their antioxidant capacity by TAS, FRAP, and DPPH activity. Enzyme inhibition kinetics showed all compounds 5a-5j to inhibit the enzyme by non-competitive. The most active compound 5e for hCA I and compound 5h for hCA-II were subjected to molecular docking, which revealed their binding interactions with the enzyme's active site, confirming the experimental findings.

A comprehensive assessment of phytochemicals from Phyla nodiflora (L.) Greene as a potential enzyme inhibitor, and their biological potential: An in-silico, in-vivo, and in-vitro approach

This work explored Phyla nodiflora (L.) Greene as a potential source of the bioactive medicinal agent. In this aspect, methanol (PN-M) and dichloromethane (PN-D) extracts were prepared from the whole plant and evaluated for phytochemical composition (total bioactive contents, UHPLC-MS analysis, and HPLC-PDA polyphenolic quantification), biological (antioxidant and enzyme inhibition) potential and in-vivo toxicity. The PN-M was found to contain higher phenolic (26.08 mg GAE/g extract) and flavonoid (50.25 mg QE/g extract) contents which might correlate to the higher radical scavenging (DPPH: 52.94 mg TE/g extract; ABTS: 72.11 mg TE/g extract) and reducing power (FRAP: 71.96 mg TE/g extract; CUPRAC: 142.65 mg TE/g extract) antioxidant potential, as well as AChE (4.33 mg GALAE/g extract), tyrosinase (125.36 mg KAE/g extract), and amylase (1.86 mmol ACAE/g extract) inhibition activity of this extract. In contrast, the PN-D extract was found to be most active for phosphomolybdenum (1.30 mg TE/ g extract) and metal chelation (54.84 mg EDTAE/g extract) assays in addition to BChE (4.70 mg GALAE/g extract) and glucosidase (0.62 mmol ACAE/g extract) enzyme inhibition activity. The PN-M extract on UHPLC-MS analysis revealed the tentative identification of 24 different secondary metabolites, most of which belonged to the flavonoid, glycoside, and terpenoid classes of phytochemicals. The polyphenolic composition of the extracts was appraised by HPLC-PDA. Seven phenolic compounds were identified in the extracts. PN-M was found to be rich in catechin (0.25 µg/extract) and 3-OH benzoic acid (0.64 µg/extract), while PN-D contained epicatechin (0.30 µg/extract), 3-OH-4-MeO benzaldehyde (0.21 µg/extract), and 2,3-Di-Meo benzoic acid (0.97 µg/extract) in higher amounts. The methanol extract was found to be non-toxic even at higher doses. Furthermore, the relationship between the phytochemicals and the tested enzymes was highlighted by molecular docking studies. In sum, this research showed that the studied extracts were effective as enzyme inhibitors and antioxidants, suggesting it would be worth investigating in more depth for further advanced studies to explore its pharmacological properties.

Synthesis, in-vitro inhibition of cyclooxygenases and in silico studies of new isoxazole derivatives.

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski's rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.

Evaluation of synthetic aminoquinoline derivatives as urease inhibitors: in vitro, in silico and kinetic studies.

Background: Quinoline and acyl thiourea scaffolds have major chemical significance in medicinal chemistry. Quinoline-based acyl thiourea derivatives may potentially target the urease enzyme. Materials & methods: Quinoline-based acyl thiourea derivatives 1-26 were synthesized and tested for urease inhibitory activity. Results: 19 derivatives (1-19) showed enhanced urease enzyme inhibitory potential (IC50=1.19-18.92μM) compared with standard thiourea (IC50=19.53±0.032μM), whereas compounds 20-26 were inactive. Compounds with OCH3, OC2H5, Br and CH3 on the aryl ring showed significantly greater inhibitory potential than compounds with hydrocarbon chains of varying length. Molecular docking studies were conducted to investigate ligand interactions with the enzyme's active site. Conclusion: The identified hits can serve as potential leads against the drug target urease in advanced studies.

Deep-sea fungal metabolites as potential inhibitors of glucose-regulatory enzymes: In silico structure–activity analysis

Chronic diabetes mellites related hyperglycemia is a major cause of mortality and morbidity due to further complications like retinopathy, hypertension and cardiovascular diseases. Though several synthetic anti-diabetes drugs specifically targeting glucose-metabolism enzymes are available, they have their own limitations, including adverse side-effects. Unlike other natural or marine-derived pharmacologically important molecules, deep-sea fungi metabolites still remain under-explored for their anti-diabetes potential. We performed structure-based virtual screening of deep-sea fungal compounds selected by their physiochemical properties, targeting crucial enzymes viz., α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B involved in glucose-metabolism pathway. Following molecular docking scores and MD simulation analyses, the selected top ten compounds for each enzyme, were subjected to pharmacokinetics prediction based on their AdmetSAR- and pharmacophore-based features. Of these, cladosporol C, tenellone F, ozazino-cyclo-(2,3-dihydroxyl-trp-tyr), penicillactam and circumdatinG were identified as potential inhibitors of α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B, respectively. Our in silico data therefore, warrants further experimental and pharmacological studies to validate their anti-diabetes therapeutic potential.

Betaxolol as a Potent Inhibitor of NDM-1-Positive E. coli That Synergistically Enhances the Anti-Inflammatory Effect in Combination with Meropenem.

With significant human and economic losses, increasing bacterial resistance is a serious global threat to human life. Due to their high efficacy, broad spectrum, and cost-effectiveness, beta-lactams are widely used in the clinical management of bacterial infection. The emergence and wide spread of New Delhi metallo-β-lactamase (NDM-1), which can effectively inactivate β-lactams, has posed a challenge in the design of effective new antimicrobial treatments. Medicine repurposing is now an important tool in the development of new alternative medicines. We present a known glaucoma therapeutic, betaxolol (BET), which with a 50% inhibitory concentration (IC50) of 19.3 ± 0.9 μM significantly inhibits the hydrolytic activity of the NDM-1 enzyme and may represent a potential NDM-1 enzyme inhibitor. BET combined with meropenem (MEM) showed bactericidal synergism in vitro. The efficacy of BET was further evaluated against systemic bacterial infections in BALB/c mice. The results showed that BET+MEM decreased the numbers of leukocytes and inflammatory factors in peripheral blood, as well as the organ bacterial load and pathological damage. Molecular docking and kinetic simulations showed that BET can form hydrogen bonds and hydrophobic interactions directly with key amino acid residues in the NDM-1 active site. Thus, we demonstrated that BET inhibited NDM-1 by competitively binding to it and that it can be developed in combination with MEM as a new therapy for the management of infections caused by medicine-resistant bacteria.

Synthesis of novel coumarin-hydrazone hybrids as α-glucosidase inhibitors and their molecular docking studies.

Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. α-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1H-NMR, 13C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro α-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC50 values ranging between 2.39-57.52 μM, as compared to the standard inhibitor, acarbose (IC50 = 873.34 ± 1.67 μM). Among them, compound 7c is the most potent α-glucosidase inhibitor (IC50 = 2.39 ± 0.05 μM). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the α-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management.

Secondary metabolite profiling, antioxidant capacity, enzyme inhibitory potential and in silico studies of Launaea intybacea (Jacq.) Beauverd: A multifunctional approach to probe into the new nutraceuticals

Regular intake of bioactive components in herbal supplements and functional foods exert significant long-term health promoting effects; however, there is limited knowledge about medicinal potential of many wild plants. Launaea intybacea, growing in Cholistan Desert is being used in folk medicine system without authentication. In the present study dry powdered of L. intybacea was extracted separately with methanol, n-hexane, ethyl acetate and water. The methanolic extract (LI-M) afforded equal phenolic (20.68 ± 0.19 mgGAE/g extract) and flavonoid (20.92 ± 0.17 mgQE/g extract), whereas, hexane (LI-H) and ethyl acetate (LI-E) extracts showed the highest phenolic contents with values as 25.30 ± 0.14 and 25.38 ± 0.48 mg GAE/g extract, respectively, and LI-E showed significant flavonoid content (12.42 ± 0.29 mg GAE/g extract). The LI-M exhibited good inhibitory activity against DPPH and ABTS free radical (30.67 ± 0.07 and 58.28 ± 4.98 mg TE/g extract, respectively), while the LI-E showed free radical inhibitory values as 11.74 ± 0.27 and 44.79 ± 1.56 mg TE/g extract, respectively. LI-H only displayed significant inhibitory value (28.19 ± 1.24 mg TE/g extract) against ABTS radical. The highest CUPRAC activity (86.22 ± 1.35 mg TE/g extract) was also associated with LI-H, while LI-M and LI-E also showed significant activity with the values as 78.77 ± 0.88 and 76.77 ± 1.08 mg TE/g extract, respectively. FRAP activity was nearly equally associated with LI-M, LI-H and LI-E in the range of 47.46 to 40.07 mg TE/g extract, whereas, the phosphomolybdenum and metal chelating activities were observed higher for LI-H (1.29 ± 0.05 mmol TE/g extract and 27.48 ± 0.32 mg EDTAE/g extract, respectively, followed by LI-E. In enzyme inhibition assay, all the extracts were equally active (3.94 to 3.41 mg GALAE/g extract) against AChE, while LI-H showed the highest inhibitory values of 5.13 ± 0.28 mg GALAE/g extract against BChE. Against tyrosinase, the LI-M showed inhibitory value as 46.94 ± 1.53 mg KAE/g extract, while against α-amylase and α-glucosidase, the higher values (0.58 ± 0.02 and 1.80 ± 0.01 mmol ACAE/g extract, respectively) were associated with LI-E. UHPLC-MS analysis disclosed 102 secondary metabolites comprising of various classes. The above results authenticate medicinal use of Launaea intybacea (Jacq.) Beauverd and proposed the use of its extracts in nutraceutical and health promoting formulations.

Functional and Bioactive Properties of Wheat Protein Fractions: Impact of Digestive Enzymes on Antioxidant, α-Amylase, and Angiotensin-Converting Enzyme Inhibition Potential.

This research aimed to determine the biofunctional properties of wheat flour (WF) protein fractions and modifications to the antioxidant, anti-α-amylase and anti-angiotensin-I converting enzyme (ACE) activities induced by the action of digestive endopeptidases in vitro. A molecular characterization of the most abundant protein fractions, i.e., albumins, glutelins-1, glutelins-2 and prolamins, showed that low- and high-MW polypeptides rich in cysteine, glutamic acid and leucine were present in albumins and glutelins, whereas low-MW subunits with a high proportion of polar amino acids prevailed in prolamins. Prolamins exhibited the second-highest water holding capacity (54%) after WF (84%), while albumins provided superior foam stability (76%). Prolamins, glutenins-1 and globulins demonstrated the highest antioxidant activity (up to 95%, 68% and 59%, respectively) both before and after hydrolysis with pepsin (P-H) or trypsin-chymotrypsin (TC-H). Prolamins, globulins and WF strongly inhibited α-amylase (>90%) before and after TC-H, and before P-H (55-71%). Moreover, P-H significantly increased α-amylase inhibition by albumins from 53 to 74%. The fractions with strong ACE inhibitory activity (70-89%) included prolamins and globulins after TC-H or P-H, as well as globulins before TC-H and WF before P-H. This novel evidence indicates that WF protein fractions and their peptide-enriched P and TC hydrolysates are excellent sources of multifunctional bioactives with antioxidant, antihyperglycemic and antihypertensive potential.

Antioxidant and Enzyme Inhibitory Activities of Rhoifolin Flavonoid: In Vitro and in Silico Studies.

Rhoifolin (apigenin-7-O-β-neohesperidoside) belongs to the class of flavonoids and was reported to exhibit anti-inflammatory, cytotoxic, antidiabetic, hepatoprotective, and cardioprotective activities. The current study presents the in-vitro evaluation of the antioxidative effects of rhoifolin by many assays, namely DPPH, CUPRAC, ABTS, phosphomolybdenum, and FRAP. Enzyme inhibitory potential was also evaluated for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, amylase, and glucosidase enzymes. While results revealed weak antioxidant activities for rhoifolin, the compound demonstrated some promising enzyme inhibitory effects against BChE (4.03 mg GALAE/g) and tyrosinase (7.44 mg KAE/g) but was not active on AChE. Regarding anti-diabetic enzymes, the compound was active on amylase but did not show any inhibition effect on glucosidase. In-silico molecular docking study was performed for rhoifolin on the active site of NADPH oxidase, BChE, and amylase enzymes to verify the observed enzyme inhibitory effect. Good binding affinities were observed for rhoifolin on all the docked enzymes, revealing numerous hydrogen bonds, carbon-hydrogen, van der Waals interactions. This is the first study to evaluate the enzyme inhibition potential of rhoifolin. We concluded that the increase in the degree of glycosylation might decrease the antioxidant abilities of flavonoids and that rhoifolin had moderate enzyme inhibition abilities to be investigated in future studies.

Antioxidant and Enzyme Inhibitory Potential of Streptomyces sp. G-18 Grown in Various Media.

Streptomyces are bacteria well known for producing bioactive secondary metabolites which are commonly found in diverse habitats. The biosynthesis of metabolites from Streptomyces is influenced by various factors such as the growth medium, environmental conditions, and gene regulation. This study aimed to investigate the influence of different growth media on biomass production and the antioxidant and enzyme inhibitory potential of a crude extract obtained from Streptomyces sp. G-18 isolated from high altitudinal soil of Nepal. The highest dry weight growth was observed in R2YE medium (184 mg/L), followed by R5 (144 mg/L), YEME (38 mg/L), and R5M media (30 mg/L). The crude extract showed notable antioxidant activities against free radicals. The highest alpha-amylase inhibition was observed in the R2YE medium, and worthy lipase and tyrosinase inhibition was observed in the YEME medium. However, only the R2YE medium exhibited inhibitory potential against elastase and acetylcholinesterase, while crude extracts from R5, YEME, and R5 modified did not show any such activity. Overall, our findings suggest that the production of bioactive secondary metabolites in Streptomyces sp. G-18 was significantly influenced by the growth medium. This strain may be a promising source of enzyme inhibitors with potential applications in the pharmaceutical and cosmetic industries.

Natural Anthraquinones as Promising MAPK3 Inhibitors for Complementary Cancer Therapy

Objective. MAPK3 activates several nuclear transcription factors, including c-Jun and c-fos, by phosphorylating its downstream cytoplasmic protein, thereby contributing to cell proliferation and survival. Different carcinomas’ initiation, progression, cancer cell metastasis, and drug resistance have been associated with MAPK3 overexpression. Given the need for new and potent MAPK3 inhibitors, this study aimed to explore the potential of anthraquinones (AQs) as organic compounds capable of inhibiting MAPK3. Methods. Using AutoDock 4.0 software, the binding affinity of 21 AQs to the receptor’s active site was evaluated. AQs were ranked based on their ΔGbinding values to the receptor’s active site, with the highest rankings receiving the most favorable scores. The Discovery Studio Visualizer tool was used to demonstrate the interaction modes between the highest-ranked AQs and the MAPK3 catalytic site. Furthermore, a 100-nanosecond molecular dynamics (MD) computer simulation was performed to assess the stability of the docked pose of the most potent enzyme inhibitor identified in this study. Results. The binding affinity of emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin to the receptor’s ATP binding cleft was noteworthy, as the ΔGbinding values were < − 10 kcal/mol. In addition, emodin-8-glucoside, aloe-emodin 8-glucoside, and pulmatin were found to have inhibition constant values at the picomolar concentration. According to our computer simulation results, the docked pose of emodin-8-glucoside within the active site of MAPK3 achieved a stable state after 70 ns. In other words, the root mean square deviation (RMSD) graph indicated stability within the 70–100 ns timeframe. Conclusion. Inhibition of MAPK3 by emodin-8-glucoside, aloe-emodin 8-glucoside, pulmatin, rhodoptilometrin, and hypericin may have therapeutic potential in cancer treatment.

Natural Products from Red Algal Genus Laurencia as Potential Inhibitors of RdRp and nsp15 Enzymes of SARS-CoV-2: An In Silico Perspective

The genus Laurencia, a category of marine red algae, is well recognized for producing a large variety of natural products (NPs) that are both chemically intriguing and structurally distinct. The aim of this research was to identify NPs with potential anti-SARS-CoV-2 activity. The crystals of the proteins RdRp and nsp15 were obtained from the RCSB protein database. About 300 NPs were discovered using the PubChem, ChemSpider, and CMNPD databases. The program Autodock Vina was used to conduct the molecular docking procedure once the proteins and ligands were prepared. Before running MD simulations using the CABS-flex 2.0 website, binding affinity assessments and interactions between amino acids were carefully reviewed. Only nine NPs were shortlisted to be examined further. Bromophycolide R, S, and bromophycoic acid C show the tendency to inhibit RdRp by β-hairpin motif binding at the N-terminal known as Active site 2 (AS2), whereas the other four NPs, bromophycolide E, H, P, and thyrsenol A, may effectively inhibit RdRp through interactions via C-terminal, also known as the Active site 1 (AS1). For the enzyme nsp15, bromophycoic B, C, and floridoside showed plausible interactions. In conclusion, out of nine, seven candidates shortlisted for RdRp exhibited strong interactions with the key residues in the AS1 and AS2 regions. Bromophycoic acid C may work as a dual inhibitor due to its favorable interactions with the nsp15 protein and RdRp’s N-terminal, with affinities of −8.5 and −8.2 kcal/mol, respectively.

Unveiling the phytochemical and pharmacological potential of Mimusops maxima (Poiret) Vaughan-an endemic plant with potential therapeutic effects

Mimusops maxima (Poiret) Vaughan is an endemic plant of Mauritius Island that has never been studied for neither its phytochemical nor pharmacological properties. Hence this study targeted to extract the phytochemicals using three different solvents and characterizion them through HPLC-MS-MS, alongside investigating their effects against chronic diseases. The methanolic extract beared the highest total phenolic and total flavonoid composition, (31.10 ± 0.25 gallic acid equivalents/gram (GAE/g) and 38.68 ± 0.34 rutin equivalent (mgRE/g)), respectively), succeeded by the ethyl acetate and aqueous extracts. The antioxidant assay demonstrated that the methanolic extract had the highest potency in terms of antioxidant potential. The most potent acetylcholinesterase enzyme inhibitor was the ethyl acetate extract (4.78 ± 0.28 mg GALAE/g) followed by the methanolic extract (4.48 ± 0.05 mgGALAE/g). The most inhibition of the tyrosinase enzyme was generated by the methanolic extract (122.53 ± 2.72 mg KAE/g),the ethyl acetate extract and aqueous extracts (113.96 ± 1.53 and 6.19 ± 0.30 mg KAE/g, respectively) followed and were behind the methanolic extract. The methanolic and ethyl acetate extracts can be formulated as tissanes and extracts as health supplements as a prophylaxis measure for non-communicable diseases pending further toxicological investigations.

Enterobacter hormaechei-Driven Novel Biosynthesis of Tin Oxide Nanoparticles and Evaluation of Their Anti-aging, Cytotoxic, and Enzyme Inhibition Potential.

Nanotechnology is a research hotspot that has gained considerable interest due to its potential inferences in the bioscience, medical, and engineering disciplines. The present study uses biomass from the Enterobacter hormaechei EAF63 strain to create bio-inspired metallic tin oxide nanoparticles (SnO2 NPs). The biosynthesized NPs were extensively analyzed using UV spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and Fourier transform infrared (FTIR) techniques. The identification of the crystalline phase was confirmed by XRD. The SEM technique elucidated the morphological characteristics and size of SnO2 NPs. SEM investigation revealed that the SnO2 NPs have a size of 10 nm with spherical morphology. The capping of NPs was confirmed by FTIR analysis that revealed the presence of different compounds found in the biomass of the E. hormaechei EAF63 strain. Later, EDX confirmed the elemental composition of NPs. Moreover, the synthesized SnO2 NPs were employed for important applications including anti-aging, anti-Alzheimer's, anti-inflammatory, anti-larvicidal, and antibacterial action against sinusitis pathogens. The highest value was observed for Streptococcus pyogenes (19.75 ± 0.46), followed by Moraxella catarrhalis (17.49 ± 0.82) and Haemophilus influenzae (15.31 ± 0.73), respectively. Among the used concentrations, the highest inhibition of 76.8 ± 0.93 for 15-lipoxygenase (15-LOX) was observed at 400 μg/mL, followed by 67.4 ± 0.91 for cyclooxygenase-1 (COX-1). So, as an outcome, E. hormaechei-mediated SnO2 NPs might be considered as the safe and effective nanoplatforms for multifunctional biological applications in the field of nanomedicine.