Inhibitory Potential Research Articles

The inhibitor activity of some azo compound derivatives using density functional theory and molecular dynamics simulations

Corrosion poses a significant challenge for metals and alloys, carrying considerable economic and safety consequences. Various manufacturing processes, including surface preparation techniques, further exacerbate it. While corrosion inhibitors are employed to safeguard these materials from corrosion, they can also induce oxidative damage. This study aims to determine the corrosion inhibition efficiency of the specified materials. Density Functional Theory (DFT) and molecular dynamics simulations (MDS) were used to investigate the electronic characteristics of diverse compounds. The study included key parameters including highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular orbital energy (ELUMO), energy gap (Eg) between ELUMO and EHOMO, dipole moment, global hardness, softness (σ), ionization energy (I), electron affinity (A), electronegativity (χ), back-donation energy Eb-d, global electrophilicity (ω), electron transfer, global nucleophilicity (ε), and total energy (sum of electronic and zero-point energies). The calculations were executed utilizing the DFT method, employing a 6-311G++(d,p) basis set at the B3LYP level. Our research aimed to rank materials based on their effectiveness in inhibiting corrosion by considering EHOMO, ELUMO, and Eg. The order of effectiveness was found to be as follows: S4 > S3 > S1 > Mad1 > Mad3 > Mad4 > P-azo > Bad4. Additionally, our Investigation delved into alterations in electron affinity (A) and ionization potential (I) within different solvent phases, highlighting their importance in determining the chemical reactivity and stability of the studied compounds. The reactive sites were selected using Fukui indices, and the molecular electrostatic potential (MESP) surface was characterized—a Monte Carlo simulation to further understand these chemicals' adsorption behavior on Fe (110) surfaces. Our findings revealed that these compounds exhibit corrosion inhibition potential due to their high EHOMO, A, σ, ΔN, ΔE-back-donation, and low Eg, ELUMO, I, and η. Moreover, our MESP surface analysis demonstrated their ability to donate electrons to the metal's d-orbitals and receive electrons through back-donation. The compounds investigated in this study exhibit the potential to be employed as corrosion inhibitors in various industrial sectors. As a result, through the use and determination of quantum computational chemistry parameters, the level of corrosion resistance was as follows S3 > S1 > Bad4 > Mad4 > Mad3 > S4 > Mad1 > P-azo.

INHIBISI ENZIM α-GLUKOSIDASE OLEH SENYAWA FLAVONOID DAUN KELOR (Moringa oleifera) IN SILICO DAN IN VITRO

Moringa leaves flavonoid have potential to inhibit α-glucosidase but they have low bioavailability, so they aremade in nanoparticles. It is also not known which specific flavonoid compounds from Moringa leaves have thepotential to inhibit α-glucosidase. This research aimed to determine the inhibition potential of α-glucosidase bythe moringa leaves flavonoid in silico through molecular docking and determine the inhibitory activity of α-glucosidase by moringa leaves flavonoid in extracts and nanoparticles in vitro. Moringa leaves flavonoid havepotential to be a competitive inhibiton of α-glucosidase with the highest to lowest inhibitory potential arecryptochlorogenic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin-3-glucoside, kaempferol-3-O-a-ramnoside, kaempferol-3-O-glucoside, epicathechins, catechins, quercetin, kaempferol, glucomoringinisothiocyanate. Cryptochlorogenic acid has the best potential with ΔG and Ki values -8.5 kcal/mol and 0.5788μM. Inhibition α-glucosidase moringa leaves flavonoid in extract and nanoparticles respectively are classified asinactive (IC 50 = 5.84x10 3 ppm) and active (IC 50 = 1.59x10 1 ppm) in vitro, so nanoparticles can increase theinhibitory activity.

Chemo-profiling and exploring therapeutic potential of Momordica dioica Roxb. ex Willd. for managing metabolic related disorders: In-vitro studies, and docking based approach

Ethnopharmacological relevanceMomordica dioica Roxb. ex Willd. (M. dioica Roxb.) a nutritious and therapeutic property rich crop of Cucurbitaceae plant family. In various folklore medicine including Ayurveda fruits are used to treat several metabolic related disorders i.e., hyperglycemia, hyperlipidemia, diabetes, obesity etc. Furthermore, traditionally it is used to treat fever, inflammation, ulcer, skin diseases, haemorrhoids, hypertension and also employed as cardioprotective, hepatoprotective, analgesic, diuretic. Aim of the studyThis study focuses to explore the therapeutic potential of Momordica dioica Roxb. ex Willd. through in-vitro and in-silico approach for managing hyperlipidemia, hyperglycemia and related metabolic disorders along with its phytochemical profiling for quality evaluation and validation of traditional claim. Materials and methodsThe present study was carried out on hydroalcohol extract of dried leaf and fruit of Momordica dioica. In-vitro antioxidant potential using DPPH and Nitric oxide scavenging assay along with in-vitro enzyme inhibitory potential against α-amylase, α-glucosidase, and pancreatic lipase enzymes was studied. The bioactive metabolites were identified from the most potent bioactive extract by analysis with LC-QTOF-MS and also studied their role to lessen the metabolic related disorder through in-silico approaches. ResultsThe results confirmed that the fruit extract is more active to possess antioxidant and prominent enzyme inhibition potential compared to the leaf. Sixteen identified metabolites in M. dioica Roxb. fruits may be responsible for the therapeutic potential related to metabolic related disorder. The in-silico study of the identified phytomolecules against α-amylase, α-glucosidase and pancreatic lipase showed significant docking scores ranging from −9.8 to −5.5, −8.3 to −4.8 and −8.3 to −6 respectively. ConclusionThe current study illustrated that M. dioica Roxb., a traditionally important plant is potential against metabolic related disorders. Phytocomponents present in the fruit extract may be responsible for antioxidant as well as the enzymes’ inhibitory potential. Thus, fruits of M. dioica Roxb. will be useful as alternative therapeutics for treatment of hyperlipidemia, hyperglycemia and related metabolic disorders.

Synergistic integration of deep learning with protein docking in cardiovascular disease treatment strategies.

This research delves into the exploration of the potential of tocopherol-based nanoemulsion as a therapeutic agent for cardiovascular diseases (CVD) through an in-depth molecular docking analysis. The study focuses on elucidating the molecular interactions between tocopherol and seven key proteins (1O8a, 4YAY, 4DLI, 1HW9, 2YCW, 1BO9 and 1CX2) that play pivotal roles in CVD development. Through rigorous in silico docking investigations, assessment was conducted on the binding affinities, inhibitory potentials and interaction patterns of tocopherol with these target proteins. The findings revealed significant interactions, particularly with 4YAY, displaying a robust binding energy of -6.39 kcal/mol and a promising Ki value of 20.84 μM. Notable interactions were also observed with 1HW9, 4DLI, 2YCW and 1CX2, further indicating tocopherol's potential therapeutic relevance. In contrast, no interaction was observed with 1BO9. Furthermore, an examination of the common residues of 4YAY bound to tocopherol was carried out, highlighting key intermolecular hydrophobic bonds that contribute to the interaction's stability. Tocopherol complies with pharmacokinetics (Lipinski's and Veber's) rules for oral bioavailability and proves safety non-toxic and non-carcinogenic. Thus, deep learning-based protein language models ESM1-b and ProtT5 were leveraged for input encodings to predict interaction sites between the 4YAY protein and tocopherol. Hence, highly accurate predictions of these critical protein-ligand interactions were achieved. This study not only advances theunderstanding of these interactions but also highlights deep learning's immense potential in molecular biology and drug discovery. It underscores tocopherol's promise as a cardiovascular disease management candidate, shedding light on its molecular interactions and compatibility with biomolecule-like characteristics.

Designing JAK2 Inhibitors Beyond Myeloproliferative Neoplasms ‐ Theoretical and Experimental Analysis for Solid Cancers

AbstractSomatic mutations in JAK2 have been reported to cause myeloproliferative neoplasms, autoimmune disorders, rheumatoid arthritis, and inflammation. JAK2 protein with PDB id 3FUP was selected for docking analysis via cross‐docking. Molecular docking of JAK2 with ATP and crystal ligand revealed their binding affinities and interactions. 3D QSAR models with R2=0.997 and Q2=0.984 having high stability and predictivity were generated. The biological activity of the hit compound obtained from virtual screening, LAS 26879206, was predicted to be 4.21 using the 3D QSAR model. Modification of LAS 26879206 utilizing 3D QSAR contours for modulating its JAK2 inhibitory potential yielded two novel inhibitors with a 2‐aminopyrimidine core – ACP1 and ACPM1. Molecular docking, molecular dynamics simulations, and ADMET analysis indicated improvements in the efficiency of these compounds compared to the hit compound. Synthesis of these compounds was carried out using a two‐step reaction‐ first Buchwald – Hartwig coupling reaction to yield an intermediate ACB1 which was then coupled with appropriate boronic acids via Suzuki reaction to get ACP1 and ACPM1. The effects of these designed compounds as anticancer agents were analyzed in hCT‐116 (human colorectal carcinoma), HeLa (cervical carcinoma), A549 (human lung adenocarcinoma), and A375 (human melanoma) cell lines. ACPM1 was found to be active in all the cell lines with a pIC50 of 5 which was in concordance with the in silico studies. Western blot analysis validated the JAK2 inhibitory property of ACPM1 which can be further ensured by in vivo studies.

Phytochemical, antimicrobial and proximate analysis of <em>Costus spectabilis</em> grown in different soil types

The search for medicinal plants with novel properties for therapeutical potentials is a continuum. The preliminary phytochemical analysis, antimicrobial properties and proximate contents of Costus spectabilis leaf and root harvested from different soil types were studied following standard protocols. The ethyl ethanoate extracts were assayed against six microbial cultures of Staphylococcus aureus (ATCC 29523), Pseudomonas aeruginosa (ATCC 27853), Bacillus subtilis (ATCC 6633), Aspergillus niger, Candida albicans, and Aspergillus clavatus using the agar well diffusion methods. The phytochemical analysis revealed the presence of alkaloids, saponin, phenol, flavonoids and anthraquinone in all samples at varying concentrations. Terpenes and phlobatannins were not observed in any extract. Phenolic compound was observed to have the highest quantity of 6.18±0.00 mg/g from the leaf extract of the plant grown in loamy soil. Tannin and flavonoids were only detected in very insignificant quantities. The extracts showed significant inhibitory potential against the bacterial strains. The highest zone of inhibition was recorded as 33.02±1.45 mm against B. subtilis in the leaf extracts of the plant grown in clay soil. The leaf extracts from the plant obtained from clay soil showed fungicidal activity against the Aspergillus species, while the other extracts only showed fungistatic effects against all sampled fungal species. The proximate content analysis revealed that carbohydrates and protein are the dominant nutrients in the leaf of C. spectabilis. Costus spectabilis is a plant that can be exploited for its medicinal, nutritional and economic values.

Anti-diabetic, anti-pancreatic lipase, and anti-protein glycation potential of Irvingia gabonensis stem bark extracts: in vitro and in silico studies.

Diabetes mellitus is a chronic metabolic disorder that affects glucose, lipid, and protein metabolism. Targeting these metabolic derangements can optimize the therapeutic strategies for this disease. Utilizing in vitro and in silico models, this study investigated the ability of aqueous and ethanol extracts of Irvingia gabonensis to inhibit α-amylase, α-glucosidase, pancreatic lipase, and protein glycation. High-performance liquid chromatography (HPLC) was used to identify the compounds found in the stem bark of I. gabonensis. In silico analysis determined the binding mode and mechanism of interactions between the enzymes and phytochemicals. With an IC50 value of 11.47µg/ml, the aqueous extract demonstrated higher inhibitory efficacy against α-amylase compared to the ethanol extract (IC50 19.88µg/ml). However, the ethanol extract had stronger inhibitory activities against α-glucosidase, pancreatic lipase, and protein glycation compared to the aqueous extract (IC50 values of 3.05, 32.85, 0.0014 versus 25.72, 332.42, 0.018µg/ml respectively). Quercetin ranked highest in binding energy with α-amylase (-6.6kcal/mol), α-glucosidase (-6.6kcal/mol), and pancreatic lipase (-5.6kcal/mol). This was followed by rhamnetin (6.5, 6.5, and 6.1kcal/mol respectively). Hydrogen bonding, hydrophobic interactions, and pi-pi stacking are forces responsible for the binding of quercetin and rhamnetin to these enzymes. Molecular dynamics simulation showed that the lead phytochemicals formed stable and energetically stabilized complexes with the target proteins. This study showed that the extracts of I. gabonensis stem bark had significant in vitro anti-diabetic, anti-pancreatic lipase, and anti-protein glycation activities. The strong binding affinities of some of the identified compounds could be responsible for the inhibitory potential of the extracts. I. gabonensis stem bark could be further explored as a natural remedy for the treatment of diabetes mellitus and its complications.

Exploring peptidomes of by-products generated during chhurpi production using Lactobacillus delbrueckii WS4 for identification of novel bioactive peptides.

The considerable value of whey is evident from its significant potential applications and contributions to the functional food and nutraceutical market. The by-products were individually obtained during functional chhurpi and novel soy chhurpi cheese production using defined lactic acid bacterial strains of Sikkim Himalaya's traditional chhurpi. Hydrolysis of substrate proteins by starter proteinases resulted in a comparable peptide content in whey and soy whey which was associated with antioxidant and ACE inhibition potential. Peptidome analysis of Lactobacillus delbrueckii WS4 whey and soy whey revealed the presence of several bioactive peptides including the multifunctional peptides PVVVPPFLQPE and YQEPVLGPVRGPFPIIV. In silico analyses predicted the antihypertensive potential of whey and soy whey peptides with strong binding affinity for ACE active sites. QSAR models predicted the highest ACE inhibition potential (IC50) for the β-casein-derived decapeptide PVRGPFPIIV (0.95 μM) and the Kunitz trypsin inhibitor protein-derived nonapeptide KNKPLVVQF (16.64 μM). Chhurpi whey and soy whey can be explored as a valuable source of diverse and novel bioactive peptides for applications in designer functional foods development.

Exploring optimal drug targets through subtractive proteomics analysis and pangenomic insights for tailored drug design in tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis, ranks among the top causes of global human mortality, as reported by the World Health Organization’s 2022 TB report. The prevalence of M. tuberculosis strains that are multiple and extensive-drug resistant represents a significant barrier to TB eradication. Fortunately, having many completely sequenced M. tuberculosis genomes available has made it possible to investigate the species pangenome, conduct a pan-phylogenetic investigation, and find potential new drug targets. The 442 complete genome dataset was used to estimate the pangenome of M. tuberculosis. This study involved phylogenomic classification and in-depth analyses. Sequential filters were applied to the conserved core genome containing 2754 proteins. These filters assessed non-human homology, virulence, essentiality, physiochemical properties, and pathway analysis. Through these intensive filtering approaches, promising broad-spectrum therapeutic targets were identified. These targets were docked with FDA-approved compounds readily available on the ZINC database. Selected highly ranked ligands with inhibitory potential include dihydroergotamine and abiraterone acetate. The effectiveness of the ligands has been supported by molecular dynamics simulation of the ligand–protein complexes, instilling optimism that the identified lead compounds may serve as a robust basis for the development of safe and efficient drugs for TB treatment, subject to further lead optimization and subsequent experimental validation.

Enrichment and Quantitation of Dipeptidyl Peptidase IV Inhibitory Peptides in Quinoa upon Systematic Malting.

Food-derived peptides with an inhibitory effect on dipeptidyl peptidase IV (DPP-IV) can be used as an additive treatment for type 2 diabetes. The inhibitory potential of food depends on technological protein hydrolysis and gastrointestinal digestion, as the peptides only act after intestinal resorption. The effect of malting as a hydrolytic step on the availability of these peptides in grains has yet to be investigated. In this study, quinoa was malted under systematic temperature, moisture, and time variations. In the resulting malts, the DPP-IV inhibition reached a maximum of 45.02 (±10.28) %, whereas the highest overall concentration of literature-known inhibitory peptides was 4.07 μmol/L, depending on the malting parameters. After in vitro gastrointestinal digest, the inhibition of most malts, as well as the overall concentration of inhibitory peptides, could be increased significantly. Additionally, the digested malts showed higher values in both the inhibition and the peptide concentration than the unmalted quinoa. Concerning the malting parameters, germination time had the highest impact on the inhibition and the peptide concentration after digest. An analysis of the protein sizes before and after malting gave first hints toward the origin of these peptides, or their precursors, in quinoa.

Anti-black pod disease activity of leaf extract of Carica papaya Linn

BackgroundTheobroma cacao (Cocoa) is a major foreign exchange earner for Ghana. Over the recent decades, there has been a consistent decline in cocoa production in the country. A major contributing factor is the cocoa black pod disease caused by Phytophthora species. Synthetic fungicides have been used to control the pathogens over the years. However, recent calls for organic cocoa devoid of residues from synthetic fungicides, which are known to pose several health challenges as well as a negative impact on the environment, have gained attention. Thus, inviting investigations into more environmentally friendly and sustainable alternatives to synthetic fungicides. ObjectiveThis study explored the inhibitory potential of crude extract from Carica papaya against cocoa black pod disease caused by Phytophthora spp. Material and methodsAn in-silico study was done using known phytochemicals from Carica papaya as ligands against a Phytophthora effector protein. Crude extracts were obtained from the plant materials using 70 % ethanol as the extraction solvent. The crude Green Leaf Extract (GLE), Aging Induced Chlorophyll Deficient Leaf Extract (AICDLE), and Matured Black Seed Extract (SDE) were tested in-vitro against pre-cultured P. palmivora and P. megakarya using the poison food technique. GLE was modulated with Delco, a synthetic fungicide, at different ratios which were tested in-vitro and in-vivo. ResultsA total of 16 ligands showed binding affinity higher or equal to the standard ligand, alliin, suggesting Carica papaya as a repository of anti-phytophthora agents. Assessment of crude extracts at concentrations 5–20 mg/ml showed fungistatic activity against P. palmivora and P. megakarya in-vitro. Modulation of GLE with Delco produced some combinations that made GLE fungicidal in-vitro against P. palmivora and P. megakarya with fractional inhibition concentration indices between 0.51 and 0.65, interpreted as partially synergistic. The in-vivo assessment of combination D (Delco and GLE in a 0.3 mg:3 mg per ml ratio) performed as well as Delco alone at the recommended dose of 5 mg/ml. Thus, combination D reduces the requirement for copper-based fungicide by over 90 %. ConclusionThis study shows Carica papaya in a new light as a potential material that could be formulated into a natural product-based fungicide for combating Phytophthora-induced black pod disease.

Exploring the Biofilm Inhibition Potential of a Novel Phytic Acid-Crosslinked Chitosan Nanoparticle: In Vitro and In Vivo Investigations.

The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.

COAGULATION AND ANTICOAGULATION PARAMETERS IN MULTIPLE SCLEROSIS PATIENTS WITH AND WITHOUT COVID-19

The aim. To investigate plasma levels of main coagulation and fibrinolytic factors in MS patients with and without COVID-19 history. Materials and methods. A total of 127 participants were enrolled in this study, including 97 MS patients and 30 healthy controls (HC). Patients with MS were divided into two groups: MS+Covid group (n=41) – patients with MS, who had a laboratory-verified diagnosis of COVID-19 in the past 3-6-month period and MS group (n=56) – patients with MS, who did not suffer from COVID-19 previously. Determination of plasma levels of prothrombin, plasminogen, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), protein C (PC), soluble thrombomodulin (TM) was performed by means of enzyme-linked immunosorbent assay. Spectrophotometric techniques were used to determine concentrations of fibrinogen, soluble fibrin monomeric complexes (SFMC) as well as plasminogen activity and inhibitory potential of α-2-antiplasmin. Results. The MS group was characterized by elevated levels of plasma prothrombin, fibrinogen, D-dimer, SFMC, soluble TM compared to HC, while PC concentration did not differ between MS and HC groups. Plasma plasminogen level as well as plasma level of the potential plasmin activity were significantly decreased in MS patients compared to HC group. The plasma tPA level was significantly reduced while plasma PAI-I level was significantly increased in MS patients compared to HC. Patients of MS group had an increased level of plasma α-2-antiplasmin activity compared with HC group. To note, most of studied parameters did not differ between two MS groups, except protein C, soluble thrombomodulin levels and plasma α-2-antiplasmin activity. Conclusions. The results of our study showed that MS patients have got altered hemostasis parameters; however, further study is necessary to find out the relationship between particular components of coagulation and fibrinolytic systems and pathophysiology of MS. Additionally, our findings demonstrated that a SARS-CoV-2 infection had a limited effect on hemostasis parameters in MS patients, causing changes in only a few parameters, including thrombomodulin and protein C levels as well as α-2-antiplasmin activity.

Chemical Composition and In Vitro and In Silico Biological Activities of Myrciaria tenella (DC.) O.Berg (Myrtaceae) Essential Oil from Brazil

Myrciariatenella O.Berg, a native plant species of Brazil, exhibits pharmacological applications, including antitumor activity. In this study, we isolated the essential oil (EO) of M. tenella and identified its phytochemical profile. In addition, we determined the in vitro and in silico cytotoxic activities of EO in nontumor and tumor cell lines (gingival fibroblasts and oral squamous cell carcinoma, respectively) and its free radical scavenging activity (i.e., antioxidant activity) using ABTS and DPPH assays. The EO of M. tenella primarily constitutes hydrocarbons and oxygenated sesquiterpenes, with (E)-caryophyllene (33.95%), δ-cadinene (7.4%), caryophyllene oxide (4.74%), and viridiflorene (4.49%) as its four major components. EO effectively suppressed the cell viability of CAL-27 tumor cells to below 70% at concentrations of 125 and 250 μg/mL and exhibited a free radical inhibition potential of 75.63 ± 0.41% and 28.46 ± 0.36%, respectively, in the DPPH and ABTS assays. This chemical and biological potential may be attributed to the major compounds present in EO, as well as the molecular coupling simulations conducted, which revealed the anticancer mechanism of EO in the sesquiterpenes (E)-caryophyllene, δ-cadinene, caryophyllene oxide, and viridiflorene.

A multidimensional study for design functional foods: Chemical profiling, antioxidant potential, enzyme inhibition, and cytotoxic effects of Alkanna tubulosa extracts

This study focuses on the extraction of plant species Alkanna tubulosa growing in Turkey, using solvents of different polarities (ethyl acetate, ethanol, ethanol/water, and water) and determining their chemical composition and biological activity. The extracts were subjected to qualitative LC-MS/MS analyses, which resulted in the identification of even 50 different secondary metabolites in some extracts. The existence of total phenols and flavonoids was determined. of total phenols and flavonoids was determined. The antioxidant capacity was evaluated by various in vitro assays, as well as the enzyme inhibitory capacity against cholinesterases (AChE and BChE), tyrosinase, α-amylase, and α-glucosidase, as well as human isoforms of carbonic anhydrase. In addition, the cytotoxic activity of the extracts was also examined. The results showed that the ethanol/water extract showed the strongest antioxidant activity (225.55 mg TE/g extract in ABTS and 381.14 mg TE/g extract in CUPRAC), probably due to the high total phenol (105.17 mg GAE/g extract) and flavonoids (20.12 mg RE/g extract) content, while the ethanol extract showed the strongest enzyme inhibitory potential. These chemical and biological findings provide valuable insights for potential future products based on the A. tubulosa extracts which could be used in various industries.

A comparative study between nanostructured lipid carriers and invasomes for the topical delivery of luteolin: Design, optimization and pre-clinical investigations for psoriasis treatment

Psoriasis is an inflammatory skin condition manifested by hyper-proliferation and reactive aberrant epidermal differentiation, in which genetic and environmental factors have a significant role. The current context is focused on designing novel nanovesicular systems (invasomes) incorporating terpenes with reported anti-inflammatory potential and loaded with a nutraceutical compound (luteolin/Lut) for treatment of psoriasis. Additionally, their topical efficacy in psoriasis treatment compared to lipid-based nanocarriers (nanostructured lipid carriers) was investigated. Invasomes were assessed regarding their particle size (PS), zeta potential (ζ-potential), drug entrapment (EE%), storage stability, in-vitro drug release profile and release kinetics. The optimized vesicles were investigated for their ex-vivo skin deposition and in-vitro anti-inflammatory potential in comparison with nanostructured lipid carriers (NLCs). The optimized formulation was selected to carry out the in-vivo study using rat model of imiquimod-induced psoriasis. Luteolin-invasomes were found to have spherical shape and promising colloidal properties. They possessed PS ranging from 277.80 to 812.91 nm, negative ζ-potential (−35.22–38.55 mV), and high EE% values, which ranged from 89.38 to 99.75 %. Furthermore, they exhibited good stability properties and significant sustainment of drug release in comparison to NLCs. In addition, they were able to enhance Lut deposition by 2.1-fold in the stratum corneum (SC) and 5.5-fold in epidermis and dermis compared to control suspension of Lut. Moreover, invasomes showed more potential to retain Lut into deep skin layers 1.5-fold higher than NLCs. They also displayed higher in-vitro anti-inflammatory activity compared to plain invasomes and control suspension, and comparable activity compared to NLCs. In the in-vivo animal study, the ability of Lut to alleviate psoriatic symptoms was significantly enhanced after its encapsulation in invasomal dispersions, where Lut-invasomes possessed a great inhibitory potential compared to the control Lut suspension, and even to Lut-NLCs. This suggests their efficiency in treating psoriasis, delineating them promising for further use in treating other inflammatory skin conditions.

Synthesis and in silico inhibitory action studies of azo-anchored imidazo[4,5-b]indole scaffolds against the COVID-19 main protease (Mpro)

The present work elicits a novel approach to combating COVID-19 by synthesizing a series of azo-anchored 3,4-dihydroimidazo[4,5-b]indole derivatives. The envisaged methodology involves the l-proline-catalyzed condensation of para-amino-functionalized azo benzene, indoline-2,3-dione, and ammonium acetate precursors with pertinent aryl aldehyde derivatives under ultrasonic conditions. The structures of synthesized compounds were corroborated through FT-IR, 1H NMR, 13C NMR, and mass analysis data. Molecular docking studies assessed the inhibitory potential of these compounds against the main protease (Mpro) of SARS-CoV-2. Remarkably, in silico investigations revealed significant inhibitory action surpassing standard drugs such as Remdesivir, Paxlovid, Molnupiravir, Chloroquine, Hydroxychloroquine (HCQ), and (N3), an irreversible Michael acceptor inhibitor. Furthermore, the highly active compound was also screened for cytotoxicity activity against HEK-293 cells and exhibited minimal toxicity across a range of concentrations, affirming its favorable safety profile and potential suitability. The pharmacokinetic properties (ADME) of the synthesized compounds have also been deliberated. This study paves the way for in vitro and in vivo testing of these scaffolds in the ongoing battle against SARS-CoV-2.

Piperine Enhances Antimalarial Activity of Methyl Gallate and Palmatine Combination.

Artemisinin combination therapies, the first-line antimalarials in Nigeria, have reportedly suffered multiple failures in malaria treatment, hence the search for novel combination of other compounds. Methyl gallate and palmatine have been reported to exhibit antiplasmodial activities but the antimalarial activity of their combination has not been evaluated. Therefore, the evaluation of the combination of methyl gallate and palmatine for antimalarial activity in vitro and in vivo in the presence of piperine was carried out. The inhibitory potential of methyl gallate and palmatine combination on β-hematin (hemozoin) formation was studied in vitro. Also, the antimalarial activity of methyl gallate and palmatine combination with/without a bioenhancer (piperine) was evaluated in Plasmodium berghei NK65-infected mice. Methyl gallate and palmatine in the ratio 3:2 acted synergistically in vitro and had the highest inhibitory effect (IC50 = 0.73µg/mL) on β-hematin (hemozoin) formation. The 3:2 combination of methyl gallate and palmatine exhibited no antimalarial activity in vivo in the absence of piperine but caused reduction in parasitemia that exceeded 40% in the presence of piperine at the dose of 25mg/kg body weight on days 6 and 8 post-inoculation in mice. The 3:2 combination of methyl gallate and palmatine in the presence of piperine exhibited antimalarial activity in vivo, possibly by synergistic inhibition of hemozoin formation which may cause accumulation of haem within the food vacuole of Plasmodium spp. and its death.

Chemoinformatic study on phytochemicals from Melissa officinalis for ligand based drug design inhibition of aflatoxins synthesis

This study involved extracting 2D structures of fifty-one (51) GC-MS chromatogram-generated compounds from PubChem a free depository database for generating a library of compounds and obtaining the 3D structure of polyketide synthase A, an enzyme recognized for the biosynthesis of aflatoxin in Aspergillus species, from the protein data bank. In silico (molecular docking was performed to assess the interactions of the phytochemicals in the sample and were screened for their inhibitory potential, having higher binding energy, and favorable pharmacokinetics profiles. The docking analysis outcome indicates that nine (9) compounds exhibited binding energies ranging from −11.314 to −8.365 kcal/mol which is higher than the control (PLM) with a binding energy of −8.131 kcal/mol. It is observed that many of the compounds interacted with the target using hydrophobic interaction and only a few added hydrogen bonds and salt bridges. This research has shown a potential of the aerial part of Melissa officinalis vegetable for drug development to inhibit the synthesis of aflatoxins from Aspergillus flavus. The study has showcased good scientific information for the development of natural products for the prevention and treatment of aflatoxin contamination in agricultural products.

Bioassay-Guided and DeepSAT-Driven Precise Mining of Monoterpenoid Coumarin Derivatives with Antifeedant Effects from the Leaves of Ailanthus altissima.

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.