iDVEIP: A computer-aided approach for the prediction of viral entry inhibitory peptides.

With the notable surge in therapeutic peptide development, various peptides have emerged as potential agents against virus-induced diseases. Viral entry inhibitory peptides (VEIPs), a subset of antiviral peptides (AVPs), offer a promising avenue as entry inhibitors (EIs) with distinct advantages over chemical counterparts. Despite this, a comprehensive analytical platform for characterizing these peptides and their effectiveness in blocking viral entry remains lacking. In this study, we introduce a groundbreaking in silico approach that leverages bioinformatics analysis and machine learning to characterize and identify novel VEIPs. Cross-validation results demonstrate the efficacy of a model combining sequence-based features in predicting VEIPs with high accuracy, validated through independent testing. Additionally, an EI type model has been developed to distinguish peptides specifically acting as Eis from AVPs with alternative activities. Notably, we present iDVEIP, a web-based tool accessible at http://mer.hc.mmh.org.tw/iDVEIP/, designed for automatic analysis and prediction of VEIPs. Emphasizing its capabilities, the tool facilitates comprehensive analyses of peptide characteristics, providing detailed amino acid composition data for each prediction. Furthermore, we showcase the tool's utility in identifying EIs against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Mosaic HIV-1 vaccination induces anti-viral CD8+ T cell functionality in the phase 1/2a clinical trial APPROACH.

IMPORTANCE: The functionality of CD8+ T cells against human immunodeficiency virus-1 (HIV-1) antigens is indicative of HIV-progression in both animal models and people living with HIV. It is, therefore, of interest to assess CD8+ T cell responses in a prophylactic vaccination setting, as this may be an important component of the immune system that inhibits HIV-1 replication. T cell responses induced by the adenovirus serotype 26 (Ad26) mosaic vaccine regimen were assessed previously by IFN-γ ELISpot and flow cytometric assays, yet these assays only measure cytokine production but not the capacity of CD8+ T cells to inhibit replication of HIV-1. In this study, we demonstrate direct anti-viral function of the clinical Ad26 mosaic vaccine regimen through ex vivo inhibition of replication of diverse clades of HIV-1 isolates in the participant's own CD4+ T cells.

iDVIP: identification and characterization of viral integrase inhibitory peptides.

Antiretroviral peptides are a kind of bioactive peptides that present inhibitory activity against retroviruses through various mechanisms. Among them, viral integrase inhibitory peptides (VINIPs) are a class of antiretroviral peptides that have the ability to block the action of integrase proteins, which is essential for retroviral replication. As the number of experimentally verified bioactive peptides has increased significantly, the lack of in silico machine learning approaches can effectively predict the peptides with the integrase inhibitory activity. Here, we have developed the first prediction model for identifying the novel VINIPs using the sequence characteristics, and the hybrid feature set was considered to improve the predictive ability. The performance was evaluated by 5-fold cross-validation based on the training dataset, and the result indicates the proposed model is capable of predicting the VINIPs, with a sensitivity of 85.82%, a specificity of 88.81%, an accuracy of 88.37%, a balanced accuracy of 87.32% and a Matthews correlation coefficient value of 0.64. Most importantly, the model also consistently provides effective performance in independent testing. To sum up, we propose the first computational approach for identifying and characterizing the VINIPs, which can be considered novel antiretroviral therapy agents. Ultimately, to facilitate further research and development, iDVIP, an automatic computational tool that predicts the VINIPs has been developed, which is now freely available at http://mer.hc.mmh.org.tw/iDVIP/.

AChE inhibitory activity of N-substituted natural galanthamine derivatives.

Galanthamine derivatives are known for their AChE inhibitory activity. Among them, galanthamine has been approved for treatment of Alzheimer's disease. N-Acetylnorgalanthamine (narcisine) and N-(2'-methyl)allylnorgalanthamine (the most potent natural AChE inhibitor of galanthamine type) were synthetized using N-norgalanthamine as a precursor. The NMR data described previously for narcisine were revised by two-dimensional 1H-1H and 1H-13C chemical shift correlation experiments. AChE inhibitory assays showed that N-acetylnorgalanthamine and N-formylnorgalanthamine (with previously unknown activity) are 4- and 43-times, respectively, less potent than galanthamine. In vitro (AChE inhibitory) and in silico (docking, ADME) assays and comparison of N-(2'-methyl)allylnorgalanthamine with galanthamine prove that this molecule is a very promising natural AChE inhibitor (33-times more potent than galanthamine) which further in vivo studies would provide better estimation about its applicability as a drug.

Rational design, synthesis and biological evaluation of novel HIV-1 protease inhibitors containing 2-phenylacetamide derivatives as P2 ligands with potent activity against DRV-Resistant HIV-1 variants.

A novel kind of potent HIV-1 protease inhibitors, containing diverse hydroxyphenylacetic acids as the P2-ligands and 4-substituted phenyl sulfonamides as the P2' ligands, were designed, synthesized and evaluated in this work. Majority of the target compounds exhibited good to excellent activity against HIV-1 protease with IC50 values below 200 nM. In particular, compound 18d with a 2-(3,4-dihydroxyphenyl) acetamide as the P2 ligand and a 4- methoxybenzene sulfonamide P2' ligand exhibited inhibitory activity IC50 value of 0.54 nM, which was better than that of the positive control darunavir (DRV). More importantly, no significant decline of the potency against HIV-1DRVRS (DRV-resistant mutation) and HIV-1NL4_3 variant (wild type) for 18d was detected. The molecular docking study of 18d with HIV-1 protease (PDB-ID: 1T3R, www.rcsb.org) revealed possible binding mode with the HIV-1 protease. These results suggested the validity of introducing phenol-derived moieties into the P2 ligand and deserve further optimization which was of great value for future discovery of novel HIV-1 protease.

Bacterial recognition and inhibition activities of an LRR-only protein in the Chinese mitten crab, Eriocheir sinensis.

LRR-only protein (LRRop) is an important class of immune molecules that function as pattern recognition receptor in invertebrates, however, the bacterial inhibitory activity of this proteins remain largely unknown. Herein, a novel LRRop was cloned from Eriocheir sinensis and named as EsLRRop2. The EsLRRop2 consists of six LRR motifs and formed a horseshoe shape three-dimension structure. EsLRRop2 was mainly expressed in intestine and hepatopancreas. The transcripts of EsLRRop2 in the intestine and hepatopancreas were induced by Vibrio parahaemolyticus and Staphylococcus aureus, and displayed similar transcriptional profiles. The expression levels of EsLRRop2 responded more rapidly and highly to V. parahaemolyticus than S. aureus in the intestine and hepatopancreas. Although the basal expression level of EsLRRop2 in hemocytes was relatively low, its transcripts in hemocytes were significantly induced by V. parahaemolyticus and S. aureus. The recombinant proteins of EsLRRop2 (rEsLRRop2) displayed a wide range of binding spectrum against vibrios, including V. parahaemolyticus, V. alginolyticus, and V. harveryi. The rEsLRRop2 showed dose- and time-dependent inhibitory activity against V. parahaemolyticus and S. aureus, and it could agglutinate the two bacteria. Furthermore, the inhibitory activities of rEsLRRop2 against V. parahaemolyticus, V. alginolyticus, V. harveryi and S. aureus was slightly affected by pH and salinity, and the rEsLRRop2 displayed the strongest inhibitory activity against all the three vibrios when the salinity was 20 ‰ and pH was 8.0. Collectively, these results elucidate the bacterial binding and inhibitory activities of EsLRRop2, and provide theoretical foundations for the application of rEsLRRop2 in prevention and control of vibrio diseases in aquaculture.

Expression characteristics and inhibitory activity of a leucine-rich repeat (LRR)-only protein in the Chinese mitten crab, Eriocheir sinensis.

The leucine-rich repeat (LRR) domain is a crucial structure in a variety of immune related proteins and displays multiple immune functions. In this study, the open reading frame (ORF) of an LRR-only protein was cloned from the Chinese mitten crab, Eriocheir sinensis (EsLRRop1). The protein sequence of EsLRRop1 contained seven LRR motifs, three LRR-TYP motifs and an LRRCT motif. Tissue distribution exhibited that EsLRRop1 mainly expressed in nervous tissues including thoracic ganglion, eyestalk and brain while showed relatively lower transcriptional level in hemocyte. Based on the above expression characteristics, the responses of EsLRRop1 to the challenge of Vibrio parahaemolyticus and Staphylococcus aureus were tested. The result showed that the transcript of EsLRRop1 in thoracic ganglion and eyestalk up-regulated after being challenged with S. aureus, while it decreased post injection with V. parahaemolyticus. The transcript of EsLRRop1 in hemocytes up-regulated sharply at 3 h and decreased at 12 h and 24 h after being challenged with V. parahaemolyticus, while it decreased at 12 h and 24 h post injection with S. aureus. The recombinant protein of EsLRRop1 (His-EsLRRop1) displayed binding activities to V. alginolyticus, V. harveyi, V. parahaemolyticus, S. aureus, Corynebacterium glutamicum and Micrococcus lysodeikticus as well as lipopolysaccharide (LPS) and peptidoglycan (PGN). Moreover, the His-EsLRRop1 exhibited inhibitory activity against V. parahaemolyticus and V. harveyi with minimum inhibitory concentration (MIC) of 3.57-7.14 µM and 7.14-14.28 µM, respectively. These results provide theoretical basis for the application of EsLRRop1 in inhibiting bacteria in aquaculture practice.

An insight into the mechanistic role of (-)-Ampelopsin F from Vatica chinensis L. in inducing insulin secretion in pancreatic beta cells.

Resveratrol oligomers, ranging from dimers to octamers, are formed through regioselective synthesis involving the phenoxy radical coupling of resveratrol building blocks, exhibiting remarkable therapeutic potential, including antidiabetic properties. In this study, we elucidate the mechanistic insights into the insulin secretion potential of a resveratrol dimer, (-)-Ampelopsin F (AmF), isolated from the acetone extract of Vatica chinensis L. stem bark in Pancreatic Beta-TC-6 cell lines. The AmF (50 µM) treated cells exhibited a 3.5-fold increase in insulin secretion potential as compared to unstimulated cells, which was achieved through the enhancement of mitochondrial membrane hyperpolarization, elevation of intracellular calcium concentration, and upregulation of GLUT2 and glucokinase expression in pancreatic Beta-TC-6 cell lines. Furthermore, AmF effectively inhibited the activity of DPP4, showcasing a 2.5-fold decrease compared to the control and a significant 6.5-fold reduction compared to the positive control. These findings emphasize AmF as a potential lead for the management of diabetes mellitus and point to its possible application in the next therapeutic initiatives.

Alstomaphylines A-K, monoterpenoid bisindole alkaloids from Alstonia macrophylla with AChE inhibitory activity and cytotoxicity.

Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.

Unlocking InhA: Novel approaches to inhibit Mycobacterium tuberculosis.

Multidrug-resistant tuberculosis continues to pose a health security risk and remains a public health emergency. Antimicrobial resistance result from treatment regimens that are both insufficient and incomplete leading to the emergence of multidrug-resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug-resistant tuberculosis. The impact of tuberculosis on the people suffering from HIV (Human immunodeficiency virus infection) have resulted in the increased research efforts in designing and discovery of novel antitubercular drugs that may result in decreasing treatment duration, minimising the need for multiple drug intake, minimising cytotoxicity and enhancing the mechanism of action of drug. While many drugs are available to treat tuberculosis, a precise and timely cure is still absent. Consequently, further investigation is needed to identify more recent molecular equivalents that have the potential to swiftly remove this disease. Isoniazid (INH), a treatment for tuberculosis (TB), targets the enzyme InhA (mycobacterium enoyl acyl carrier protein reductase), the Mycobacterium tuberculosis enoyl-acyl carrier protein (ACP) reductase, most common INH resistance is circumvented by InhA inhibitors that do not require KatG (catalase-peroxidase) activation, as a result, researchers are trying to work in the area of development of InhA inhibitors which could help in eradicating the era of tuberculosis from the world.

Novel guanidine derivatives targeting leukemia as selective Src/Abl dual inhibitors: Design, synthesis and anti-proliferative activity.

A new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, 1H-, 13C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines. Among all, compound 3b was the most potent, with IC50 of 0.018 µM for normoxia, and 0.001 µM for hypoxia, compared to staurosporine against HL-60 leukemia cell line. To verify the selectivity of this derivative, it was assessed against a panel of tyrosine kinase EGFR, VEGFR-2, B-raf, ERK, CK1, p38-MAPK, Src and Abl enzymes. Results revealed that compound 3b can effectively and selectively inhibit Src/Abl with IC500.25 µM and Abl inhibitory activity with IC500.08 µM, respectively, and was found to be more potent on these enzymes than other kinases that showed the following results: EGFR IC500.31 µM, VEGFR-2 IC500.68 µM, B-raf IC500.33 µM, ERK IC501.41 µM, CK1 IC500.29 µM and p38-MAPK IC500.38 µM. Moreover, cell cycle analysis and apoptosis performed to compound 3b against HL-60 suggesting its antiproliferative activity through Src/Abl inhibition. Finally, molecular docking studies and physicochemical properties prediction for compounds 3b, 3c, and 3 h were carried out to investigate their biological activities and clarify their bioavailability.

Synthesis, growth inhibitory activity against tumor cells, and structure-activity relationship of CGK733 and its analogs.

CGK733 was reported as a compound that inhibited ATM/ATR kinase activities and blocked their checkpoint signaling pathways with great selectivity. However, this paper was subsequently retracted, and the truth about the activity of CGK733 remains unclear. We synthesized various analogs of CGK733 with a modification of the carboxylic acid moiety and/or the aniline derivative moiety to accumulate knowledge of the structure-activity relationship of this compound. Growth inhibitory activity of CGK733 and novel 35 analogs against HeLa S3 cells was evaluated, and the structure-activity relationship revealed that analogs with the 2-naphthyl or 4-fluorophenyl group instead of the benzhydryl group have activity comparable to CGK733 and that the 3-nitro group on the aniline moiety significantly affects the activity.

Bacillus lipopeptides inhibit lipase activity and promote 3T3-L1 preadipocyte differentiation.

Bacillus lipopeptides have been reported to display anti-obesity effects. In the present study, Lipopeptides from Bacillus velezensis FJAT-45028 that consisted of iturin, fengycin and surfactin were reported. The lipopeptides exhibited a strong lipase inhibition activity in a concentration-dependent manner with a half maximal inhibitory concentration of 0.012 mg/mL, and the inhibition mechanism and type were reversible and competitive, respectively. Results of CCK8 assay showed that 3T3-L1 preadipocyte cells were completely viable under treatment of 0.050-0.2 mg/mL lipopeptides for 24 or 48 h. It was found that the lipopeptides could increase lipid droplets in the differentiated 3T3-L1 adipocytes in tested concentration and suppress the expression of peroxisome proliferator-activated receptor gamma (PPARγ). These results indicated the potential anti-obesity mechanism of the tested lipopeptides might be to inhibit lipase activity but not to suppress lipid accumulation in the adipocytes. Moreover, the lipopeptides could elevate glucose utilisation by 14.43%-33.81% in the differentiated 3T3-L1 adipocytes.

Potential of Marine Bacterial Metalloprotease A69 in the Preparation of Peanut Peptides with Angiotensin-Converting Enzyme (ACE)-Inhibitory and Antioxidant Properties.

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g-1 and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC50 values of 1.50 mg mL-1 and 1.66 mg mL-1, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC50 value of 0.71 mg mL-1. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein.

Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads.

Protein hydrolysates from sea cucumber (Apostichopus japonicus) gonads are rich in active materials with remarkable angiotensin-converting enzyme (ACE) inhibitory activity. Alcalase was used to hydrolyze sea cucumber gonads, and the hydrolysate was separated by the ultrafiltration membrane to produce a low-molecular-weight peptide component (less than 3 kDa) with good ACE inhibitory activity. The peptide component (less than 3 kDa) was isolated and purified using a combination method of ACE gel affinity chromatography and reverse high-performance liquid chromatography. The purified fractions were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the resulting products were filtered using structure-based virtual screening (SBVS) to obtain 20 peptides. Of those, three noncompetitive inhibitory peptides (DDQIHIF with an IC50 value of 333.5 µmol·L-1, HDWWKER with an IC50 value of 583.6 µmol·L-1, and THDWWKER with an IC50 value of 1291.8 µmol·L-1) were further investigated based on their favorable pharmacochemical properties and ACE inhibitory activity. Molecular docking studies indicated that the three peptides were entirely enclosed within the ACE protein cavity, improving the overall stability of the complex through interaction forces with the ACE active site. The total free binding energies (ΔGtotal) for DDQIHIF, HDWWKER, and THDWWKER were -21.9 Kcal·mol-1, -71.6 Kcal·mol-1, and -69.1 Kcal·mol-1, respectively. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that HDWWKER could significantly decrease the systolic blood pressure (SBP) of SHRs after intravenous administration. The results showed that based on the better antihypertensive activity of the peptide in SHRs, the feasibility of targeted affinity purification and computer-aided drug discovery (CADD) for the efficient screening and preparation of ACE inhibitory peptide was verified, which provided a new idea of modern drug development method for clinical use.

Synchronous reducing anti-nutritional factors and enhancing biological activity of soybean by the fermentation of edible fungus Auricularia auricula.

Auricularia auricula fermentation was performed to reduce anti-nutritional factors, improve nutritional components, and enhance biological activity of soybean. Results showed that the contents of raffinose, stachyose, and trypsin inhibitor were significantly decreased from initial 1.65 g L-1, 1.60 g L-1, and 284.67 µg g-1 to 0.14 g L-1, 0.35 g L-1, and 4.52 µg g-1 after 144 h of fermentation, respectively. Simultaneously, the contents of polysaccharide, total phenolics, and total flavonoids were increased, and melanin was secreted. The isoflavone glycosides were converted to their aglycones, and the contents of glyctin and genistin were decreased from initial 1107.99 µg g-1 and 2852.26 µg g-1 to non-detection after 72 h of fermentation, respectively. After 96 h of fermentation, the IC50 values of samples against DPPH and ABTS radicals scavenging were decreased from 17.61 mg mL-1 and 3.43 mg mL-1 to 4.63 mg mL-1 and 0.89 mg mL-1, and those of samples inhibiting α-glucosidase and angiotensin I-converting enzyme were decreased from 53.89 mg mL-1 and 11.27 mg mL-1 to 18.24 mg mL-1 and 6.78 mg mL-1, respectively, indicating the significant increase in these bioactivities. These results suggested A. auricula fermentation can enhance the nutritional quality and biological activity of soybean, and the fermented soybean products have the potential to be processed into health foods/food additives.

Activity of OSBPI fungicide fluoxapiprolin against plant-pathogenic oomycetes and its systemic translocation in plants.

Fluoxapiprolin, a novel piperidinyl thiazole isoxazoline fungicide, was developed by Bayer Crop Science in 2012. Despite its well-documented inhibitory activity against plant pathogenic oomycetes such as Phytophthora capsici and Phytophthora infestans, limited information regarding its antifungal spectrum and protective and curative activity is available. Fluoxapiprolin exhibited strong inhibitory activity against Phytophthora spp. and several Pythium spp., with EC50 values ranging from 2.12 × 10-4 to 2.92 µg/mL. It was much more effective against P. capsici in inhibiting mycelial growth, sporangium production, and cystospore germination than at reducing zoospore release. Moreover, fluoxapiprolin displayed both protective and curative activity against P. capsici infection in pepper plants under greenhouse conditions, with systemic translocation capability confirmed by High Performance Liquid Chromatography (HPLC) analysis. The results demonstrated the strong inhibitory activity of fluoxapiprolin against economically important plant oomycete pathogens, including Phytophthora spp. and several Pythium spp., and its certain translocation activity in pepper plants.

Three neo-Clerodane Diterpenoids from Tinospora cordifolia Stems and Their Arginase Inhibitory Activities.

Three neo-clerodane diterpenoids, including two new tinocordifoliols A (1) and B (2) and one known tinopanoid R (3), were isolated from the ethyl acetate-soluble fraction of the 70% ethanol extract of Tinospora cordifolia stems. The structures were elucidated by various spectroscopic methods, including one dimensional (1D) and 2D-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and electronic circular dichroism (ECD) data. The T. cordifolia extract and all isolated compounds 1-3 possessed arginase I inhibitory activities. Among them, 3 exhibited moderate competitive inhibition of human arginase I (IC50 = 61.9 µM). Furthermore, docking studies revealed that the presence of a ß-substituted furan in 3 may play a key role in the arginase I inhibitory activities.

Three Undescribed Furanoditerpenoids from the Tinospora crispa that Inhibit NO Production.

Phytochemical study on the methanol extract of the stems of Tinospora crispa (L.) Hook.f. & Thomson led to the isolation of thirteen compounds including three undescribed cis-clerodane-type furanoditerpenoids (1-3) and ten known ones (4-13). Their chemical structures were determined by IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 2-4, 6 and 8 inhibited moderately NO production in LPS activated RAW 264.7 cells with the IC50 values of 83.5, 57.6, 75.3, 78.1, and 74.7 µM, respectively.

Suaedamas A-D: Four New Compounds from the Aerial Parts of Suaeda maritima with Inhibition of NO Production Activity.

Four new compounds, suaedamas A-D (1-4), and seven known ones (5-11) were isolated from the aerial parts of Suaeda maritima. Their chemical structures were evaluated by the IR, HR-ESI-MS, 1D-, and 2D-NMR, experimental and calculated ECD spectra. Compounds 1-6 inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 29.3 to 85.5 µM, compared to that of the positive control compound, dexamethasone, which showed IC50 value of 13.4 µM.