Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.
The anti-inflammatory drug predinisolone (1) was reduced to 20β-hydroxyprednisolone (2) by the marine endophytic fungus Penicilium lapidosum isolated from an alga. The structural elucidation of 2 was achieved by 1D- and 2D-NMR, MS, IR data. Although, 2 is a known compound previously obtained through microbial transformation, the data provided failed to prove the C20 stereochemistry. To solve this issue, DFT and TD-DFT calculations have been carried out at the B3LYP/6-31+G (d,p) level of theory in gas and solvent phase. The absolute configuration of C20 was eventually assigned by combining experimental and calculated electronic circular dichroism spectra and 3JHH chemical coupling constants.
Hispidin oligomers are styrylpyrone pigments isolated from the medicinal fungi Inonotus xeranticus and Phellinus linteus. They exhibit diverse biological activities and strong free radical scavenging activity. To rationalize the antioxidant activity of a series of four hispidin oligomers and determine the favored mechanism involved in free radical scavenging, DFT calculations were carried out at the B3P86/6-31+G (d, p) level of theory in gas and solvent. The results showed that bond dissociation enthalpies of OH groups of hispidin oligomers (ArOH) and spin density delocalization of related radicals (ArO•) are the appropriate parameters to clarify the differences between the observed antioxidant activities for the four oligomers. The effect of the number of hydroxyl groups and presence of a catechol moiety conjugated to a double bond on the antioxidant activity were determined. Thermodynamic and kinetic studies showed that the PC-ET mechanism is the main mechanism involved in free radical scavenging. The spin density distribution over phenoxyl radicals allows a better understanding of the hispidin oligomers formation.
The synthesis of kojic acid derivative (KAD) from kojic and palmitic acid (C16:0) in the presence of immobilized lipase from Rhizomucor miehei (commercially known as Lipozyme RMIM), was studied using a shake flask system. Kojic acid is a polyfunctional heterocycles that acts as a source of nucleophile in this reaction allowing the formation of a lipophilic KAD. In this study, the source of biocatalyst, Lipozyme RMIM, was derived from the lipase of Rhizomucor miehei immobilized on weak anion exchange macro-porous Duolite ES 562 by the adsorption technique. The effects of solvents, enzyme loading, reaction temperature, and substrate molar ratio on the reaction rate were investigated. In one-factor-at-a-time (OFAT) experiments, a high reaction rate (30.6 × 10-3 M·min-1) of KAD synthesis was recorded using acetone, enzyme loading of 1.25% (w/v), reaction time of 12 h, temperature of 50 °C and substrate molar ratio of 5:1. Thereafter, a yield of KAD synthesis was optimized via the response surface methodology (RSM) whereby the optimized molar ratio (fatty acid: kojic acid), enzyme loading, reaction temperature and reaction time were 6.74, 1.97% (w/v), 45.9 °C, and 20 h respectively, giving a high yield of KAD (64.47%). This condition was reevaluated in a 0.5 L stirred tank reactor (STR) where the agitation effects of two impellers; Rushton turbine (RT) and pitch-blade turbine (PBT), were investigated. In the STR, a very high yield of KAD synthesis (84.12%) was achieved using RT at 250 rpm, which was higher than the shake flask, thus indicating better mixing quality in STR. In a rheological study, a pseudoplastic behavior of KAD mixture was proposed for potential application in lotion formulation.
Death from tuberculosis has resulted in an increased need for early detection to prevent a tuberculosis (TB) epidemic, especially in closed and crowded populations. Herein, a sensitive electrochemical DNA biosensor based on functionalized iron oxide with mercaptopropionic acid (MPA-Fe3O4) nanoparticle and nanocellulose crystalline functionalized cetyl trimethyl ammonium bromide (NCC/CTAB) has been fabricated for the detection of Mycobacterium tuberculosis (MTB). In this study, a simple drop cast method was applied to deposit solution of MPA-Fe3O4/NCC/CTAB onto the surface of the screen-printed carbon electrode (SPCE). Then, a specific sequence of MTB DNA probe was immobilized onto a modified SPCE surface by using the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling mechanism. For better signal amplification and electrochemical response, ruthenium bipyridyl Ru(bpy)32+ was assigned as labels of hybridization followed by the characteristic test using differential pulse voltammetry (DPV). The results of this biosensor enable the detection of target DNA until a concentration as low as 7.96 × 10-13 M with a wide detection range from 1.0 × 10-6 to 1.0 × 10-12 M. In addition, the developed biosensor has shown a differentiation between positive and negative MTB samples in real sampel analysis.
'Mato Peiyu' pomelo (Citrus grandis (L.) Osbeck 'Mato Peiyu') leaves from pruning are currently an agricultural waste. The aim of this study was to isolate essential oils from these leaves through steam distillation (SD) and solvent-free microwave extraction (SFME) and to evaluate their applicability to skin care by analyzing their antimicrobial, antioxidant (diphenyl-1-picrylhydrazyl scavenging assay, β-carotene/linoleic acid assay, and nitric oxide scavenging assay), anti-inflammatory (5-lipoxygenase inhibition assay), and antityrosinase activities. The gas chromatography-mass spectrometry results indicated that the main components of 'Mato Peiyu' leaf essential oils were citronellal and citronellol, with a total percentage of 50.71% and 59.82% for SD and SFME, respectively. The highest bioactivity among all assays was obtained for 5-lipoxygenase inhibition, with an IC50 value of 0.034% (v/v). The MIC90 of the antimicrobial activity of essential oils against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans ranged from 0.086% to 0.121% (v/v). Citronellal and citronellol were the main contributors, accounting for at least 54.58% of the essential oil's bioactivity. This paper is the first to report the compositions and bioactivities of 'Mato Peiyu' leaf essential oil, and the results imply that the pomelo leaf essential oil may be applied in skin care.
The quality of Panax Linn products available in the market is threatened by adulteration with different Panax species, such as Panax quinquefolium (PQ), Panax ginseng (PG), and Panax notoginseng (PN). In this paper, we established a 2D band-selective heteronuclear single quantum coherence (bs-HSQC) NMR method to discriminate species and detect adulteration of Panax Linn. The method involves selective excitation of the anomeric carbon resonance region of saponins and non-uniform sampling (NUS) to obtain high-resolution spectra in less than 10 min. The combined strategy overcomes the signal overlap limitation in 1H NMR and the long acquisition time in traditional HSQC. The present results showed that twelve well-separated resonance peaks can be assigned in the bs-HSQC spectra, which are of high resolution, good repeatability, and precision. Notably, the identification accuracy of species was found to be 100% for all tests conducted in the present study. Furthermore, in combination with multivariate statistical methods, the proposed method can effectively determine the composition proportion of adulterants (from 10% to 90%). Based on the PLS-DA models, the identification accuracy was greater than 80% when composition proportion of adulterants was 10%. Thus, the proposed method may provide a fast, practical, and effective analysis technique for food quality control or authenticity identification.
In this work, manganese (Mn)-doped YFeO3, i.e., YFMxO powders with 0 ≤ x ≤ 0.1, was synthesized by a hydrothermal method to study the influences of doping on its structural, morphological, optical, magnetic, and local electrical properties. The experimental results show that all the samples exhibit an orthorhombic structure with space group Pnma. Refined structure parameters are presented. Morphology images show the shape evolution from layered to multilayered with increasing Mn content. Infrared spectra reveal the characteristic vibrations of the obtained YFMxO samples. From the magnetic study, an increased magnetic moment in the range of 0 ≤ x ≤ 0.075 is observed. The Fe and Y K-edge local structure studies indicate that the valency of Fe and Y is mainly found in the trivalent state, which also indicates that the substitution of Mn ions not only affects the nearest neighbor atomic shell of Fe but also affects the nearest neighbor's local structure of Y atoms. Our results show that the addition of Mn exhibits an evident influence on the local structural and magnetic properties.
Tuberculosis (TB) is a chronic, potentially fatal disease caused by Mycobacterium tuberculosis (Mtb). The dihyrofolate reductase in Mtb (mt-DHFR) is believed to be an important drug target in anti-TB drug development. This enzyme contains a glycerol (GOL) binding site, which is assumed to be a useful site to improve the selectivity towards human dihyrofolate reductase (h-DHFR). There have been previous attempts to design drugs targeting the GOL binding site, but the designed compounds contain a hydrophilic group, which may prevent the compounds from crossing the cell wall of Mtb to function at the whole cell level. In the current study, we designed and synthesized a series of mt-DHFR inhibitors that contain a 2,4-diaminopyrimidine core with side chains to occupy the glycerol binding site with proper hydrophilicity for cell entry, and tested their anti-tubercular activity against Mtb H37Ra. Among them, compound 16l showed a good anti-TB activity (MIC = 6.25 μg/mL) with a significant selectivity against vero cells. In the molecular simulations performed to understand the binding poses of the compounds, it was noticed that only side chains of a certain size can occupy the glycerol binding site. In summary, the novel synthesized compounds with appropriate side chains, hydrophobicity and selectivity could be important lead compounds for future optimization towards the development of future anti-TB drugs that can be used as monotherapy or in combination with other anti-TB drugs or antibiotics. These compounds can also provide much information for further studies on mt-DHFR. However, the enzyme target of the compounds still needs to be confirmed by pure mt-DHFR binding assays.
Endothelial cell dysfunction is considered to be one of the major causes of vascular complications in diabetes. Polyphenols are known as potent antioxidants that can contribute to the prevention of diabetes. Corn silk has been reported to contain polyphenols and has been used in folk medicine in China for the treatment of diabetes. The present study aims to investigate the potential protective role of the phenolic-rich fraction of corn silk (PRF) against injuries to vascular endothelial cells under high glucose conditions in vitro and in vivo. The protective effect of PRF from high glucose toxicity was investigated using human umbilical vein endothelial cells (HUVECs). The protective effect of PRF was subsequently evaluated by using in vivo methods in streptozotocin (STZ)-induced diabetic rats. Results showed that the PRF significantly reduced the cytotoxicity of glucose by restoring cell viability in a dose-dependent manner. PRF was also able to prevent the histological changes in the aorta of STZ-induced diabetic rats. Results suggested that PRF might have a beneficial effect on diabetic patients and may help to prevent the development and progression of diabetic complications such as diabetic nephropathy and atherosclerosis.
This study focuses on the synthesis, characterization, and evaluation of the performance of core shell nanostructure adsorbent for hydrogen sulfide (H2S) capture. Commercial coconut shell activated carbon (CAC) and commercial mixed gas of 5000 ppm H2S balanced N2 were used. With different preparation techniques, the CAC was modified by core shell impregnation with zinc oxide (ZnO), titanium oxide (TiO2), potassium hydroxide (KOH), and zinc acetate (ZnAC2). The core structure was prepared with CAC impregnated by single chemical and double chemical labelled with ZnAC2-CAC (single chemical), ZnAC2/KOH-CAC, ZnAC2/ZnO-CAC, and ZnAC2/TiO2-CAC. Then, the prepared core was layered either with KOH, TiO2, NH3, or TEOS for the shell. The synthesized adsorbents were characterized in physical and chemical characterization through scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) analyzers. Operation of the adsorber column takes place at ambient temperature, with absolute pressure at 1.5 bar. The H2S gas was fed into the column at 5.5 L/min and the loaded adsorbents were 150 g. The performance of synthesized adsorbent was analyzed through the adsorbent's capability in capturing H2S gas. Based on the results, ZnAc2/ZnO/CAC_WOS shows a better adsorption capacity with 1.17 mg H2S/g and a 53% increment compared to raw CAC. However, the degradation of the adsorbents was higher compared to ZnAc2/ZnO/CAC_OS and to ZnAc2/ZnO/CAC_WS ZnAc2/ZnO/CAC_OS. The presence of silica as a shell has potentially increased the adsorbent's stability in several cycles of adsorption-desorption.
The source and quantity of nutrients available to plants can affect the quality of leafy herbs. A study was conducted to compare quality of Cosmos caudatus in response to rates of organic and mineral-based fertilizers. Organic based fertilizer GOBI (8% N:8% P₂O₅:8% K₂O) and inorganic fertilizer (15% N, 15% P₂O₅, 15% K₂O) were evaluated based on N element rates at 0, 30, 60, 90, 120 kg h⁻¹. Application of organic based fertilizer reduced nitrate, improved vitamin C, antioxidant activity as well as nitrogen and calcium nutrients content. Antioxidant activity and chlorophyll content were significantly higher with increased fertilizer application. Fertilization appeared to enhance vitamin C content, however for the maximum ascorbic acid content, regardless of fertilizer sources, plants did not require high amounts of fertilizer.
Honey is a natural product known for its varied biological or pharmacological activities-ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent) with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies.
Evidence shows that honey improves glycemic control in diabetes mellitus. Besides its hypoglycemic effect, studies indicate that honey ameliorates lipid abnormalities in rats and humans with diabetes. The majority of these studies do not examine the mechanisms by which honey ameliorates glycemic and/or lipid derangements. The gut microbiota is now recognized for its ability to increase energy harvest from the diet and alter lipid metabolism of the host. Recently available data implicate a causal role of these gut microbes in the pathophysiology of obesity, insulin resistance, and diabetes mellitus. In this review, we present some of the latest findings linking gut microbiota to pathogenesis of obesity, insulin resistance, and diabetes mellitus. The review also underlines data that demonstrate the beneficial effects of oligosaccharides on various abnormalities commonly associated with these disorders. Based on the similarities of some of these findings with those of honey, together with the evidence that honey contains oligosaccharides, we hypothesize that oligosaccharides present in honey might contribute to the antidiabetic and other health-related beneficial effects of honey. We anticipate that the possibility of oligosaccharides in honey contributing to the antidiabetic and other health-related effects of honey will stimulate a renewed research interest in this field.
Honey is a natural substance with many medicinal properties, including antibacterial, hepatoprotective, hypoglycemic, antioxidant and antihypertensive effects. It reduces hyperglycemia in diabetic rats and humans. However, the mechanism(s) of its hypoglycemic effect remain(s) unknown. Honey comprises many constituents, making it difficult to ascertain which component(s) contribute(s) to its hypoglycemic effect. Nevertheless, available evidence indicates that honey consists of predominantly fructose and glucose. The objective of this review is to summarize findings which indicate that fructose exerts a hypoglycemic effect. The data show that glucose and fructose exert a synergistic effect in the gastrointestinal tract and pancreas. This synergistic effect might enhance intestinal fructose absorption and/or stimulate insulin secretion. The results indicate that fructose enhances hepatic glucose uptake and glycogen synthesis and storage via activation of hepatic glucokinase and glycogen synthase, respectively. The data also demonstrate the beneficial effects of fructose on glycemic control, glucose- and appetite-regulating hormones, body weight, food intake, oxidation of carbohydrate and energy expenditure. In view of the similarities of these effects of fructose with those of honey, the evidence may support the role of fructose in honey in mediating the hypoglycemic effect of honey.
Seventeen methanol extracts from different plant parts of five different Cassia species, including C. timorensis, C. grandis, C. fistula, C. spectabilis, and C. alata were screened against acetylcholinesterase (AChE). C. timorensis extracts were found to exhibit the highest inhibition towards AChE whereby the leaf, stem, and flower methanol extracts showed 94-97% inhibition. As far as we are aware, C. timorensis is one of the least explored Cassia spp. for bioactivity. Further fractionation led to the identification of six compounds, isolated for the first time from C. timorensis: 3-methoxyquercetin (1), benzenepropanoic acid (2), 9,12,15-octadecatrienoic acid (3), β-sitosterol (4), stigmasterol (5), and 1-octadecanol (6). Compound 1 showed moderate inhibition towards AChE (IC50: 83.71 μM), while the other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that the methoxy substitution of 1 formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS) and the hydroxyl group at C5 formed a covalent hydrogen bond with ASP72. Additionally, the OH group at the C3' position formed an interaction with the protein at the acyl pocket (PHE288). This possibly explains the activity of 1 in blocking the entry of acetylcholine (ACh, the neurotransmitter), thus impeding the hydrolysis of ACh.
Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA-FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.
Despite being widely used traditionally as a general tonic, especially in South East Asia, scientific research on Cassia timoriensis, remains scarce. In this study, the aim was to evaluate the in vitro activities for acetylcholinesterase (AChE) inhibitory potential, radical scavenging ability, and the anti-inflammatory properties of different extracts of C. timoriensis flowers using Ellman's assay, a DPPH assay, and an albumin denaturation assay, respectively. With the exception of the acetylcholinesterase activity, to the best of our knowledge, these activities were reported for the first time for C. timoriensis flowers. The phytochemical analysis confirmed the existence of tannins, flavonoids, saponins, terpenoids, and steroids in the C. timoriensis flower extracts. The ethyl acetate extract possessed the highest phenolic and flavonoid contents (527.43 ± 5.83 mg GAE/g DW and 851.83 ± 10.08 mg QE/g DW, respectively) as compared to the other extracts. In addition, the ethyl acetate and methanol extracts exhibited the highest antioxidant (IC50 20.12 ± 0.12 and 34.48 ± 0.07 µg/mL, respectively), anti-inflammatory (92.50 ± 1.38 and 92.22 ± 1.09, respectively), and anti-AChE (IC50 6.91 ± 0.38 and 6.40 ± 0.27 µg/mL, respectively) activities. These results suggest that ethyl acetate and methanol extracts may contain bioactive compounds that can control neurodegenerative disorders, including Alzheimer's disease, through high antioxidant, anti-inflammatory, and anti-AChE activities.
Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 μg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.
Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.