Inhibitory Activity Research Articles

In-vitro antidiabetic activity of ethanolic extract from Khla (Schumannianthus dichotomus Roxb.) rhizome.

Schumannianthus dichotomus Roxb. in Thai, namely “Khla,” is notably distributed in South and South-East Asia regions. In Thai traditional medicine, rhizome has a bland taste, and after decoction, it is used to reduce body heat and fever and treatment of skin diseases. Recently, the methanolic extract of rhizome had reported the hepatoprotective and hypoglycemic activities in mice. Aims of this study were conducted to determine the nutritional value of rhizome and to evaluate α-glucosidase, and α-amylase inhibitory activities of ethanol extract from the rhizome (KE). The rhizome had a high content of dietary fiber and iron, while it was low in calories, fat, and carbohydrates. Thus, it can become an ingredient of a healthy diet. The total phenolic content of KE contained 229.8 ± 6.23 mg of gallic acid equivalent (GAE)/g. There was strongly inhibited α-glucosidase (IC50 = 0.11 ± 0.03 mg/mL) and comparable with the antidiabetic drug acarbose (IC50 = 0.10 ± 0.03 mg/mL). Therefore, KE was slightly inhibited by α-amylase (IC50 = 0.42 ± 0.05 mg/mL), when compared with acarbose (IC50 = 0.016 ± 0.001 mg/mL). Thus, the phytochemicals of different extracts are necessary to be identified. Therefore, the advance techniques were the limitation of our study.

Synthesis, Characterization, and Antidiabetic Evaluation of N-((5-(3- chloro-4-nitrophenyl)-1,3,4-oxadiazol-2-yl) carbamothioyl) Benzamide Derivatives.

A series of novel N-((5-(3-chloro-4-nitrophenyl)-1,3,4-oxadiazol-2-yl) carbamothioyl) benzamide derivatives (2a-2h) were synthesized and characterized for their potential antidiabetic properties. The synthesis involved multi-step reactions starting from 3-chloro-4-nitrobenzoic acid, and the final compounds were purified by recrystallization. The structures were confirmed using melting points, TLC, FTIR, 1 H-NMR, 13C-NMR, and LC-MS. In-silico pharmacokinetic analysis using SwissADME indicated favorable drug-likeness properties for the synthesized compounds, particularly those with electron-withdrawing substituents. In-vitro assays demonstrated significant α-amylase and α-glucosidase inhibitory activities, with compounds 2a, 2g, and 2h showing the highest potency (IC50 values: 23.19-28.61 µM for α-amylase and 23.25-28.25 µM for α-glucosidase), comparable to the standard drug acarbose. The presence of electron-withdrawing groups enhanced the inhibitory effects, while electron-donating groups reduced efficacy. These findings suggest that the synthesized compounds, particularly 2a, 2g, and 2h, hold promise as effective antidiabetic agents.

Design, Synthesis, Anticholinesterase and Antidiabetic Inhibitory Activities, and Molecular Docking of Novel Fluorinated Sulfonyl Hydrazones

Design, Synthesis, Anticholinesterase and Antidiabetic Inhibitory Activities, and Molecular Docking of Novel Fluorinated Sulfonyl Hydrazones

Discovery of a Highly Promising Disulfide Derivative Scaffold as Inhibitor of SARS-CoV-2 Main Protease.

The main protease (Mpro) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) represents a promising target for antiviral drugs aimed at combating COVID-19. Consequently, the development of Mpro inhibitor is an ideal strategy for combating the virus. In this study, we identified twenty-two dithiocarbamates (1 a-h), dithiocarbamate-Cu(II) complexes (2 a-hCu) and disulfide derivatives (2 a-e, 2 i) as potent inhibitors of Mpro, with IC50 value range of 0.09-0.72, 0.9-24.7, and 15.1-111 μM, respectively, through FRET screening. The enzyme kinetics, inhibition mode, jump dilution, and DTT assay revealed that 1 g may be a partial reversible inhibitor, while 2 d and 2 f-Cu are the irreversible and dose- and time-dependent inhibitors, potentially covalently binding to the target. Binding of 2 d, 2 f-Cu, and 1 g to Mpro was found to decrease the stability of the protein. Additionally, DTT assays and thermal shift assays indicated that 2 f-Cu and 2 d are the nonspecific and promiscuous cysteine protease inhibitor. ICP-MS implied that the inhibitory activity of 2 f-Cu may stem from the uptake of Cu(II) by the enzyme. Cytotoxicity assays demonstrated that 2 d and 1 g exhibit low cytotoxicity, whereas 2 f-Cu show certain cytotoxicity in L929 cells. Overall, this work presents two promising scaffolds for the development of Mpro inhibitors to combat COVID-19.

Uncovering the Potential ofO-Prenylated 3-aryl-benzopyran Derivatives as Osteogenic and Cancer Cell Growth Inhibitory Agents.

Naturally, O-prenylation of 3-aryl-benzopyrans enhances the biological activities of these compounds. In this study, substituted O-prenylated 3-aryl-benzopyrans (21a-c, 22a-c, 23a-c, 24a-c 25a-c, 27 and 28) were synthesized and evaluated for osteogenic and cancer cell growth inhibitory potentials using cell-based in-vitro models. Amongst the target compounds, 21a, 22b, 23c, and 24c showed good osteogenic activity at 1 pM concentration, whereas 26 and 27 showed osteogenic activity at 100pM and 10nM, respectively. Compounds 21a, 22b, and 23c showed good cancer cell growth inhibitory activity against breast cancer cells (MCF-7 and MBA-231). Amongst active compounds, 27 presented the best anticancer activity against MDAMB-231 cells with selectivity towards non-cancerous cells [IC50 3.76 µM with SI 13.3]. The in-silico study of compounds showed their structural complementarities with the LBD of estrogen receptors and compliance with dragability parameters.

Comparative Investigation of Punica granatum L. Phytochemical Analysis and In-vitro Antimicrobial Activity Screening Using Roots Samples from Urban and Rural Areas Uses Five Different Solvent Extracts .

Antimicrobial, fungal, and bacterial infections in the human body are the causes of foodborne, waterborne, and airborne illnesses as well as those that arise naturally. Because nosocomial usage increases the presence of both complex and non-complicated microorganisms, urinary tract infections (UTIs) are most common, especially in women. Antibiotics are an amazing tool in the fight against infections; the WHO survey 2022(1) noted that microbial and fungal infections account for 1.5 billion deaths worldwide. The production of natural remedies is becoming a serious concern and is progressing quickly as well. Many phytochemical compounds from flora could be used to treat these infections based on the effect of the respective integrated organism’s host defense efficacy. The therapeutic or pathogen-resistant capacity of the phytochemicals under different chemical classes may reverse and control the antibiotic resistance of resistant pathogens. The aim of the study is to find the roots of Punica granatum L from the urban and rural regions to find the phytochemical efficacy from extracts like petroleum ether, chloroform, ethanol, carbinol and aqueous. It revealed that a high yield of pharmacological compounds is from a rural sample’s carbinol extract. Quantitative analysis showed the presence of high amounts of majorly anti-cancerous agents in high peaks from rural samples. Using the well diffusion method, in-vitro antimicrobial activity was determined. Against their negative controls, the inhibition activity of Escherichia coli showed a 22 mm inhibition zone from the ethanol extract, Staphylococcus aureus showed a 21 mm inhibition zone, and fungal pathogens such as Candida albicans and Candida krusei showed a 21 mm maximum inhibition zone from the carbinol extracts.

Unveiling the Therapeutic Potential of Basella alba: A Comprehensive Investigation into Its Anti-arthritic Properties, Phytochemical Profile, and Molecular Docking Insights.

Polyherbal antidiabetic tablets were formulated, evaluated and compressed by combining the powder extract of Nigella sativa, Trigonella foenum, and Glycyrrhiza Glabra. A number of tests were carried out, including a uniformity weight test, an assessment of the tablets’ hardness and friability, an ash value, moisture content, an extractive value that is soluble in water or alcohol, density (bulk and tapped), repose angle, Carr’s index, disintegration time with preliminary phytochemical screening. The tablet also had ex-vivo antidiabetic performance to enzymes alpha-amylase as well as glucosidase. To ensure the presence of active ingredients, thin-layer chromatography was performed. Column chromatography as performed using silica gel G as a stationary phase. The column of material was created using acetic acid, toluene, and ethyl acetate. As follows: (5.0:4.2:0.8) for 10 ml. The mobile phase of the sample, which contains toluene, ethyl acetate, acetic acid (50:42:8) and fractions, was isolated, collected and sent to IIT Bombay for GCHRMS analysis. In GCHRMS, the chemical constituent was found to be 2 H-Pyran-2-one, tetrahydro-4-hydroxy-4-methyl-, Tetrahydro [2 , 2’] bifuranyl-5-one, 1H-Benzimidazole, 2-(1-methylethyl)-, Bifenthrin, Propionamide, 2,2-diphenyl-N-(2-pyridinyl)-, Dihydromyristicin, 2-Dodecanone, di-p-Tolyl sulfone. The tablets showed promising results for alpha-amylase and alpha-glucosidase inhibition activities.

Design, synthesis, and evaluation of chalcone derivatives as xanthine oxidase inhibitors

Xanthine oxidase (XO) is an important enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid in the catabolism of purines in humans. This makes XO a well-recognized target in alleviating hyperuricemia. The present study adapted a structure-based drug discovery approach to develop potent and low-toxicity XO inhibitors with the chalcone skeleton. We introduced a carboxyl group and a hydroxyl group to the B ring and modified the A ring. 35 chalcone derivatives were designed and synthesized. All the 35 derivatives exhibited higher XO inhibition activities (IC50=0.064-0.559μM) compared with allopurinol (IC50=2.588μM). Their high affinity was attributed to strong hydrogen bond interactions formed between the introduced carboxyl and hydroxyl groups with key amino acid residues in XO. SAR analysis disclosed that carboxyl, hydroxyl, ethyl (12c), methylamino (12h), dimethylamino (12i), indolin (13k), and indol (13l) groups played important roles in improving the whole molecules' inhibition potency against XO. ADME predictions and cytotoxicity assays suggested their pharmacokinetic characteristics and biocompatibility were desirable. Additionally, 12c exhibited a significant hypouricemic effect on potassium oxonate-induced hyperuricemia rats after orally administrated at a dose range of 10-40mg/kg, representing a promising anti-hyperuricemia potential for further optimization and development.

Bioguided Fractionation and Isolation of Natural Antidiabetic Agents from Polyherbal Tablet.

Polyherbal antidiabetic tablets were formulated, evaluated and compressed by combining the powder extract of Nigella sativa, Trigonella foenum, and Glycyrrhiza Glabra. A number of tests were carried out, including a uniformity weight test, an assessment of the tablets’ hardness and friability, an ash value, moisture content, an extractive value that is soluble in water or alcohol, density (bulk and tapped), repose angle, Carr’s index, disintegration time with preliminary phytochemical screening. The tablet also had ex-vivo antidiabetic performance to enzymes alpha-amylase as well as glucosidase. To ensure the presence of active ingredients, thin-layer chromatography was performed. Column chromatography as performed using silica gel G as a stationary phase. The column of material was created using acetic acid, toluene, and ethyl acetate. As follows: (5.0:4.2:0.8) for 10 ml. The mobile phase of the sample, which contains toluene, ethyl acetate, acetic acid (50:42:8) and fractions, was isolated, collected and sent to IIT Bombay for GCHRMS analysis. In GCHRMS, the chemical constituent was found to be 2 H-Pyran-2-one, tetrahydro-4-hydroxy-4-methyl-, Tetrahydro [2 , 2’] bifuranyl-5-one, 1H-Benzimidazole, 2-(1-methylethyl)-, Bifenthrin, Propionamide, 2,2-diphenyl-N-(2-pyridinyl)-, Dihydromyristicin, 2-Dodecanone, di-p-Tolyl sulfone. The tablets showed promising results for alpha-amylase and alpha-glucosidase inhibition activities.

Chemical Constituents and their Nanoemulsion Properties of Ethyl Acetate Crude Extract from Black Galingale Rhizome

Black galingale is a medicinal plant that has medicinal properties. The major constituents found in black galingale rhizomes are flavonoids, which display antioxidant activities. Therefore, in this research, the focus is to isolate and structurally determine bioactive compounds from the ethyl acetate extract of black galingale rhizomes and evaluate their antioxidant and antimicrobial activity, The black galingale rhizomes were extracted by maceration using ethyl acetate as a solvent. the compounds were isolated by column chromatography using hexane: ethyl acetate as an eluent solvent system. The isolated compounds were examined and characterized using FT-IR, UV-Vis, and NMR techniques, examined antioxidant activity by DPPH assay, and antimicrobial activity. From the extraction of ethyl acetate extract, it was found that 4 pure flavonoid compounds could be extracted. The FT-IR spectral data of 4 compounds showed a unique vibration corresponding to OH stretching, CH stretching, C=O stretching, C=C stretching of an aromatic ring, and C-O-C bond. Antioxidant activity testing by DPPH assay found 5-hydroxy-3,7-dimethoxyflavone (1) to have the highest antioxidant activity at 73.79% compared to the standard Trolox with 133.37±1.60 mM. Antimicrobial activity testing found that 3,5,7-trimethoxyflavone (3) showed the best growth inhibition activities against B. megaterium and S.aureus, Moreover, it studies the nanoemulsion properties of 5-hydroxy-3,7-dimethoxyflavone (1) was found stable with a nanoparticle size of 21.1 nm, a zeta potential of-49.7 mV, and has PDI of 0.227. Therefore, this research shows that the extract from black galingale rhizome could be used as an active ingredient in the cosmetics industry.

Evaluating cortical excitatory and inhibitory activity through interictal intracranial electroencephalography in mesial temporal lobe epilepsy.

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms.

In silico design and ADMET evaluation of new inhibitors for PIM1 kinase using QSAR studies, molecular docking, and molecular dynamic simulation

The proviral Integration site of Moloney (PIM) kinase is highly expressed in various diseases, including cancer, making the development of selective inhibitors for this protein important. A series of PIM1 inhibitors, triazolo [4, 3-b] pyridazin-3-yl-quinoline derivatives, have been studied to design new inhibitors. The activity and structural features of these derivatives were investigated to understand their interactions with PIM1 using molecular docking, molecular dynamic simulation, and QSAR techniques.In a study of 30 compounds using the structure-activity technique and the MLR method, a linear model with R2train = 0.91 and R2test = 0.96 was obtained. The model utilized descriptors such as RDF080v, RDF105v, RDF135v, Mor03v, and H046 to express the structural characteristics of the inhibitors. To enhance the model, the SVR non-linear method with the RBF function was also used, resulting in an improved model with R2train = 0.98 and R2test = 0.98.Furthermore, the molecular docking technique was employed to investigate the interaction of compounds with high (compound 25) and low (compound 13) inhibitory activity. It was observed that the rings with nitrogen atoms interacted with the protein. The molecular binding results indicate that groups such as OMe and rings with Nitrogen can enhance the inhibitory activity of the compounds. Additionally, oxygen and nitrogen atoms contribute to an increased number of hydrogen bonds, thereby increasing the inhibitory activity of the compounds.Additionally, the stability and bonding modes of active and inactive compounds were studied using molecular dynamic simulation. Based on the results, four new inhibitors were designed, demonstrating better inhibition efficiency with the PIM1 kinase compared to the reference compounds. Moreover, the designed compounds underwent evaluation for ADMET, yielding promising results.

Discovery of Potential Inhibitors of CDK1 by Integrating Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation Studies, and Evaluation of Their Inhibitory Activity.

The ability of CDK1 to compensate for the absence of other cell cycle CDKs poses a great challenge to treat cancers that overexpress these proteins. Despite several studies focusing on the area, there are no FDA-approved drugs selectively targeting CDK1. Here, the study aimed to develop potential CDK1 selective inhibitors through drug repurposing and leveraging the structural insights provided by the hit molecules generated. Approximately 280,000 compounds from DrugBank, Selleckchem, Otava and an in-house library were screened initially based on fit values using 3D QSAR pharmacophores built for CDK1 and subsequently through Lipinski, ADMET, and TOPKAT filters. 10,310 hits were investigated for docking into the binding site of CDK1 determined using the crystal structure of human CDK1 in complex with NU6102. The best 55 hits with better docking scores were further analyzed, and 12 hits were selected for 100 ns MD simulations followed by binding energy calculations using the MM-PBSA method. Finally, 10 hit molecules were tested in an in vitro CDK1 Kinase inhibition assay. Out of these, 3 hits showed significant CDK1 inhibitory potential with IC50 < 5 μM. These results indicate these compounds can be used to develop subtype-selective CDK1 inhibitors with better efficacy and reduced toxicities in the future.

Preparation and Tumor Inhibitory Activity of Tricin from Carex Meyeriana Kunth

This study describes the purification and preparation of tricin (5, 7, 4-trihydroxy-3, 5-dimethoxyflavone) from Carex Meyeriana Kunth via adsorption and desorption using macroporous resins and high-performance liquid chromatography. Six resins were tested to evaluate the static adsorption and desorption capacities. The HPD-300 resin was selected as the adsorption material to enrich tricin because of its suitable adsorption and desorption capacities. Adsorption thermodynamics and kinetics were studied on HPD-300 resin, and the results agreed with the Langmuir model and quasi-second-order kinetics model, respectively. The parameters of the dynamic adsorption and desorption tests were then optimized. The purity of tricin increased from 2.6 mg/g to 45.1 mg/g with a recovery yield of 76.4% after purification using HPD-300 resin. Then, Prep-HPLC was used to further purify tricin. The purity of tricin reached 99.4%, with a recovery yield of 78.0% thereafter. Tricin exerts an inhibitory effect on the proliferation of various tumor cells, including gastric cancer SGC-7901 cells. It significantly suppresses cell colony formation while also altering cell cycle progression metabolism by decreasing the proportion of cells in the G0/G1 phase and increasing the proportion in the S and G2/M phases. Additionally, tricin affects the efficiency of SGC-7901 cell lactate production, ATP content, and glucose uptake. These findings suggest that tricin may impede tumor cell proliferation through its impact on cell cycle progression and energy metabolism.

Effective Synthesis of C20-epi-Isothiocyanato-Salinomycin and Its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, Hela, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

Potential Piperolactam A Isolated From Piper betle as Natural Inhibitors of Brucella Species Aminoacyl-tRNA Synthetase for Livestock Infections: In Silico Approach.

Brucellosis is an important global zoonosis caused by the bacterium Brucella sp. Brucellosis causes abortions, reproductive failure and reduced milk production, resulting in significant economic losses. Brucella species are reported to be resistant to antibiotics, which makes treatment difficult. The urgency of discovering new drug candidates to combat Brucella's infection necessitates the exploration of novel alternative agents with unique protein targets. Aminoacyl-tRNA synthetases (aaRSs), which have fundamental functions in translation, inhibit this process, stop protein synthesis and ultimately inhibit bacterial growth. The purpose of this study was to isolate piperolactam A compounds from the methanol extract of Piper betle leaves that have potential as antibacterials to inhibit the growth of Brucella sp. causing brucellosis in livestock and to analyse the mechanism of inhibitory activity of piperolactam A compounds against the aaRS enzyme through a molecular docking approach in silico. Piperolactam A was isolated from P. betle by column chromatography and characterized by UV, IR, 1D and 2D NMRs and MS, then tested for their inhibition mechanism against the enzymes threonyl-tRNA synthetase, leucyl-tRNA synthetase (LeuRS) and methionyl-tRNA synthetase in silico. The result in silico test is that piperolactam A has the potential to inhibit LeuRS enzyme with the greater binding affinity.

Isolation of Novel Compounds from Lepidium sativum Seeds and Evaluation of Their Potential Anti-tumor Activity.

Four undescribed compounds including a pair of enantiomers of a dihydroarylnaphthalene lignan [(±)-1], an arylnaphthalene lignan (2), and an indoleacetic acid ester (3), together with four known compounds (4－7), were isolated from the seeds of Lepidium sativum. Their structures were identified by HRMS and NMR spectroscopic data, and the absolute configuration of these compounds were assigned by ECD data in combination with quantum chemical calculations. Compound (-)-1had weak inhibitory activity against HeLa cell line with an IC50value of 60.23 ± 3.51 μM, and compound (+)-1presented moderate inhibitory effect against HeLa cell line with an IC50value of 19.99 ± 1.00 μM (IC50value of the positive control was 0.40 ±0.02 μM).

Inhibitory Effects of Polyphenols from Equisetum ramosissimum and Moringa peregrina Extracts on Staphylococcus aureus, Collagenase, and Tyrosinase Enzymes: In vitro Studies

Background: Skin problems caused by oxidative stress lead to the activation of collagenase and tyrosinase enzymes, contributing to skin aging, discoloration, and infections. Equisetum ramosissimum and Moringa peregrina were assessed for their potential uses in treating various skin conditions. Objective: The present research aimed to investigate the positive effects of polyphenols in Equisetum ramosissimum and Moringa peregrina extracts as potential cosmetic products for the treatment of different skin conditions. Methods: Total phenolic and flavonoid contents, antioxidants, and anti-collagenase and anti-tyrosinase activities of plant extract mixtures (PEM) at different ratios of (M. peregrina: E. ramosissimum) were determined using standard procedures. Inhibitory effects of PEM against acne-causing Staphylococcus aureus (ATCC 29213) were evaluated using the diameter (cm) of the inhibition zone method. A cream formulation containing PEM was developed and characterized for stability and potential skin irritation in rats using standard procedures. Results: The PEM at a ratio of (2:1) showed the highest total phenolic and flavonoid content (150.15 ± 2.8 mg/g, equivalent to gallic acid, and 41.5 ± 1.2 mg/g, equivalent to quercetin, respectively). Antioxidant activities for PEM (2:1) were also optimal, as determined by the DPPH and ABTS methods (IC50 = 7.06 ± 0.12 µg/mL and 53.29 ± 3.3 µg/mL, respectively). Furthermore, PEM (2:1) exhibited superior inhibitory activities against collagenase and tyrosinase enzymes (IC50 = 32.4 ± 1.19 µg/mL and 8.4 ± 1.19 µg/mL, respectively). Antimicrobial activity of PEM (2:1) tested on S. aureus showed the largest zone of growth inhibition (2.8 cm) at a concentration of 60 mg/mL. Studies on the PEM (2:1) cream formulation revealed that it remained stable under room conditions. Skin irritation tests on rats showed no signs of oedema or erythema after treatment. Conclusion: The PEM with a ratio of (2:1) demonstrated optimal activity as an oxidative stress-neutralizing agent, inhibitor of enzymes responsible for skin aging and hyperpigmentation, and antibacterial agent. The cream formulation containing PEM exhibited physical stability and no detectable risk of skin irritation throughout the research procedures.

Design and Synthesis of Pyridyl and 2-Hydroxyphenyl Chalcones with Antitubercular Activity

A focussed library of pyridyl and 2-hydroxyphenyl chalcones were synthesized and tested for growth inhibitory activity against Mycobacterium tuberculosis H37Rv, and normal and cancer breast cell lines. Pyridyl chalcones bearing lipophilic A-ring, e.g., dichloro-phenyl-(14), pyrene-1-yl (20)- and biphenyl-4-yl (21) moieties were found to be the most potent of the series inhibiting the growth of M. tuberculosis H37Rv with IC90 values ranging from 8.9–28 µM. Aryl chalcones containing a 3-methoxyphenyl A-ring and either p-Br-phenyl (25) or p-Cl-phenyl (26) B-rings showed an IC90 value of 28 μM. Aryl-chalcones were generally less toxic to HepG2 cells compared to pyridyl-chalcones. Dose-dependent antiproliferative activity against MDA468 cells was observed for trimethoxy-phenyl (16) and anthracene-9-yl (19) pyridyl-chalcones with IC50 values of 0.7 and 0.3 µM, respectively. Docking studies revealed that chalone 20 was predicted to bind to the M. tuberculosis protein tyrosine phosphatases B (PtpB) with higher affinity compared to a previously reported PtpB inhibitor.

In Vitro COX Inhibitory Activity, LC-MS Analysis and Molecular Docking Study of Silene vulgaris and Stellaria media.

Silene vulgaris (Moench) Garcke and Stellaria media (L.) Vill is a perennial wild weed species belonging to the Caryophyllaceae family and is widely available and abundant in the environment. The present study has aimed to evaluate the anti-inflammatory potential of two underutilized wild edible plants, Silene vulgaris (Moench) Garcke and Stellaria media (L.) Vill. fractions employing in-vitro COX inhibitory assay. Invitro COX-2 inhibitory potential of MESV and MESM fractions was carried out using BioVisionR "COX Activity Assay Kit (Fluorometric)". LC-MS analysis of selected fractions was conducted to identify bioactive compounds that were further validated for their affinity determination toward target enzymes employing molecular docking studies using the LibDock program. In-vitro COX inhibitory assay revealed that hexane fraction of S. vulgaris (HFSV) and hexane fraction of S. media (HFSM) caused impressive inhibition of COX-2 enzyme with IC50 values 1.38 µg/mL and 1.51 µg/mL respectively. Further, LC-MS analysis revealed the presence of 46 compounds in HFSV and 44 compounds in HFSM respectively. Amongst identified bioactive compounds in HFSV and HFSM, sinapinic acid and syringic acid showed good docking scores with COX-2 i.e., 89.256, and 82.168 respectively. Also, the availability of chrysin in HFSM and rhamnetin in HFSV exhibited good docking scores i.e., 115.092, and 112.341 with a selective affinity towards COX-2. The findings of in-vitro COX Inhibitory Activity and molecular docking studies highlighted the impressive anti-inflammatory properties of S. vulgaris and S. media, and require further investigations to establish them as therapeutic candidates in the management of inflammation and related issues.