IC50 Values In Range Research Articles

Discovery and synthesis of novel phenoxyacetate ester Schiff base α-glucosidase inhibitors

A phenoxyacetate ester Schiff base lead compound 4a (ZINC20073984) was firstly discovered through molecular docking screening and molecular dynamics (MD) simulation, which could be used as an α-glucosidase (PDB: 3A4A) inhibitor. Then a series of α-glucosidase inhibitors 4b-4r with novel structures were designed and synthesized with the lead ZINC20073984 as a template. The results of in vitro α-glucosidase inhibitory activity show that the synthesized phenoxyacetate ester Schiff base compounds 4e, 4o-4r (IC50 values range from 5.44 ± 0.52 μM to 33.67 ± 9.1 μM) exhibit good activity. Among them, ethyl (Z)-2-(2,4-dinitro-5-(2-(1-(2,4,6-trimethoxyphenyl) ethylidene) hydrazineyl) phenoxy) acetate (4r) and ethyl (Z)-2-(2,4-dinitro-5-(2-(1-(1-(4-ethoxyphenyl) ethylidene) hydrazineyl) phenoxy) acetate (4p) exert the best inhibitory activity, with IC50 values of 5.44 ± 0.52 μM and 5.80 ± 1.4 μM, respectively, which are superior to the standard drug acarbose (IC50 = 8.36 ± 0.02 μM). Molecular docking results indicate that the good inhibitory activity of 4r and 4p may be attributed to multiple hydrogen-bonding interactions with the α-glucosidase. Furthermore, the drug-likeness of all synthesized compounds was evaluated using the pkCSM tool, and ADMET predictions were conducted for compound 4r. The results demonstrated that all compounds follow Lipinski’s rules, and 4r possesses favorable pharmaceutical properties. In an in vitro cytotoxicity assay, the most potent 4r shows non-cytotoxicity to the 3T3 cells with an CC50 value > 40 µM. In both antioxidant and anti-cancer capacity assays, compound 4r has demonstrated promising potential. The results of this study might be helpful in the discovery of new drugs for the treatment of diabetes mellitus type-2 and bladder cancer.

Design, Synthesis of Flurbiprofen Based 1,3,4-Oxadiazoles and Constrained Anticancer, Antioxidant Agents: In silico Docking Analysis.

Flurbiprofen, a primary component of a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis, and is a considerable interest in medicinal chemistry due to its demonstrated potential as an effective agent in various therapeutic applications. In consideration of the 1,3,4-oxadiazole therapeutic potential and anticancer activity, a new series of flurbiprofen scaffolds have been prepared through a straightforward reaction between 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-1,3,4-oxadiazole-2-thiol (4) and various organic active 2-chloro-N-phenyl acetamides (5). The synthesized series (6a-6k) was characterized using a combination of spectroscopic techniques, including FT-IR, mass, 1H-NMR, and 13C NMR, followed by physical data. The cytotoxicity of the newly synthesized congeners was investigated against MCF-7 (human breast cancer cell line) and A-549 (human lung carcinoma epithelial) cell lines and anti-inflammatory activity as DPPH and H2O2 radical scavenging ability. In the series, analogues 6c, 6e, 6h, and 6k showed excellent inhibitory activity against MCF-7 cells in the range of IC50 values of 9.10-13.67 μg mL-1 compared to DXN (IC50=9.24 μg mL-1). In this series, analogues 6c, 6f, 6h, and 6j show remarkable H2O2 radical scavenging inhibition IC50 of 48.25±0.21, 47.33±0.15, 51.10±0.25, and 44.40±0.07 μM by using ascorbic acid as a standard, whose IC50 is 49.90±0.27 μM. According to the docking results, the most potent cytotoxic compounds have a stronger binding affinity with the Flurbiprofen complex (PDB: 1R9O) because of their interactions with residues such as Arg416(A), Trp103(A), Phe97(A), Gly279(A), Ile188(A), Glu283(A), Thr287(A), Val462(A), Phe459(A), Leu345(A), Ile417(A), and Cys418(A). Furthermore, in silico drug-likeness prediction analysis suggested that the majority of the synthesized compounds exhibit good oral bioavailability based on their Lipinski's Rule of Five and toxicity using ADME/Tox predictions.

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.

Novel benzimidazole-based azine derivatives as potent urease inhibitors: synthesis, in vitro and in silico approach.

Aim: In light of various biological activities of benzimidazole and azines, this study focuses on reporting novel derivatives of benzimidazole nucleus.Methods: Twenty novel azines of benzimidazole were synthesized, characterized and tested for in vitro urease inhibitory activity.Results: All these derivatives showed excellent to good inhibition in the range of IC50 values 14.21±1.87 to 76.11±1.81μM by comparing with standard thiourea 21.14±0.42μM. Docking studies were performed for the targeted benzimidazole derivatives to understand the binding mechanics. The results indicated higher binding efficacy compared with the reference inhibitor.Conclusion: This work identifies potential lead candidates for novel urease inhibitors, which with industrial support may be harnessed for the development of new drugs.

Experimental and computational profiling of novel bis-Schiff base derivatives bearing α-naphthalene moiety as potential tyrosinase inhibitors

A library of novel bis-Schiff base derivatives (2a-u) of α-naphthalene moiety was successfully synthesized by four step reactions. Following structural elucidation, these products were evaluated for their in vitro tyrosinase inhibitory potential. In the series, nine derivatives (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) attributed excellent inhibitory activity in the range of IC50 values from 2.3 ± 1.7 to 17.6 ± 0.9 µM superior to the standard drug kojic acid. Similarly, four compounds showed significant activities near to the standard while the remaining eight compounds displayed good to moderate inhibition with IC50 values from 29.3 ± 2.9 to 63.2 ± 1.1 µM. The molecular docking investigations for most active compounds (2e, 2r, 2t, 2 g, 2 u, 2p, 2a, 2d, and 2 h) form high stability in binding site of the tyrosinase active site, than standard kojic acid. Frontier molecular orbitals, such as HOMO and LUMO to show the charge transfer from molecule to biological medium and MEP map to show the chemically reactive zone appropriate for drug action, are calculated using TD-DFT. Besides, the drug-likeness prediction showed that these compounds showed a desirable property, such as high intestinal absorption, large volume of distribution, good BBB penetration, and low toxicity. These bis-Schiff bases have a high oral bioavailability, which can categorized as a unique drug candidate in future.

Synthesis of Novel Benzimidazole Analogs for Neurodegenerative Diseases by Targeting Prolyl Oligopeptidase

AbstractA novel series of benzimidazole hydrazone‐Schiff bases have been prepared through multi‐step reaction process and structurally confirmed by13C‐,1H‐NMR and HR‐MS (ESI) spectroscopic techniques and evaluated against prolyl oligopeptidase (POP) inhibitory activity. In the series, eleven derivatives 20, 14 15, 19, 10, 9, 11, 4, 5, 18, and 21 revealed excellent inhibition potential having IC50 values from (IC50=1.44±0.08 μM) to (IC50=5.66±0.48 μM). However, six out of twenty compounds 12, 16, 13, 17, 22, and 3 attributed significant activity while, three compounds were found good active in the range of IC50 values 10.43±0.57 to 11.45±0.63 μM. The docking studies indicates that the hydrazone moiety show an imperative part in binding with one of the catalytic residues (Arg643) in the substrate binding region of POP enzyme. The excellent inhibitions of these compounds for POP enzyme may lead them to be a good candidates for drug against neurodegenerative diseases.

Tri-aryl antimony(V) hydroximato and hydroxamato complexes: Combining lipophilic Sb(III/V) and hydroxamic acids in combating Leishmania

Six novel tri-aryl antimony(V) hydroximato complexes (3–8) with composition [SbAr3(O2NCR)] (3: Ar = Ph, R = o-(OH)Ph, 4: Ar = Ph, R = Me, 5: Ar = Ph, R = Ph; 6: Ar = Mes, R = Me, 7: Ar = Mes, R = Ph, 8: Ar = Mes, R = o-(OH)Ph (where Ph = phenyl, Me = methyl, Mes = mesityl)), were synthesised and evaluated for anti-parasitic activity towards Leishmania major (L. major) promastigotes and amastigotes. Complexes of the form [SbAr3(O2NCR)], with the dianionic hydroximato ligand binding O,O′-bidentate to the Sb(V) centre, exist in the solid-state for the mesityl-derived complexes. In contrast, the phenyl-ligated Sb(V) complexes crystallise as the hexacoordinate, hydroxamato species [SbPh3(O2NHC(OH))], with the OH ligand derived from entrained H2O in the crystallisation solvent. It is found that both the aryl and hydroximato ligands are found to influence the bioactivity of the Sb(V) complexes. Complexes 3–8 exhibited varied anti-promastigote activity with IC50 values ranging from 1.53 μM for 6 to 36.0 μM for 3, also reflected in varied anti-amastigote activity with a percentage infection range of 5.50% for 6 to 29.00% for 3 at a concentration of 10 μM. The complexes were relatively non-toxic to human fibroblasts with an IC50 value range of 59.3 μM (7) to ≥100 μM (3–6, 8), and exhibited varied toxicity towards J774.1 A macrophages (IC50: 3.97 (6) to ≥100 (8) μM). All complexes showed enhanced activity compared to the parent hydroxamic acids.

A new framework for novel analogues of pazopanib as potent and selective human carbonic anhydrase inhibitors: Design, repurposing rational, synthesis, crystallographic, in vivo and in vitro biological assessments

Herein, we describe the design and synthesis of novel aryl pyrimidine benzenesulfonamides APBSs 5a-n, 6a-c, 7a-b, and 8 as pazopanib analogues to explore new potent and selective inhibitors for the CA IX. All APBSs were examined in vitro for their promising inhibition activity against a small panel of hCAs (isoforms I, II, IX, and XII). The X-ray crystal structure of CA I in adduct with a representative APBS analogue was solved. APBS-5m, endowed with the best hCA IX inhibitory efficacy and selectivity, was evaluated for antiproliferative activity against a small panel of different cancer cell lines, SK-MEL-173, MDA-MB-231, A549, HCT-116, and HeLa, and it demonstrated one-digit IC50 values range from 2.93 μM (MDA-MB-231) to 5.86 μM (A549). Furthermore, compound APBS-5m was evaluated for its influence on hypoxia-inducible factor (HIF-1α) production, apoptosis induction, and colony formation in MDA-MB-231 cancer cells. The in vivo efficacy of APBS-5m as an antitumor agent was additionally investigated in an animal model of Solid Ehrlich Carcinoma (SEC). In order to offer perceptions into the conveyed hCA IX inhibitory efficacy and selectivity in silico, a molecular docking investigation was also carried out.

Discovering the anti-diabetic potential of thiosemicarbazone derivatives: In vitro α-glucosidase, α-amylase inhibitory activities with molecular docking and DFT investigations

This work describes the synthesis of para-substituted thiosemicarbazone derivatives by refluxing 4-ethoxybenzaldehyde (1) and 4-nitrobenzaldehyde (2) with thiosemicarbazide in ethanol with acetic acid catalyst. The resultant thiosemicarbazones were then treated with various phenacyl bromides to get the product compounds. 1H NMR and EI-MS spectroscopic methods were employed to confirm the structures of these derivatives and screened the compounds for their in vitro α-glucosidase and α-amylase inhibitory activities. Six compounds (4e, 3e, 3c, 3b, 4b, and 4c) exhibited highest α-glucosidase activity in the range of IC50 values of 2.81 ± 1.92 to 16.16 ± 0.15 µM. Similar to this, five compounds (3e, 4e, 3b, 3c, and 4c) attributed excellent inhibitory activity in the range of IC50 values from 3.12 ± 0.13 to 16.56 ± 0.17 µM against the α-amylase enzyme when compare with the standard acarbose. The density functional theory (DFT) study demonstrated the stability, bioactivity, and charge transfer of the compounds, while the molecular docking analysis has provided significant understanding of how the compounds interact with the enzymes. These findings provide prospective directions for the development of innovative therapeutic candidates to regulate postprandial glucose levels in diabetic patients.

Synthesis, cytotoxicity and antioxidant activity of new conjugates of N-acetyl-d-glucosamine with α-aminophosphonates

A series of the first conjugates of N-acetyl-d-glucosamine with α-aminophosphonates was synthesized using the Kabachnik-Fields reaction, the Pudovik reaction, a copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) and evaluated for the in vitro cytotoxicity against human cancer cell lines M − HeLa, HuTu-80, A549, PANC-1, MCF-7, T98G and normal lung fibroblast cells WI-38. The tested conjugates, with exception of compound 21b, considered as a lead compound, were either inactive against the used cancer cells or showed moderate cytotoxicity in the range of IC50 values 33−80 μM. The lead compound 21b, being non cytotoxic against normal human cells WI-38 (IC50 = 90 μM), demonstrated good activity (IC50 = 17 μM) against breast adenocarcinoma cells (MCF-7) which to be 1.5 times higher than the activity of the used reference anticancer drug tamoxifen (IC50 = 25.0 μM). A flexible receptor molecular docking simulation showed that the cytotoxicity of the synthesized conjugates of N-acetyl-d-glucosamine with α-aminophosphonates against breast adenocarcinoma MCF-7 cell line is due to their ability to inhibit EGFR kinase domain. In addition, it was found that conjugates 22a and 22b demonstrated antioxidant activity that was not typical for α-aminophosphonates.

ANTIOXIDANT AND ANTIBACTERIAL ACTIVITIES OF ETHYL ACETATE EXTRACT OF ACTINOMYCETES ISOLATED FROM TERMITE NESTS

Actinomycetes are an important source for the discovery of bioactive secondary metabolite compounds. Over 10,000 bioactive metabolite compounds have been isolated from terrestrial actinomycetes with various biological activities, such as antibiotic, antiviral, anti-inflammatory, antitumor, anticancer, and antioxidant. One source of origin for actinomycetes is soil, including termite nests. Utilization of natural sources such as actinomycetes from termite nests as antioxidants and antibacterials can be an alternative source of production of new secondary metabolite compounds. This research aims to evaluate the antioxidant and antibacterial activities of actinomycete extracts from termite nests. Antioxidant activity using the DPPH free radical scavenging method, and antibacterial activity against S. aureus. Antioxidant and antibacterial activity were performed by using the TLC dot-blot, TLC bioautography, and microdilution methods to determine the inhibitory concentration of 50% (IC50), antioxidant activity index (AAI), and minimum inhibitory concentration (MIC). From the 33 extracts tested, 16 extracts showed antioxidant activity with IC50 values range of 76.64-126.22 µg/mL or AAI value > 0.05 (moderate), and 8 extracts had moderate antibacterial activity against S. aureus (MIC values range of 256-512 µg/mL). Future research for scaling-up of actinomycete culture, isolating of active compounds, determining of the chemical structure of active compounds, and further testing as antioxidants and antibacterials still need to be carried out.

Rakicidin J and K, two cytotoxic and antibacterial cyclic depsipeptides from the marine bacterium Micromonospora chalcea

Rakicidin J (1) and rakicidin K (2), two new cyclic depsipeptides, were isolated from culture broth of Micromonospora chalcea FIM-R150103. Their structures were elucidated by extensive analysis of NMR, HR-ESI-MS, and electronic circular dichroism (ECD) data. The two compounds showed strong cytotoxic activity against human colon carcinoma HCT-8 and human pancreatic cancer PANC-1 cells under normoxic and hypoxic conditions in the range of IC50 values from 0.024 to 0.79 μg/mL. Moreover, compounds 1 and 2 also showed moderate antibacterial activity against ten Gram-positive bacterial strains with MIC values ranging from 4 to more than 32 μg/mL. Structure–activity relationship of these two compounds with a close analogue, rakicidin B1, is also discussed.

Exploring pyrrolidinyl-spirooxindole natural products as promising platforms for the synthesis of novel spirooxindoles as EGFR/CDK2 inhibitors for halting breast cancer cells.

Cancer represents a global challenge, and the pursuit of developing new cancer treatments that are potent, safe, less prone to drug resistance, and associated with fewer side effects poses a significant challenge in cancer research and drug discovery. Drawing inspiration from pyrrolidinyl-spirooxindole natural products, a novel series of spirooxindoles has been synthesized through a one-pot three-component reaction, involving a [3 + 2] cycloaddition reaction. The cytotoxicity against breast cancer cells (MCF-7 and MDA-MB-231) and safety profile against WISH cells of the newly developed library were assessed using the MTT assay. Compounds 5l and 5o exhibited notable cytotoxicity against MCF-7 cells (IC50 = 3.4 and 4.12μM, respectively) and MDA-MB-231 cells (IC50 = 8.45 and 4.32μM, respectively) compared to Erlotinib. Conversely, compounds 5a-f displayed promising cytotoxicity against MCF-7 cells with IC50 values range (IC50 = 5.87-18.5μM) with selective activity against MDA-MB-231 cancer cells. Compound 5g demonstrated the highest cytotoxicity (IC50 = 2.8μM) among the tested compounds. Additionally, compounds 5g, 5l, and 5n were found to be safe (non-cytotoxic) against WISH cells with higher IC50 values ranging from 39.33 to 47.2μM. Compounds 5g, 5l, and 5n underwent testing for their inhibitory effects against EGFR and CDK-2. Remarkably, they demonstrated potent EGFR inhibition, with IC50 values of 0.026, 0.067, and 0.04μM and inhibition percentages of 92.6%, 89.8%, and 91.2%, respectively, when compared to Erlotinib (IC50 = 0.03 μM, 95.4%). Furthermore, these compounds exhibited potent CDK-2 inhibition, with IC50 values of 0.301, 0.345, and 0.557μM and inhibition percentages of 91.9%, 89.4%, and 88.7%, respectively, in contrast to Roscovitine (IC50 = 0.556 μM, 92.1%). RT-PCR analysis was performed on both untreated and 5g-treated MCF-7 cells to confirm apoptotic cell death. Treatment with 5g increased the gene expression of pro-apoptotic genes P53, Bax, caspases 3, 8, and 9 with notable fold changes while decreasing the expression of the anti-apoptotic gene Bcl-2. Molecular docking and dynamic simulations (100 ns simulation using AMBER22) were conducted to investigate the binding mode of the most potent candidates, namely, 5g, 5l, and 5n, within the active sites of EGFR and CDK-2.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

Multifaceted bioactivity of thiosemicarbazide derivatives: Synthesis, characterization, and DFT investigations on inhibition of α-amylase, hydroxyl radical scavenging, and iron chelating activities with molecular docking insights

In this study, eight bioactive thiosemicarbazide derivatives (3a-h) were synthesized and characterized through 1HNMR , 13CNMR and Mass spectroscopic techniques. Finally, their inhibition activities against α-amylase and antioxidant activity were investigated. Among the synthetic series, five compounds 3 g (IC50 = 8.61 ± 1.42 µM) 3a (IC50 = 13.41 ± 1.65 µM), 3e (IC50 = 15.23 ± 1.17 µM), 3 h (IC50 = 17.37 ± 0.87 µM) and 3d (IC50 = 17.95 ± 1.99 µM) showed excellent inhibition by comparing with standard (acarbose, IC50 = 21.55 ± 1.31 µM). Similarly, in the case of iron chelating agent activity, product compounds 3a-h presented outstanding activity in the range of IC50 = 18.19 ± 1.81 to 63.42 ± 1.45 µM superior than standard (EDTA, IC50 = 66.43 ± 1.07 µM) while in hydroxyl radical scavenging activity all the synthesized products 3a-h also showed excellent scavenging activity in the range of IC50 values 25.85 ± 1.13 to 58.9 ± 2.95 µM when compared to standard vitamin C (IC50 = 60.51 ± 1.02 µM). We expanded our investigation to molecular interactions via a docking study, where these compounds were docked with the target protein to unveil their binding affinities and key interactions, offering additional insights into their inhibitory mechanisms. The chemical nature of the synthesized compounds was revealed through density functional theory (DFT) calculations at B3LYP/6–311++G(d,p). Intramolecular hydrogen bonding was explored using DFT-d3 and reduced density gradient (RDG) analysis. Additionally, various reactivity parameters were investigated through TD-DFT at the CAM-B3LYP/6–311++G(d,p) method.

Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy

The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of the series with an IC50 value range as low as 3–5 μM. Notably, RUSCO-2 was found to be highly cytotoxic in TNBC cell lines, suggesting a mode of action independent of the receptor status of the cells. As a proof of concept and taking advantage of the luminescent properties of one of the complexes obtained, uptake was monitored in human breast cancer MCF7 cell lines by fluorescence lifetime imaging microscopy (FLIM) to reveal that the compound is evenly distributed in the cytoplasm and that the incorporation of the heteroscorpionate ligand protects it from aqueous processes, conversion in another entity, or the loss of the chloride group. Finally, ROS studies were conducted, lipophilicity was estimated, the chloride/water exchange was studied, and stability studies in simulated biological media were carried out to propose structure-activity relationships.

Green synthesis of gold and silver nanoparticles using crude extract of Aconitum violaceum and evaluation of their antibacterial, antioxidant and photocatalytic activities.

Green synthesis of metal nanoparticles (NPs) has received extensive attention over other conventional approaches due to their non-toxic nature and more biocompatibility. Herein we report gold and silver NPs (AuNPs@AV and AgNPs@AV) prepared by employing a green approach using crude extract of Aconitum violaceum Jacquem. ex Stapf. The synthesized NPs were characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX), X-ray Diffraction (XRD), UV/Visible spectroscopy, Fourier Transform Infrared (FTIR), X-ray Photoelectron Spectroscopy (XPS), and Zeta Potential. Morphological analysis showed spherical and triangular shapes of the NPs with average size of <100nm. The AuNPs@AV and AgNPs@AV exhibited effective antibacterial activities, with minimum inhibitory concentrations (MICs) of 95 and 70μg/mL against Lactobacillus acidophilus (L. acidophilus) and 90 and 65μg/mL against Escherichia coli (E. coli), respectively. Strong antioxidant effect of AuNPs@AV and AgNPs@AV were reported against DPPH radical and PTIO within range of IC50 values; 161-80μg/ml as compared to the standard (23-11μg/mL) respectively. Moreover, the AuNPs@AV and AgNPs@AV showed efficient photocatalytic activity and degraded 89.88% and 93.7% methylene blue (MB) dye under UV light, respectively.

In vitro and in silico studies of alpha glucosidase inhibition and antifungal activity of coffea canephora husk.

The coffea canephora husk, a protected agricultural crop, is abundant in Vietnam. Examining the effects of C. canephora husk compounds on α-glucosidase and antifungal drug activity was the primary objective of this research. A cholestane-type steroid, coffeacanol A (1), was extracted from the ethyl acetate extract. Three cholestane-type derivatives (2-4) and three additional known compounds (5-7) were separated, and we used a variety of chromatographic techniques to identify a total of six substances. We used NMR to determine the chemical structures of these substances. Extensive HR-MS-ESI analysis and NMR experimental data were used to confirm the structure of the novel metabolite (1). The cholestane-type steroid was initially discovered in the Coffea canephora husk, marking the first instance in the coffee plant family to reveal chemical structures (1-7). The inhibition of α-glucosidase was found to be significantly higher in all compounds tested, with the exception of compounds (2) and (5). In vitro, the positive control showed the lowest inhibition, and the range of IC50 values was calculated to be 27.4 to 96.5 μM, which is lower than the IC50 value of 214.50 μM for the acarbose control. With an IC50 value of 27.4 μM, compound (7) showed the greatest capacity to inhibit α-glucosidase among the test compounds. The 3TOP and 2VF5 enzyme crystal structures were used for in silico docking investigations and validations of compounds (1-7). In silico calculations to explain how compound (7) shows high activity in vitro via the enzyme inhibition mechanism by residual amino acids, like Gly 1102 (B chain) and Glu 1095 (B chain), and their relative interaction with compounds (7) and acarbose. Compound (7) exhibited the best antifungal activity against Candida albicans fungus among three fungi, namely Candida albicans, Trichophyton mentagrophytes, and Trichophyton rubrum, with a MIC value of 25 μM. Compound (7) and fluconazole combined to form similar interactions in the contact ligand model, including the functional group, capping group, and linker part, which interacted fully with the 2VF5 enzyme, leading to effective in vitro inhibition.

Cobalt complexes of pyridine carboxaldehyde Schiff bases as cholinesterase inhibitors and anti-proliferative activity

Novel cobalt complexes of pyridine carboxaldehyde were meticulously designed, synthesized, and subsequently screened to assess their broad spectrum of biological potential. Pyridine carboxaldehyde semicarbazone, thiosemicarbazone, and cobalt chloride served as the initial materials, which were subjected to ultrasonication for the synthesis of the cobalt complexes. Characterization of the obtained compounds was conducted using FTIR, 1 H-NMR, elemental analysis, and both in-silico and in-vitro assessments were performed to evaluate their cholinesterase inhibition and anti-proliferative properties. It was found that all synthesized molecules selectively inhibited acetylcholinesterase within a range of IC50 values from 0.97±0.02 to 6.47±0.71 µM. Notably, CoRx-1Cl2 exhibited non-selective inhibition against both acetylcholinesterase and butyrylcholinesterase, with IC50 values of 1.91±0.08 and 12.97±2.46 µM, respectively. Subsequent MTT assays and cytotoxic studies were carried out on U-87 and HEK-293 cell lines, revealing that all synthesized compounds were non-toxic to the normal cell line HEK-293. Conversely, cell viability in U-87 cells ranged from 20.93% to 92.9%. These findings suggest that the synthesized cobalt complexes possess a multi-targeting effect and hold potential for use in the management of conditions such as Glioblastoma and Alzheimer’s diseases.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61±0.15to 43.72±1.18μM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzymeoffers promising prospects for future research in the field of neuropharmacology.