Bioactive Polyketide and Diketopiperazine Derivatives from the Mangrove-Sediment-Derived Fungus Aspergillus sp. SCSIO41407

Ten polyketide derivatives (1–10), including a new natural product named (E)-2,4-dihydroxy-3-methyl-6-(2-oxopent-3-en-1-yl) benzaldehyde (1), and five known diketopiperazines (11–15), were isolated from the mangrove-sediment-derived fungus Aspergillus sp. SCSIO41407. The structures of 1–15 were determined via NMR and MS spectroscopic analysis. In a variety of bioactivity screening, 3 showed weak cytotoxicity against the A549 cell line, and 2 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 3, 5, and 6 showed inhibition against acetylcholinesterase (AChE) with IC₅₀ values of 23.9, 39.9, and 18.6 μM. Compounds 11, 12, and 14 exhibited obvious inhibitory activities of lipopolysaccharide (LPS)-induced nuclear factor-κB (NF-κB) with IC₅₀ values of 19.2, 20.9, and 8.7 μM, and they also suppressed RANKL-induced osteoclast differentiation in bone marrow macrophages cells (BMMCs), with the concentration of 5 μM. In silico molecular docking with AChE and NF-κB p65 protein were also performed to understand the inhibitory activities, and 1, 11–14 showed obvious protein/ligand-binding effects to the NF-κB p65 protein.     

Secondary Metabolites from Hericium erinaceus and Their Anti-Inflammatory Activities

Hericium erinaceus, a culinary and medicinal mushroom, is widely consumed in Asian countries. Chemical investigation on the fruiting bodies of Hericium erinaceus led to the isolation of one new ergostane-type sterol fatty acid ester, erinarol K (1); and eleven known compounds: 5α,8α -epidioxyergosta-6,22-dien-3β-yl linoleate (2); ethyl linoleate (3); linoleic acid (4); hericene A (5); hericene D (6); hericene E (7); ergosta-4,6,8(14),22-tetraen-3-one (8); hericenone F (9); ergosterol (10); ergosterol peroxide (11); 3β,5α,6α,22E-ergosta-7,22-diene-3,5,6-triol 6-oleate (12). The chemical structures of the compounds were determined by 1D and 2D NMR (nuclear magnetic resonance) spectroscopy, mass spectra, etc. Anti-inflammatory effects of the isolated aromatic compounds (5–7, 9) were evaluated in terms of inhibition of pro-inflammatory mediator (TNF-α, IL-6 and NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. The results showed that compounds 5 and 9 exhibited moderate activity against TNF-α (IC₅₀: 78.50 μM and 62.46 μM), IL-6 (IC₅₀: 56.33 μM and 48.50 μM) and NO (IC₅₀: 87.31 μM and 76.16 μM) secretion. These results supply new information about the secondary metabolites of Hericium erinaceus and their anti-inflammatory effects.     

Asperflaloids A and B from Aspergillus flavipes DZ-3, an Endophytic Fungus of Eucommia ulmoides Oliver

The fungus strain DZ-3 was isolated from twigs of the well-known medicinal plant Eucommia ulmoides Oliver and identified as Aspergillus flavipes. Two new alkaloids, named asperflaloids A and B (1 and 2), together with 10 known compounds (3–12) were obtained from the EtOAc extract of the strain. Interestingly, the alkaloids 1–4 with different frameworks are characterized by the presence of the same anthranilic acid residue. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of asperflaloids A and B was resolved by quantum chemistry calculation. All compounds were screened for their inhibitions against α-glucosidase and the antioxidant capacities. The results were that compound 3 had an IC₅₀ value of 750.8 μM toward α-glucosidase, and the phenol compounds 7 and 8 exhibited potent antioxidant capacities with IC₅₀ values 14.4 and 27.1 μM respectively.     

Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer’s Disease Potential

Marine alkaloids belonging to the lamellarins family, which incorporate a 5,6-dihydro-1-phenylpyrrolo[2,1-a]isoquinoline (DHPPIQ) moiety, possess various biological activities, spanning from antiviral and antibiotic activities to cytotoxicity against tumor cells and the reversal of multidrug resistance. Expanding a series of previously reported imino adducts of DHPPIQ 2-carbaldehyde, novel aliphatic and aromatic Schiff bases were synthesized and evaluated herein for their cytotoxicity in five diverse tumor cell lines. Most of the newly synthesized compounds were found noncytotoxic in the low micromolar range (<30 μM). Based on a Multi-fingerprint Similarity Search aLgorithm (MuSSeL), mainly conceived for making protein drug target prediction, some DHPPIQ derivatives, especially bis-DHPPIQ Schiff bases linked by a phenylene bridge, were prioritized as potential hits addressing Alzheimer’s disease-related target proteins, such as cholinesterases (ChEs) and monoamine oxidases (MAOs). In agreement with MuSSeL predictions, homobivalent para-phenylene DHPPIQ Schiff base 14 exhibited a noncompetitive/mixed inhibition of human acetylcholinesterase (AChE) with K_i in the low micromolar range (4.69 μM). Interestingly, besides a certain inhibition of MAO A (50% inhibition of the cell population growth (IC₅₀) = 12 μM), the bis-DHPPIQ 14 showed a good inhibitory activity on self-induced β-amyloid (Aβ)_1–40 aggregation (IC₅₀ = 13 μM), which resulted 3.5-fold stronger than the respective mono-DHPPIQ Schiff base 9.     

Cinnamides Target Leishmania amazonensis Arginase Selectively

Caffeic acid and related natural compounds were previously described as Leishmania amazonensis arginase (L-ARG) inhibitors, and against the whole parasite in vitro. In this study, we tested cinnamides that were previously synthesized to target human arginase. The compound caffeic acid phenethyl amide (CAPA), a weak inhibitor of human arginase (IC₅₀ = 60.3 ± 7.8 μM) was found to have 9-fold more potency against L-ARG (IC₅₀ = 6.9 ± 0.7 μM). The other compounds that did not inhibit human arginase were characterized as L-ARG, showing an IC₅₀ between 1.3–17.8 μM, and where the most active was compound 15 (IC₅₀ = 1.3 ± 0.1 μM). All compounds were also tested against L. amazonensis promastigotes, and only the compound CAPA showed an inhibitory activity (IC₅₀ = 80 μM). In addition, in an attempt to gain an insight into the mechanism of competitive L-ARG inhibitors, and their selectivity over mammalian enzymes, we performed an extensive computational investigation, to provide the basis for the selective inhibition of L-ARG for this series of compounds. In conclusion, our results indicated that the compounds based on cinnamoyl or 3,4-hydroxy cinnamoyl moiety could be a promising starting point for the design of potential antileishmanial drugs based on selective L-ARG inhibitors.     

Secondary Metabolites with Anti-Inflammatory Activities from an Actinobacteria Herbidospora daliensis

Bioassay-guided fractionation of extracts derived from solid cultures of a Herbidospora daliensis originating from Taiwan led to the isolation of five new compounds, for which we propose the name herbidosporadalins A–E (1–5), one isolated for the first time, herbidosporadalin F (6), together with two known compounds (7 & 8). Their structures were elucidated by spectroscopic analyses, including 1D- and 2D-NMR experiments with those of known analogues, and on the basis of HR-EI-MS mass spectrometry, their anti-inflammatory activities were also evaluated. Of these isolates, herbidosporadalin A (1), B (2), F (6) and G (8) showed NO inhibitory activity, with IC₅₀ values of 11.8 ± 0.9, 7.1 ± 2.9, 17.8 ± 1.7, and 13.3 ± 6.5 μM, stronger than the positive control quercetin (IC₅₀ = 36.8 ± 1.3 μM). To the best of our knowledge, this is the first report on 3,4-seco-friedelane metabolites (5, 6 & 8) from the genus Herbidospora.     

Pentacyclic Triterpenoids from Sabia discolor Dunn and Their α-Glycosidase Inhibitory Activities

Four new pentacyclic triterpenoids named Sabiadiscolor A–D (1 and 7–9) together with eleven known ones were isolated by repeated column chromatography. Their structures were identified and characterized by NMR and MS spectral data as 6 oleanane-type pentacyclic triterpenoids (1–6), 7 ursane-type ones (7–13), and 2 lupanane-type ones (14–15). Except for compound 15, all other compounds were isolated from Sabia discolor Dunn for the first time. Their α-glycosidase inhibitory activities were evaluated, which showed that compounds 1, 3, 8, 9, 13, and 15 implied remarkable activities with IC₅₀ values ranging from 0.09 to 0.27 μM, and the preliminary structure–activity relationship was discussed.     

Salvia officinalis L. from Italy: A Comparative Chemical and Biological Study of Its Essential Oil in the Mediterranean Context

Salvia officinalis L. (sage) is one of the most appreciated plants for its plethora of biologically active compounds. The objective of our research was a comparative study, in the Mediterranean context, of chemical composition, anticholinesterases, and antioxidant properties of essential oils (EOs) from sage collected in three areas (S1–S3) of Southern Italy. EOs were extracted by hydrodistillation and analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory properties were investigated by employing Ellman’s method. Four in vitro assays, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric-reducing ability power (FRAP), and β-carotene bleaching tests, were used to study the antioxidant effects. Camphor (16.16–18.92%), 1,8-cineole (8.80–9.86%), β-pinene (3.08–9.14%), camphene (6.27–8.08%), and α-thujone (1.17–9.26%) are identified as the most abundant constituents. However, the content of these constituents varied depending on environmental factors and pedoclimatic conditions. Principal component analysis (PCA) was performed. Based on Relative Antioxidant Capacity Index (RACI), S2 essential oil exhibited the highest radical potential with an IC₅₀ value of 20.64 μg/mL in ABTS test and presented the highest protection of lipid peroxidation with IC₅₀ values of 38.06 and 46.32 μg/mL after 30 and 60 min of incubation, respectively. The most promising inhibitory activity against BChE was found for S3 sample (IC₅₀ of 33.13 μg/mL).     

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis,In Vitro α-Amylase Inhibitory Activity,Molecular Docking and Structure–Activity Relationship Analysis

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by ¹H NMR, ¹³C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 μM, and with IC₅₀ values of 12.6 ± 0.2 μM–27.6 ± 1.1 μM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 μM), with a potency (IC₅₀ = 12.6 ± 0.2 μM) similar to that of the positive control acarbose (IC₅₀ = 12.4 ± 0.1 μM). The study of the structure–activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.     

Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202

Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3–11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC₅₀ value of 1.31 μM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC₅₀ value of 2.32 μM.     

Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a–8i and 9a–9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC₅₀ = 0.047 ± 0.006 μM) and selective antiproliferative effects against H1975 (IC₅₀ = 0.044 ± 0.011 μM) and A431 cells (IC₅₀ = 0.119 ± 0.036 μM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.     

Improved Synthesis of Asymmetric Curcuminoids and Their Assessment as Antioxidants

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon’s method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n-BuNH₂ in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41–76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b, 9d, 9e, 9f, 9g, 9h, 9i, 9j, and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC₅₀ = 37.57 ± 0.89 μM) and 9e (IC₅₀ = 37.17 ± 1.76 μM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC₅₀ = 11.36 ± 0.65 μM) and 9i (IC₅₀ = 10.91 ± 0.77 μM) displayed potent 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC₅₀ = 10.14 ± 1.04 μM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.     

Dianthiamides A–E,Proline-Containing Orbitides from Dianthus chinensis

Orbitides are plant-derived small cyclic peptides with a wide range of biological activities. Phytochemical investigation of the whole plants of Dianthus chinensis was performed with the aim to discover new bioactive orbitides. Five undescribed proline-containing orbitides, dianthiamides A–E (1–5), were isolated from a methanolic extract of Dianthus chinensis. Their structures were elucidated by extensive analysis of 1D and 2D NMR and HRESI–TOF–MS as well as ESI–MS/MS fragmentation data. The absolute configuration of the amino acid residues of compounds 1–5 was determined by Marfey’s method. All compounds were tested for their cytotoxic activity, and dianthiamide A (1) exhibited weak activity against A549 cell line with IC₅₀ value of 47.9 μM.     

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC₅₀ = 66.4 μM in HepG2 cells, IC₅₀ = 43.1 μM in HepG2 cells) at 10 μM.     

Photophysical Study and Biological Applications of Synthetic Chalcone-Based Fluorescent Dyes

A chalcone series (3a–f) with electron push–pull effect was synthesized via a one-pot Claisen–Schmidt reaction with a simple purification step. The compounds exhibited strong emission, peaking around 512–567 nm with mega-stokes shift (∆λ = 93–139 nm) in polar solvents (DMSO, MeOH, and PBS) and showed good photo-stability. Therefore, 3a–f were applied in cellular imaging. After 3 h of incubation, green fluorescence was clearly brighter in cancer cells (HepG2) compared to normal cells (HEK-293), suggesting preferential accumulation in cancer cells. Moreover, all compounds exhibited higher cytotoxicity within 24 h toward cancer cells (IC₅₀ values ranging from 45 to 100 μM) than normal cells (IC₅₀ value >100 μM). Furthermore, the antimicrobial properties of chalcones 3a–f were investigated. Interestingly, 3a–f exhibited antibacterial activities against Escherichia coli and Staphylococcus aureus, with minimum bactericidal concentrations (MBC) of 0.10–0.60 mg/mL (375–1000 µM), suggesting their potential antibacterial activity against both Gram-negative and Gram-positive bacteria. Thus, this series of chalcone-derived fluorescent dyes with facile synthesis shows great potential for the development of antibiotics and cancer cell staining agents.     

Bioactive Abietane-Type Diterpenoid Glycosides from Leaves of Clerodendrum infortunatum (Lamiaceae)

In this study, two previously undescribed diterpenoids, (5R,10S,16R)-11,16,19-trihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-3,8,11,13-abietatetraene-7-one (1) and (5R,10S,16R)-11,16-dihydroxy-12-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl-17(15→16),18(4→3)-diabeo-4-carboxy-3,8,11,13-abietatetraene-7-one (2), and one known compound, the C₁₃-nor-isoprenoid glycoside byzantionoside B (3), were isolated from the leaves of Clerodendrum infortunatum L. (Lamiaceae). Structures were established based on spectroscopic and spectrometric data and by comparison with literature data. The three terpenoids, along with five phenylpropanoids: 6′-O-caffeoyl-12-glucopyranosyloxyjasmonic acid (4), jionoside C (5), jionoside D (6), brachynoside (7), and incanoside C (8), previously isolated from the same source, were tested for their in vitro antidiabetic (α-amylase and α-glucosidase), anticancer (Hs578T and MDA-MB-231), and anticholinesterase activities. In an in vitro test against carbohydrate digestion enzymes, compound 6 showed the most potent effect against mammalian α-amylase (IC₅₀ 3.4 ± 0.2 μM) compared to the reference standard acarbose (IC₅₀ 5.9 ± 0.1 μM). As yeast α-glucosidase inhibitors, compounds 1, 2, 5, and 6 displayed moderate inhibitory activities, ranging from 24.6 to 96.0 μM, compared to acarbose (IC₅₀ 665 ± 42 μM). All of the tested compounds demonstrated negligible anticholinesterase effects. In an anticancer test, compounds 3 and 5 exhibited moderate antiproliferative properties with IC₅₀ of 94.7 ± 1.3 and 85.3 ± 2.4 μM, respectively, against Hs578T cell, while the rest of the compounds did not show significant activity (IC₅₀ > 100 μM).     

Bio-Guided Fractionation of Stem Bark Extracts from Phyllanthus muellarianus: Identification of Phytocomponents with Anti-Cholinesterase Activity

A combination of flash chromatography, solid phase extraction, high-performance liquid chromatography, and in vitro bioassays was used to isolate phytocomponents endowed with anticholinesterase activity in extract from Phyllanthus muellarianus. Phytocomponents responsible for the anti-cholinesterase activity of subfractions PMF1 and PMF4 were identified and re-assayed to confirm their activity. Magnoflorine was identified as an active phytocomponent from PMF1 while nitidine was isolated from PMF4. Magnoflorine was shown to be a selective inhibitor of human butyrylcholinesterase—hBChE (IC₅₀ = 131 ± 9 μM and IC₅₀ = 1120 ± 83 μM, for hBuChE and human acetylcholinesterase—hAChE, respectively), while nitidine showed comparable inhibitory potencies against both enzymes (IC₅₀ = 6.68 ± 0.13 μM and IC₅₀ = 5.31 ± 0.50 μM, for hBChE and hAChE, respectively). When compared with the commercial anti-Alzheimer drug galanthamine, nitidine was as potent as galanthamine against hAChE and one order of magnitude more potent against hBuChE. Furthermore, nitidine also showed significant, although weak, antiaggregating activity towards amyloid-β self-aggregation.     

Discovery of Amide-Functionalized Benzimidazolium Salts as Potent α-Glucosidase Inhibitors

α-Glucosidase inhibitors (AGIs) are used as medicines for the treatment of diabetes mellitus. The α-Glucosidase enzyme is present in the small intestine and is responsible for the breakdown of carbohydrates into sugars. The process results in an increase in blood sugar levels. AGIs slow down the digestion of carbohydrates that is helpful in controlling the sugar levels in the blood after meals. Among heterocyclic compounds, benzimidazole moiety is recognized as a potent bioactive scaffold for its wide range of biologically active derivatives. The aim of this study is to explore the α-glucosidase inhibition ability of benzimidazolium salts. In this study, two novel series of benzimidazolium salts, i.e., 1-benzyl-3-{2-(substituted) amino-2-oxoethyl}-1H-benzo[d]imidazol-3-ium bromide 9a–m and 1-benzyl-3-{2-substituted) amino-2-oxoethyl}-2-methyl-1H-benzo[d] imidazol-3-ium bromide 10a–m were screened for their in vitro α-glucosidase inhibitory potential. These compounds were synthesized through a multistep procedure and were characterized by ¹H-NMR, ¹³C-NMR, and EI-MS techniques. Compound 10d was identified as the potent α-glucosidase inhibitor among the series with an IC₅₀ value of 14 ± 0.013 μM, which is 4-fold higher than the standard drug, acarbose. In addition, compounds 10a, 10e, 10h, 10g, 10k, 10l, and 10m also exhibited pronounced potential for α-glucosidase inhibition with IC₅₀ value ranging from 15 ± 0.037 to 32.27 ± 0.050 µM when compared with the reference drug acarbose (IC₅₀ = 58.8 ± 0.12 μM). A molecular docking study was performed to rationalize the binding interactions of potent inhibitors with the active site of the α-glucosidase enzyme.     

Synthesis and Biological Activity Evaluation of Coumarin-3-Carboxamide Derivatives

A series of novel coumarin-3-carboxamide derivatives were designed and synthesized to evaluate their biological activities. The compounds showed little to no activity against gram-positive and gram-negative bacteria but specifically showed potential to inhibit the growth of cancer cells. In particular, among the tested compounds, 4-fluoro and 2,5-difluoro benzamide derivatives (14b and 14e, respectively) were found to be the most potent derivatives against HepG2 cancer cell lines (IC₅₀ = 2.62–4.85 μM) and HeLa cancer cell lines (IC₅₀ = 0.39–0.75 μM). The activities of these two compounds were comparable to that of the positive control doxorubicin; especially, 4-flurobenzamide derivative (14b) exhibited low cytotoxic activity against LLC-MK2 normal cell lines, with IC₅₀ more than 100 μM. The molecular docking study of the synthesized compounds revealed the binding to the active site of the CK2 enzyme, indicating that the presence of the benzamide functionality is an important feature for anticancer activity.     

Phenolic compounds,essential oil composition,and antioxidant activity of Angelica purpurascens (Avé-Lall.) Gill

In this study, methanol extracts (MEs) and essential oil (EO) of Angelica purpurascens (Avé-Lall.) Gill obtained from different parts (root, stem, leaf, and seed) were evaluated in terms of antioxidant activity, total phenolics, compositions of phenolic compound, and essential oil with the methods of 2,2-azino-bis(3ethylbenzo-thiazoline-6-sulfonic acid (ABTS•⁺), 2,2-diphenyl-1-picrylhydrazil (DPPH•) radical scavenging activities, and ferric reducing/antioxidant power (FRAP), the Folin–Ciocalteu, liquid chromatography−tandem mass spectrometry (LC−MS/MS), and gas chromatography-mass spectrometry (GC−MS), respectively. The root extract of A. purpurascens exhibited the highest ABTS•⁺, DPPH•, and FRAP activities (IC₅₀: 0.05 ± 0.0001 mg/mL, IC₅₀: 0.06 ± 0.002 mg/mL, 821.04 ± 15.96 µM TEAC (Trolox equivalent antioxidant capacity), respectively). Moreover, EO of A. purpurascens root displayed DPPH• scavenging activity (IC₅₀: 2.95 ± 0.084 mg/mL). The root extract had the highest total phenolic content (438.75 ± 16.39 GAE (gallic acid equivalent), µg/mL)). Twenty compounds were identified by LC−MS/MS. The most abundant phenolics were ferulic acid (244.39 ± 15.64 μg/g extract), benzoic acid (138.18 ± 8.84 μg/g extract), oleuropein (78.04 ± 4.99 μg/g extract), and rutin (31.21 ± 2.00 μg/g extract) in seed, stem, root, and leaf extracts, respectively. According to the GC−MS analysis, the major components were determined as α-bisabolol (22.93%), cubebol (14.39%), α-pinene (11.63%), and α-limonene (9.41%) among 29 compounds. Consequently, the MEs and EO of A. purpurascens can be used as a natural antioxidant source.