Synthesis,Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives with Substituted Amino Moiety

A series of novel quinazolinone derivatives containing a substituted amino moiety were synthesized, evaluated for their cytotoxic and antibacterial activities. The results of MTT assay showed that all synthesized target compounds 5A  –  5O showed potent cytotoxicity against SGC‐7901 (IC₅₀, 0.72 – 1.41 μm ). Moreover, the compounds 5D , 5I , and 5K showed better selectivity as compared with positive controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell line HUVSMC. Among synthesized compounds, the compounds 5E , 5J , 5L , and 5N showed broad‐spectrum cytotoxic activities against at least four cancer cell lines at a micromolar level. The results of antibacteria evaluation revealed that all synthesized compounds showed good to moderate antibacterial activities against Gram‐negative bacteria Escherichia coli. Among them, the MIC values of the compounds 5C , 5F , and 5M were 0.31 μg/mL.     

Copper Oxide Nanomaterials Derived from Zanthoxylum armatum DC. and Berberis lycium Royle Plant Species: Characterization,Assessment of Free Radical Scavenging and Antibacterial Activity

Copper oxide nanomaterials were synthesized by a facile sustainable biological method using two plant species (Zanthoxylum armatum DC. and Berberis lycium Royle ). The formation of materials was confirmed by FT‐IR, ATR, UV‐visible, XRD, TEM, SEM, EDX, TGA and PL. The antibacterial activity was evaluated by agar well diffusion method to ascertain the efficacy of plant species extract and extract derived copper oxide nanomaterials against six Gram‐positive bacteria namely Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Corynebacterium diphtheriae, Corynebacterium xerosis, Bacillus cereus and four Gram‐negative bacteria such as Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris against the standard drug, Ciprofloxacin for Gram‐positive and Gentamicin for Gram‐negative bacteria, respectively. In both cases, copper oxide nanomaterials were found to be sensitive in all the bacterial species. Sensitivity of copper oxide nanomaterials shows an be higher as compared to plant species extract against different bacteria. Scavenging activity of plant extracts along with nanomaterials have been accessed using previously reported protocols employing ascorbic acid as standard. Scavenging activity of copper oxide nanomaterials shows an increase with increase in concentration. The biological activity (bactericidal and scavenging efficiency) of plant derived copper oxide nanomaterials revealed that these materials can be used as potent antimicrobial agent and DPPH scavengers in industrial as well as pharmacological fields.     

New Phenylpropanoid Glycosides from Illicium majus and Their Radical Scavenging Activities

Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides ( 1 – 4 ) and one new phenolic glycoside ( 9 ), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl β-D-glucopyranoside ( 1 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-glucopyranoside ( 2 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-xylopyranoside ( 3 ), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-β-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate ( 4 ), and 4-(2-hydroxyethyl)phenyl 3-O-β-D-glucopyranosyl-β-D-glucopyranoside ( 9 ). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-β-D-glucopyranose ( 17 ) and soulieana acid 1 ( 18 ), exhibited moderate radical scavenging activities (IC₅₀=37.7±4.4 μM and IC₅₀=97.2±3.4 μM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 μg/mL).     

Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities

One new ent‐kaurane diterpenoid, 11β,16α‐dihydroxy‐ent‐kauran‐19‐oic acid ( 1 ), together with eight known analogues 2 – 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic diterpenoids, kaurenoic acid ( 3 ), was converted to seven derivatives, 10 – 16 . All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG‐2), and stomach (SGC‐7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 – 16 , with 15‐keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC₅₀ value ranging from 0.05 to 3.71 μm . Compounds 10 – 12 , with oxime on C(15) showed moderate inhibitory effects and compounds 1 – 9 showed no cytotoxicities on them. Structure–activity relationships were also discussed based on the experimental data obtained. The known derivative, 15‐oxokaurenoic acid 4‐piperdin‐1‐ylbutyl ester ( 17 ), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis‐inducing activity by flow‐cytometric analysis.     

New Acetophenone Derivatives from Acronychia oligophlebia and Their Anti‐inflammatory and Antioxidant Activities

Seven new acetophenone derivatives (acroliones A – G, 1  –  7 ) and three known ones ( 8  –  10 ) were isolated from the leaves of Acronychia oligophlebia. Their structures were elucidated based on extensive spectroscopic analyses (IR, UV, HR‐ESI‐MS, 1D‐ and 2D‐NMR), X‐ray diffraction and comparison with literature data. The anti‐inflammatory and antioxidant activities of all isolates were evaluated.     

Phloroglucinol Derivatives from the Fruits of Eucalyptus globulus and Their Cytotoxic Activities

A new phloroglucinol derivative, named eucalyptin B ( 1 ), along with five related known compounds ( 2 – 6 ), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D‐ and 2D‐NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds ( 1 – 6 ) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B ( 1 ) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B ( 1 ), the apoptosis factor proteins (Bcl2 and Bax) and caspase‐3 levels in A549 cells were also determined by Western‐blot analysis. By cytotoxic assay, eucalyptin B ( 1 ) exhibited potent cytotoxicity against A549 cells with an IC₅₀ value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B ( 1 ) inhibited 5‐fold and increased 10‐folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11‐fold increase in the level of caspase‐3 confirmed eucalyptin B ( 1 ) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B ( 1 ) has promising cytotoxic activity in tumor cells, especially in A549.     

Preparation of New Spiropyrazole,Pyrazole and Hydantoin Derivatives and Investigation of Their Antioxidant and Antibacterial Activities.

In this study, the synthesis of new spiropyrazoles, pyrazole and hydantoin heterocycles is reported by three component reactions of parabanic acids, hydrazine derivatives, and phenacyl bromides in the presence of triphenylphosphine as a nucleophile and triethylamine as a base in good to high yields (69–91 %). Evaluation of the synthesized compounds revealed a good to excellent antioxidant activities (37.6–96.2 %) using DPPH inhibitory potency. Among these compounds, hydantoin derivatives displayed higher antioxidant activities (93.7–96.2 %) comparing with spiropyrazoles and pyrazoles. The obtained results showed that Cl and Br substituents on the phenyl ring increased antioxidant activities of the related heterocycles. The antibacterial activities of the synthesized compounds were examined against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Among the synthesized heterocycles, 2-[1,3-dimethyl-2,5-dioxo-4-(2-oxo-2-phenylethyl)imidazolidin-4-yl]hydrazine-1-carbothioamide exhibited the excellent antibacterial activity against both Gram-positive and Gram-negative bacteria.     

Synthesis of Gibbilimbols A-D,Cytotoxic and Antibacterial Alkenylphenols Isolated from Piper gibbilimbum

Gibbilimbols A [(E)-4-(4-decenyl)phenol, 1], B [(E)-4-(3-decenyl)phenol, 2], C [(E)-4-(4-octenyl)phenol, 3] and D [(E)-4-(3-octenyl)phenol, 4] were synthesized by coupling the phenolic parts with the alkyne parts and then reducing the triple bond of the resulting alkynylphenols. These alkenylphenols (1?4) are the cytotoxic and antibacterial constituents of the leaves of a medicinal plant (Piper gibbilimbum) that is used as a traditional medicine in Papua New Guinea.     

Vibsane‐Type Diterpenoids from Viburnum odoratissimum and Their Cytotoxic and HSP90 Inhibitory Activities

Four new vibsane‐type diterpenoids, vibsanol I ( 1 ), 15‐hydroperoxyvibsanol A ( 2 ), 14‐hydroperoxyvibsanol B ( 3 ), 15‐O‐methylvibsanin U ( 4 ), and a new natural product, 5,6‐dihydrovibsanin B ( 5 ), as well as six known analogues, were isolated from the twigs and leaves of Viburnum odoratissimum. Their structures were elucidated by spectroscopic analyses and chemical derivatization method. All compounds showed different levels of cytotoxicity against five cell lines (HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480). Remarkably, 14,18‐O‐diacetyl‐15‐O‐methylvibsanin U ( 4a ) showed significant cytotoxicity against HL‐60, A‐549, SMMC‐7721, MCF‐7, and SW480, with IC₅₀ values of 0.15 ± 0.01, 0.69 ± 0.01, 0.41 ± 0.02, 0.75 ± 0.03, and 0.48 ± 0.03 μm , respectively. In addition, vibsanin K ( 10 ) was identified as a HSP90 inhibitor with an IC₅₀ value of 19.16 μm .     

Phloroglucinol Derivatives from Myrtus communis ‘Variegata’ and Their Antibacterial Activities

Myrtucomvalones D–F, three new triketone‐phloroglucinol‐triketone adducts, and three known ones (myrtucommulone E, myrtucommulone D and callistenone D) were obtained from Myrtus communis ‘Variegata’. Myrtucomvalone D is a pair of enantiomers which was further resolved into (+)‐myrtucomvalone D and (?)‐myrtucomvalone D by chiral HPLC. Their structures and complete stereochemistry were established from interpretation of NMR and crystallographic data and chemical calculations. Myrtucomvalone F, myrtucommulone D and callistenone D showed significant antibacterial activities.     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Diarylheptanoids from Acer nikoense Bark and Their Derivatives

Nine cyclic diarylheptanoids, 1 – 9 , including two new compounds, i.e., 9‐oxoacerogenin A ( 8 ) and 9‐O‐β‐D ‐glucopyranosylacerogenin K ( 9 ), along with three acyclic diarylheptanoids, 10 – 12 , and four phenolic compounds, 13 – 16 , were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K ( 17 ) and D ‐glucose. Two of the cyclic diarylheptanoids, acerogenin A ( 1 ) and (R)‐acerogenin B ( 5 ), were converted to their ether and ester derivatives, 18 – 24 and 27 – 33 , respectively, and to the dehydrated derivatives, 25, 26, 34 , and 35 . Upon evaluation of compounds 1 – 16 and 18 – 35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2 – 4, 6, 9 , and 12 , and two phenolic glycosides, 15 and 16 , exhibited inhibitory activities with 24–61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88–106% of cell viability at 100 μM ). In addition, when compounds 1 – 16 and 18 – 35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11 , ten ether and ester derivatives, 18 – 22 and 27 – 31 , and two dehydrated derivatives, 34 and 35 , exhibited potent cytotoxicities against HL60 human leukemia cell line (IC₅₀ 8.1–19.3 μM ), and five compounds, 10, 11, 20, 29 , and 30 , against CRL1579 human melanoma cell line (IC₅₀ 10.1–18.4 μM ).     

Antioxidant,Cytotoxic and Antimicrobial Activity of Chitosan Preparations Extracted from Ganoderma Lucidum Mushroom

Two chitosan extracts were prepared by chemical and enzymatic treatment of Ganoderma lucidum mushroom, as an alternative source to crustacean shells. The molecular weight of the enzymatic extract was lower than that of the chemical one and of shrimp chitosan, as determined by viscosity measurements. Characteristic signals were identified in the ¹H‐NMR spectra and high deacetylation degree indicated good physico‐chemical properties for both mushroom chitosan extracts. The scavenging capacity of mushroom chitosan extracts was moderate against the synthetic radicals of 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH), but higher values were observed for the enzymatic extract, compared to the chemical extract and shrimp chitosan. In vitro cytotoxicity was evaluated in L929 mouse fibroblast cell lines and the results of MTT assay showed good cytocompatibility in the tested range of concentrations. The growth of Gram‐positive bacteria was inhibited more than Gram‐negative bacteria in the presence of mushroom chitosan extracts, in particular by the chemical one, indicating their efficiency as antimicrobial agents. All these results strengthen the evidence of mushroom polysaccharide preparations availability for biomedical applications.     

Phenolic Compounds from the Fruits of Prunus davidiana (Rosaceae) and Their Antioxidant Activities

This research was supported by Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ014204032019) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1A6A3A01100042).     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Limonoids,Alkaloids, and Phenolic Compounds from Phellodendron amurense Bark

Four limonoids, 1  –  4 , five alkaloids, 5  –  9 , and four phenolic compounds, 10  –  13 , were isolated from a MeOH extract of the bark of Phellodendron amurense (Rutaceae). Among these, compound 13 was new, and its structure was established as rel‐(1R,2R,3R)‐5‐hydroxy‐3‐(4‐hydroxy‐3‐methoxyphenyl)‐6‐methoxy‐1‐(methoxycarbonylmethyl)indane‐2‐carboxylic acid methyl ester (γ‐di(methyl ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1  –  13 against the melanogenesis in the B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), four compounds, limonin ( 1 ), noroxyhydrastinine ( 6 ), haplopine ( 7 ), and 4‐methoxy‐1‐methylquinolin‐2(1H)‐one ( 8 ), exhibited potent melanogenesis‐inhibitory activities with almost no toxicity to the cells. Western blot analysis revealed that compound 6 inhibited melanogenesis, at least in part, by inhibiting the expression of protein levels of tyrosinase, TRP‐1, and TRP‐2 in α‐MSH‐stimulated B16 melanoma cells. In addition, when compounds 1  –  13 were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK‐BR‐3) cancer cell lines, five compounds, berberine ( 5 ), 8 , canthin‐6‐one ( 9 ), α‐di‐(methyl ferulate) ( 12 ), and 13 , exhibited cytotoxicities against one or more cancer cell lines with IC₅₀ values in the range of 2.6 – 90.0 μm . In particular, compound 5 exhibited strong cytotoxicity against AZ521 (IC₅₀ 2.6 μm ) which was superior to that of the reference cisplatin (IC₅₀ 9.5 μm ).     

Phenolic Profiling,Antioxidant, and Antibacterial Activities of Selected Medicinal Plants from Tunisia

Phytochemical screening of aqueous extract from six medicinal wild plants grown in South-eastern of Tunisia: Atriplex halimus, Teucrium polium, Moricandia arvensis, Deverra tortuoa, Haplophyllum tuberculatum and Polygonum equisetiforme were evaluated. Both decoction and ultrasound assisted extraction were used. Antioxidant, antibacterial proprieties, and phenolic profiling, using LC-ESI-MS method, were assessed. Total polyphenols, flavonoids, and condensed tannins contents ranged from 7.47±0.19 to 22.25±0.49 mg GAE/g Dw, 5.47±0.06 to 7.55±0.07 mg RE/g Dw, and 0.33±0.02 to 19.43±0.64 mg TAE/g Dw, respectively. Moreover, the reducing power and DPPH tests showed that P. equisetiforme (EC₅₀: 12.50±0.50 μg/ml; DPPH⋅⁺: 213.49±4.24 mg TEAC/g DW), T. polium (EC₅₀: 25.00±1.00 μg/ml; DPPH⋅⁺: 181.39±9.47 mg TEAC/g DW) as well as H. tuberculatum (EC₅₀: 56.25±0.25 μg/ml; DPPH⋅⁺: 177.83±5.85 mg TEAC/g DW) extracts were the most effective natural antioxidants. For anti-bacterial activity, the ultrasonic extract of H. tuberculatum showed the highest activity against both P. aeruginosa (13.50±0.71 mm) and S. aureus (13.00±0.00 mm) at 10 mg/ml. Furthermore 24 phenolic compounds were identified, with predominance of quinic acid, gallic acid, protocatechuic acid, syringic acid, p-coumaric acid, trans-ferulic acid, catechin (+), trans-cinnamic and silymarin. These results were further consolidated by to heatmap clustering with P. equisetiforme, H. tuberculatum, T. polium as the main antioxidant and antibacterial sources which supports their domestication and industrial use.     

Chemical Composition,Antibacterial, Antioxidant and in Vitro Antidiabetic Activities of Essential Oils from Eruca vesicaria

This work describes the study of the chemical composition and bioactivity of the essential oils (EOs) of the different organs (leaves, flowers, stems and roots) from Eruca vesicaria. According to the GC and GC/MS analysis, all the EOs were dominated by erucin (4‐methylthiobutyl isothiocyanate) with a percentage ranging from 17.9 % (leaves) to 98.5 % (roots). The isolated EOs were evaluated for their antioxidant (DPPH, ABTS and β‐carotene/linoleic acid), antibacterial and inhibitory property against α‐amylase and α‐glucosidase. Most EOs exhibited an interesting α‐glucosidase and α‐amylase inhibitory potential. The roots essential oil was found to be the most active with IC₅₀ values of 0.80±0.06 and 0.11±0.01 μg mL^?1, respectively. The essential oil of roots exhibited the highest antioxidant activity (DPPH, PI=92.76±0.01 %; ABTS, PI=78.87±0.19; and β‐carotene, PI=56.1±0.01 %). The isolated oils were also tested for their antibacterial activity against two Gram‐positive and three Gram‐negative bacteria. Moderate results have been noted by comparison with Gentamicin used as positive control.     

Four New Tirucallane Triterpenoids from the Fruits of Melia azedarach and Their Cytotoxic Activities

Four new tirucallane triterpenoids, (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxy‐25‐methoxytirucall‐7‐en‐3‐one ( 2 ), (3S,21S,23R,24S)‐21,23‐epoxy‐21,25‐dimethoxytirucall‐7‐ene‐3,24‐diol ( 8 ), (21S,23R,24R)‐21,23‐epoxy‐24‐hydroxy‐21‐methoxytirucalla‐7,25‐dien‐3‐one ( 11 ), and (21S,23R,24R)‐21,23‐epoxy‐21,24‐dihydroxytirucalla‐7,25‐dien‐3‐one ( 12 ), along with 16 known analogues, 1 , 3  –  7 , 9  –  10 , and 13  –  20 , were isolated from the fruits of Melia azedarach. Their structures were elucidated by spectroscopic methods including 1D‐ and 2D‐NMR techniques and mass spectrometry. These compounds were evaluated for their cytotoxicities against HepG2 (liver), SGC7901 (stomach), K562 (leukemia), and HL60 (leukemia) cancer cell lines. Compound 20 exhibited potent cytotoxicity against HepG2 and SGC7901 cancer cells with the IC₅₀ values of 6.9 and 6.9 μm , respectively.     

Four New Cryptoporic Acid Derivatives from the Fruiting Bodies of Cryptoporus sinensis,and Their Inhibitory Effects on Nitric Oxide Production

Four new drimane‐type sesquiterpenoid ethers of isocitric acid, named cryptoporic acids J–M, were isolated from the fruiting bodies of Cryptoporus sinensis, together with six known cryptoporic acids. Their structures were elucidated on the basis of extensive spectroscopic analyses. Among them, cryptoporic acid D showed strong inhibition against nitric oxide (NO) production in macrophages with an IC₅₀ of 45.8±3.6 μM , comparable to the positive control of hydrocortisone (IC₅₀ of 40.6±2.5 μM ).     

Chemical Constituents Isolated from Bletilla striata and Their Inhibitory Effects on Nitric Oxide Production in RAW 264.7 Cells

Bioassay‐guided fractionation of the MeOH extract of the tubers of Bletilla striata led to the isolation of two new C‐methylated flavan‐3‐ols, bletillanols A ( 1 ) and B ( 2 ), along with ten known compounds ( 3  –  12 ). Their structures were determined by using extensive spectroscopic analysis including 1D‐, 2D‐NMR, and circular dichroism data. All of the isolated compounds were tested for their inhibitory potential on the nitric oxide generation in LPS‐stimulated RAW 264.7 cells.