Mansour Znati

Antioxidant, 5-Lipoxygenase Inhibitory and Cytotoxic Activities of Compounds Isolated from the Ferula lutea Flowers

A phytochemical investigation of the Ferula lutea (Poir.) Maire flowers has led to the isolation of a new compound, (E)-5-ethylidenefuran-2(5H)-one-5-O-β-d-glucopyranoside (1), designated ferunide, 4-hydroxy-3-methylbut-2-enoic acid (2), reported for the first time as a natural product, together with nine known compounds, verbenone-5-O-β-d-glucopyranoside (3), 5-O-caffeoylquinic acid (4), methyl caffeate (5), methyl 3,5-O-dicaffeoylquinate (6), 3,5-O-dicaffeoylquinic acid (7), isorhamnetin-3-O-α-l-rhamnopyranosyl(1→6)-β-d-glucopyranoside, narcissin (8), (−)-marmesin (9), isoimperatorin (10) and 2,3,6-trimethylbenzaldehyde (11). Compounds 3–10 were identified for the first time in Ferula genus. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments, mass spectroscopy and X-ray diffraction analysis (compound 2), as well as by comparison with literature data. The antioxidant, anti-inflammatory and cytotoxic activities of isolated compounds were evaluated. Results showed that compound 7 exhibited the highest antioxidant activity with IC50 values of 18 ± 0.5 µmol/L and 19.7 ± 0.7 µmol/L by DPPH radical and ABTS radical cation, respectively. The compound 6 exhibited the highest anti-inflammatory activity with an IC50 value of 5.3 ± 0.1 µmol/L against 5-lipoxygenase. In addition, compound 5 was found to be the most cytotoxic, with IC50 values of 22.5 ± 2.4 µmol/L, 17.8 ± 1.1 µmol/L and 25 ± 1.1 µmol/L against the HCT-116, IGROV-1 and OVCAR-3 cell lines, respectively.

Synthesis of new isoxazoline derivatives from harmine and evaluation of their anti-Alzheimer, anti-cancer and anti-inflammatory activities

Abstract In our study, a series of new harmine derivatives has been prepared by cycloaddition reaction using various arylnitrile oxides and evaluated in vitro against acetylcholinesterase and 5-lipoxygenase enzymes, MCF7 and HCT116 cancer cell lines. Some of these molecules have been shown to be potent inhibitors of acetylcholinesterase and MCF7 cell line. The greatest activity against acetylcholinesterase (IC50 = 10.4 µM) was obtained for harmine 1 and cytotoxic activities (IC50 = 0.2 µM) for compound 3a. Two derivatives 3e and 3f with the thiophene and furan systems, respectively, showed good activity against 5- lipoxygenase enzyme (IC50 = 29.2 and 55.5 µM, respectively).

Chemical Composition, Biological and Cytotoxic Activities of Plant Extracts and Compounds Isolated from Ferula lutea

The present work describes the phytochemical study on Ferula lutea flowers. Total phenolics and flavonoids of the n-butanol and ethyl acetate extracts were quantified (phenolics [40.68–52.29 mg gallic acid equivalent/g of dry weight], flavonoids [12.38–14.72 mg quercitin/g dry weight]). Two diastereoisomers were isolated and identified using spectroscopic techniques (1D, 2D NMR and GC-MS). The extracts and diastereoisomers were tested for antioxidant, antiacetylcholinesterase, antimicrobial, antidiabectic, cytotoxic (leukemia cell line) activities and allelopathic potentialities. The strongest antioxidant activity was obtained for the ethyl acetate extract (IC50 = 12.8 ± 1.29 µg/mL). The two extracts exhibited high antidiabetic activity (54.1 and 52.1% at 40 µg/mL).

Synthesis of New Harmine Isoxazoles and Evaluation of their Potential Anti-Alzheimer, Anti-inflammatory, and Anticancer Activities

Harmine 1 was extracted from the seeds of Peganum harmala. From this natural molecule, a new series of isoxazole derivatives with complete regiospecificity were prepared using 1,3-dipolar cycloaddition reactions with various arylnitrile oxides. Harmine and its derivatives were characterized by (1)H NMR, (13)C NMR and HRMS. The evaluation of their anti-acetylcholinesterase (AChE), anti-5-lipoxygenase (5-LOX), anti-xanthine oxidase (XOD) and anticancer activities were studied in vitro against AChE, 5-LOX and XOD enzymes, respectively, and in HTC-116, MCF7 and OVCAR-3 cancer cell lines. The prepared derivatives were shown to be inactive against the XOD enzyme (0-38.3 ± 1.9% at 100 µM). Compound 2 exhibited the best anti-AChE activity (IC50=1.9 ± 1.5 µM). Derivatives 3a, 3b and 3d had moderate cytotoxic activities (IC50=5.0 ± 0.3 µM (3a) and IC50=6.3 ± 0.4 µM (3b) against HCT 116 cells, IC50=5.0 ± 1.0 µM (3d) against MCF7 cells).

Chemical Composition and in vitro Evaluation of Antimicrobial, Antioxidant and Antigerminative Properties of the Seed Oil from the Tunisian Endemic Ferula tunetana Pomel ex Batt

Essential oil of the seeds from the endemic Tunisian plant Ferula tunetana Pomel ex Batt. was analyzed for its chemical composition and screened for its antimicrobial, antioxidant and antigerminative properties. The chemical composition of the isolated oil is reported for the first time. According to the GC/FID, GC/MS and 13C‐NMR analysis results; 18 compounds were identified accounting for 84.6% of the total oil. The chemical composition of this essential oil was characterized by the presence of a high proportion of monoterpene hydrocarbons (77.3%) followed by oxygenated sesquiterpenes (4.1%) and sesquiterpene hydrocarbons (3.2%). α‐Pinene (39.8%), β‐pinene (11.5%) and (Z)‐β‐ocimene (7.5%) were the predominant compounds. Moreover, the isolated oil was tested for its antimicrobial activity using the disc‐diffusion and the microdilution assays against six Gram‐positive and five Gram‐negative bacteria as well as towards two Candida species. The isolated oil was tested also for its antioxidant activity against DPPH, ABTS, O2∙ and hydrogen peroxide (H2O2), and for its antigerminative potential. It was found that it exhibited interesting antimicrobial activity against Salmonella typhimurium LT2 DT104 (inhibition zone (IZ) 16.2 ± 1.0 mm) and Bacillus cereus ATCC 14579 (IZ 15.8 ± 1.0 mm). However, it exerted a moderate antioxidant activity against H2O2 (IC50 78.2 ± 2.98 μg/ml) and towards O2∙ (IC50 89.2 ± 3.82 μg/ml). The antigerminative effect of this oil was also evaluated in this work. Results showed a toxic effect.

Chemical composition, antibacterial and cytotoxic activities of the essential oil from the flowers of Tunisian Convolvulus althaeoides L.

This study describes the chemical composition and evaluates the antibacterial and the cytotoxic effects of the essential oil from the flowers of Convolvulus althaeoides. Its chemical composition, determined by GC and GC–MS, is reported for the first time. A total of 24 compounds, accounting for 95.5% of the total oil, have been identified. The oil was characterised by a high proportion of sesquiterpene hydrocarbons (36.3%), followed by oxygenated sesquiterpenes (34.7%) and oxygenated monoterpenes (24.5%). The main compounds were germacrene D (12.5%), T-cadinol (11.8%) and verbenone (6.9%). The essential oil was tested for its antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis and the clinical strain Acinetobacter sp. as well as facts cytotoxic activity towards the human breast cancer cells MCF-7. This oil did not exhibit significant antibacterial activity against the tested bacteria; however, it exerted a significant cytotoxic activity against the tested cell line (IC50 = 8.16 μg/mL).

Phytochemical and biological studies of Atriplex inflata f. Muell.: isolation of secondary bioactive metabolites

This work describes the phytochemical and biological investigation of the Tunisian Atriplex inflata F. Muell (Chenopodiaceae).

Chemical Composition, Antimicrobial, Anti-acetylcholinesterase and Cytotoxic Activities of the Root Essential oil from the Tunisian Ferula lutea (Poir.) Maire (Apiaceae)

Abstract The essential oil of the roots of Ferula lutea from Tunisia, obtained by hydrodistillation was analyzed by combination of GC(FID), GC-MS and 13C-NMR spectroscopy. The chemical composition of root oil of this species is reported for the first time. This essential oil was characterized by a high proportion of monoterpene hydrocarbons. δ-3-Carene (72.6%) was, by far, the major component of the essential oil followed by α-pinene (5.8%), myrcene (5.1%) and α-phellandrene (4.0%). Furthermore, the isolated oil was tested for its antimicrobial activity using the disc-diffusion and the microdilution essays against six Gram-positive and five Gram-negative bacteria as well as towards eight Candida species. It was found that this oil, exhibited interesting antibacterial and anticandidal activity (MIC = 39 mg/mL against Escherichia coli ATCC 25922, MIC = 78 mg/mL against Salmonella typhimurium ATCC 13311 and MIC = 156 mg/mL against Candida albicans. The anti-acetylcholinesterase and cytotoxic effects of this oil were also evaluated in this work. Results showed that this oil exhibits a high anti-acetylcholinesterase activity (IC50 = 28.56±1.87 μg/mL) and cytotoxic activity (IC50 = 26.39±3.98 μg/mL) towards the cell line HT-29.

Design and semisynthesis of new herbicide as 1,2,3-triazole derivatives of the natural maslinic acid

Graphical abstract Figure. No Caption available. HighlightsNew hybrid compounds based on maslinic acid (MA) from Olea europaea were synthesized.The semisynthesis was achieved through CuAAC under microwave conditions.Development of new inhibitors (up to 100%) of Lactuca sativa growth. ABSTRACT Interesting biological activities (anti‐inflammatory, anticancer, antiviral, antioxidant, antidiabetic…) have been reported for maslinic acid (MA) and MA‐based compounds. In continuation of our previous work on MA, herbicide potential of Tunisian plant extracts and 1,4‐triazolyl derivatives of MA, we now wish to report semisynthesis of new MA‐based triazole hybrid compounds with herbicide potential. These compounds were synthesized through Cu‐catalyzed azide‐alkyne cycloaddition (CuAAC) under microwave irradiation conditions between propargylated MA and a series of phthalimide azides. Here, the first partner of CuAAC reaction (propargylated MA) resulted from propargylation of C‐28 carboxylic acid group of isolated MA from the well‐known Mediterranean plant Olea europaea L. (Oleaceae). So far, phthalimide azide derivatives were achieved by trapping of N‐acyliminium ion, in‐situ generated under catalytic condition of Bi(OTf)3, by aromatic nucleophiles. The cycloaddition reaction afforded regiospecifically 1,4‐disubstituted triazoles in good yields. The latter hybrid compounds were shown to exhibit a high inhibition potential of seed germination. This constitutes the first step in development of potent herbicides since one of the final semisynthesized structures can serve as a promising lead candidate for further studies.

Synthesis of new anticancer and anti-inflammatory isoxazolines and aziridines from the natural (-)-deltoin

This work describes the synthesis, the bioactivity and the structure–activity relationship of new derivatives from a natural coumarin.