LC/MS-MS Analyses and in vitro anticancer activity of Tourneuxia variifolia extracts.

Several Saharan plants, despite their abundance of natural compounds, have received little attention. In this study, the chemical composition of polar extracts of Tourneuxia variifolia Coss. (Asteraceae), an endemic species to Algerian Sahara, was investigated and their anticancer activity was evaluated in vitro. The phytoconstituents of both ethyl acetate (EtOAc) and n-butanol (n-BuOH) extracts were screened using LC/MS-MS technique. The anticancer activity of the above extracts was measured against human cervical adenocarcinoma (HeLa) cell line. The LC/MS-MS analyses results revealed that twenty-seven phytochemicals in EtOAc extract and twenty-three in n-BuOH extract were identified and quantified from which isoquercetin and astragalin were the most present. Moreover; the EtOAc extract was found to have a strong anticancer activity (IC50: 46.797 ± 0.060 µg/mL). These findings identified T. variifolia as a potential plant exhibiting anticancer properties.

First determination of anticancer, cytotoxic, and in silico ADME evaluation of secondary metabolites of endemic Astragalus leucothrix Freyn & Bornm.

Isolation and characterization of anticancer activity guided secondary metabolites of endemic Astragalus leucothrix Freyn& Bornm were aimed. Aerial parts of the plant were extracted by maceration method in the solvent system methanol-chloroform (1 : 1) at room temperature. The obtained crude extract was dissolved in purified water. Then, the extract was partitioned with n-hexane, chloroform, ethyl acetate, and n-butanol, respectively. Anticancer activity tests of all the fractions were performed against HeLa and C6 cancer cells. The chloroform fraction that has highest anticancer activity was subjected to chromatographic methods such as column chromatography and thin layer chromatography. Pentyl tetratetracontanoate (1), alfalone (2), 3,6,8-tribromoquinoline (3), and 3,6,8-tribromochromenium (4) molecules were detected from this plant for the first time. The structure determinations of the isolated molecules were elucidated by methods such as 1D and 2D NMR, HPLC - TOF / MS, and GC - MS analysis. Finally, anticancer and cytotoxic activity tests of the compounds were performed. Literature review showed that 3,6,8-tribromochromenium is a new compound. IC50 values of compound 1-2 and compound 3-4 mix were determined to be 4.50 ± 0.10, 2.81 ± 0.00, 4.33 ± 0.00 µM against C6 cell, respectively. The drug likeness properties of 1-4 were obtained by SwissADME. According to Lipinski's rule of five; 2-4 could be a new potential anticancer agent.

The isolation of secondary metabolites from Rheum ribes L. and the synthesis of new semi-synthetic anthraquinones: Isolation, synthesis and biological activity.

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Iskin" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, ß-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol.

Synthesis and biological evaluation of novel urea, thiourea and squaramide diastereomers possessing sugar backbone.

A series of novel chiral 14 urea, thiourea and squaramide stereoisomers possessing carbohydrate backbones as well as amide functional groups was synthesized and characterized by their, 1H NMR, 13C NMR, FT-IR, HRMS, optical rotation, and melting points. Their antiproliferative activities were investigated against HeLa and PC3 cell lines. The compounds 9, 11 and 12 showed better activities at 25 µM against PC3 cell line with respect to the standard 5-fluorouracil (5-FU). Especially, the compounds 9 and 11 showed higher activities than the standard 5-FU even at low concentration (5 µM) against HeLa cell line. IC50 results also confirm these activities. The compounds 9, 10 and 11 have the IC50 values of 1.10 µM, 1.51 µM and 1.02 µM, respectively while 5-FU has 2.51 µM. Moreover, their cytotoxicity tests have proven that their viabilities were in between 50% and 100%.

Metabolomics of endemic six Astragalus species by combined NMR and GC-MS analysis.

INTRODUCTION: Astragalus anthylloides, A. dipsaceus, A. karamasicus, A. lycius, A. sigmoideus and A. xylobasis var. angustus are an endemic and generally grow in the Irano-Turanian phytogeographic region of Turkey. Astragalus species contain saponins, polysaccharides, and phenolics, while the toxic compounds include imidazoline alkaloids, nitro toxins, and selenium derivatives. OBJECTIVES: To apply a combined metabolomic fingerprinting approach by nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) of endemic six Astragalus species extract. METHODOLOGY: The whole plant collected in Turkey of six endemic Astragalus subsp. were dried and then extracted with hexane, chloroform, ethylacetate, n-butanol and methanol solvents, respectively. The hexane extracts were analyzed by GC-MS. Carbon-13 (13 C)-NMR analyzes of all extracts were performed. In both analyses, a biomarker was obtained. RESULTS: The hexane extracts were determined as palmitic acid, arachidic acid, behenic acid, and linolenic acid as the main components. As a result of 13 C-NMR analyzes, in hexane, chloroform, and ethylacetate the extracts detected were palmitic acid, arachidic acid, behenic acid, and linolenic acid. d-Pinitol was obtained using 13 C-NMR analyzes with n-butanol and methanol extracts. CONCLUSION: This study demonstrated that d-pinitol is a biomarker for the endemic six Astragalus subsp.

Phytochemical analysis, antiproliferative and antioxidant activities of Chrozophora tinctoria: a natural dye plant.

CONTEXT: Chrozophora tinctoria (L.) A. Juss. (Euphorbiaceae) is known as 'dyer's-croton' and used to obtain dye substances. Recently, natural antioxidants and colorants have been of interest because of their safety and therapeutic effects. OBJECTIVE: This study investigates the antiproliferative and antioxidant activities of the various extracts and fractions from C. tinctoria and analyzes their phytochemical contents. MATERIALS AND METHODS: The aerial parts of C. tinctoria were extracted with water, ethyl acetate, n-butanol, and methanol/chloroform. Phenolic compounds and other constituents of the extracts were analyzed by HPLC/TOF-MS. The ethyl acetate extract (EA) was fractionated by flash chromatography. The extracts, fractions, and major phenolic compounds were investigated for their antiproliferative activities on human cervical adenocarcinoma (HeLa) cell line at the concentrations of 5-100 µg/mL by using BrdU ELISA assay during 24 h of incubation. DPPH radical scavenging activities (5-150 µg/mL) and total phenolic contents of the samples were also evaluated. RESULTS: 4-Hydroxybenzoic acid (268.20 mg/kg), apigenin-7-glucoside (133.34 mg/kg), and gallic acid (68.92 mg/kg) were the major components of EA. CT/E-F6 (IC50 = 64.59 ± 0.01 µg/mL) exhibited the highest antiproliferative activity. CT/E-F2 (IC50= 14.0 ± 0.0 µg/mL) and some fractions displayed higher radical scavenging activity compared to synthetic antioxidant BHT (IC50 = 23.1 ± 0.0 µg/mL). Among the main phenolics, gallic acid exhibited the highest antiproliferative and radical scavenging abilities (IC50 < 5 µg/mL). CONCLUSION: In this study, we have determined the biologically active fractions and their high effects may be attributed to the presence of gallic acid.

A novel benzimidazole and other constituents with antiproliferative and antioxidant properties from Thymelaea microphylla Coss. et Dur.

A new compound (microphybenzimidazole, 7) along with the six known compounds matairesinol (1), prestegane B (2), umbelliferone (3), daphnoretin (4), microphynolide A (5) and microphynolide B (6) were isolated from Thymelaea microphylla. The structures of the pure compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1D-, 2D-NMR, and HPLC-TOF/MS. Compounds 2 and 4, as well as three fractions (F6, F6-C5, and F6-W42) obtained from a 50% (v:v) CH2Cl2:MeOH extract exhibited a selective activity against rat brain glioma cells (C6). Moreover, compound 1 and other fractions obtained from 50% (v:v) CH2Cl2:MeOH and 70% (v:v) MeOH:H2O extracts exhibited dose- and time-dependent effects on human cervical cancer cell (HeLa), as measured by xCELLigence assay. Compound 2 (IC50 = 14.0 ± 0.2 µg/mL) and fraction F5 (IC50 = 12.4 ± 0.1 µg/mL) showed higher radical scavenging ability than the synthetic agent butylated hydroxytoluene (BHT, IC50 = 22.7 ± 0.6 µg/mL).

Synthesis, characterization, and assessment of cytotoxic, antiproliferative, and antiangiogenic effects of a novel procainamide hydrochloride-poly(maleic anhydride-co-styrene) conjugate.

Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymerization reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Magnetic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations [Formula: see text] 62 µg mL(-1) (p > 0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20 µg/ml, while free PH exerted the same activity at 100 µg/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100 µg/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category.