Ayse Sahin Yaglioglu

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 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.

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

Abstract 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.

Antiproliferative activities of several plant extracts from Turkey on rat brain tumor and human cervix carcinoma cell lines

Turkey has a wide range of flora and fauna due to its climatic diversity. Medicinal plants from Turkey have been used since ancient times for their primary health care. In this study, we examined antiproliferative activities of the extracts from Crataegus monogyna, Vitis vinifera, Glycrrhiza glabra, Alnus glutinosa L. gaertn, and Alcea rosea against rat brain tumor (C6) and human cervical cancer (HeLa) cell lines. The results were compared with the standard anticancer drugs 5-Flurouracil (5-FU) and Cisplatin. C. monogyna, V. vinifera and A. rosea exhibited better antiproliferative activity than 5-FU and cisplatin at 100-75 µg/mL concentrations, against C6 cell lines. On the other hand, C. monogyna and V. vinifera extracts showed considerable antiproliferative activity against HeLa cells compared with 5-FU and cisplatin at 100-75 µg/mL. It can be suggested that, C. monogyna, A. glutinosa L. gaertn, V. vinifera and A. rosea extracts could be developed as an anticancer drug. GRAPHICAL ABSTRACT

Bioactivity-Guided Isolation of Antiproliferative Sesquiterpene Lactones from Centaurea solstitialis L. ssp. solstitialis

Centaurea solstitialis L. ssp. solstitialis (CSS) has been used as medicine for various diseases. In this work, root, stem and flower parts of the plant were separately extracted with methanol to execute bioassay-guided isolation. Antiproliferative activities of each extracts on C6 cells (Rat Brain tumor cells) and HeLa cells (human uterus carcinoma) were investigated in vitro. The methanol extract of stem exhibited the most antiproliferative activity therefore isolation of active compounds was carried out for stem of the plant. Methanol extract of stem was boiled at 97 °C for 2 hours in water and then hexane and ethyl acetate were extracted sequentially. Solstitialin A 1 and 15-dechloro-15-hydroxychlorojanerin 2 were isolated from ethyl acetate extract by column chromatography and identified by spectroscopic techniques. Solstitialin A 1 was isolated from CSS and 15-dechloro-15-hydroxychlorojanerin 2 was isolated from Saussurea lipschitz and Rhaponticum pulchrum previously. These two compounds exhibited very high antiproliferative activity on C6 and HeLa cells. IC50 and IC75 values of compound 1 were obtained as 10.78 and 53.65 against C6 cell and as 48.78 and 68.52 against HeLa, respectively. IC50 and IC75 values of compound 2 were determined as 432.43 and 109.79 against C6 cell.

Comparative Essential Oil Composition of Flowers, Leaves, and Stems of Centaurea polypodiifolia var. polypodiifolia

The genus Centaurea belonging to the family Asteracea (Compositae) is represented by more than 170 species [1], 109 of which are endemic in the flora of Turkey [2,3]. Many members of this genus, C. cyanus L. C. behen, calcitrapa L., C. drabifolia Sm. C. chilensis, etc., are used as medicinal herb in remedial treatments [4] because of their biological activity such as antifungal [5], anti-inflammatory [6], antimicrobial [7], hypoglycemic, cytotoxic, and phytotoxic [8]. Studies on the essential oil composition of Centaurea species are incomplete and deal with only a few species. Some recent studies focus on the essential oil composition of some Centaurea species such as C. spruneri, C. raphanina subsp. mixta [9], C. thessala subsp. drakiensis, C. pelia, C. zuccariniana [10], C. pseudoscabiosa subsp. pseudoscabiosa, C. hadimensis [11], C. cineraria L. subsp. umbrosa (Lacaita) Pign., C. napifolia L. [12], C. kotschyi var. kotschyi, C. kotschyi var. decumbens [13], C. sessilis, and C. armena [14]. According to the literature, there is no record on the essential oil of C. polypodiifolia. In the present work, the essential oil composition of C. polypodiifolia var. polypodiifolia was investigated and the variation of the oil in the flowers, leaves, and stems was compared. Essential oils obtained from different parts of C. polypodiifolia var. polypodiifolia were similar in yield (ca. 0.01% based on dried material). The components of the oil are summarized in Table 1, with their percentages and relative retention indices. In total, 55 components were identified, representing 91.2, 76.4, and 95.0% of total essential oil in flowers, stems, and leaves, respectively. The volatile fractions were a mixture of different substances including three alkanes and alkenes, three alcohols, five aldehydes, two monoterpene hydrocarbons, 11 oxygenated monoterpenes, 13 sesquiterpene hydrocarbons, 14 oxygenated sesquiterpenes, two diterpenoids, and two fatty acids. While oxygenated sesquiterpenes are presented in greater amounts in oil obtained from flowers and stem at 29.9 and 43.3%, respectively, sesquiterpene hydrocarbons are the major fractions in the oil isolated from leaves with 43.5%. The main component was caryophyllene oxide (17.6%), an oxygenated sesquiterpenes, from the oil of flowers, followed by abundant components such as cis,cis,cis-7,10,13-hexadecatrienal (15.0%), an aldehyds, tetracosane (14.9%), heneicosane (12.9%), and alkanes. The oxygenated sesquiterpene bisabolol (23.9%) was the main component in the stem oil compared to that in flowers. trans-Nerolidol (8.5%) and caryophyllene oxide (8.1%) are the other major components. The fatty acid n-hexadecanoic acid of stem oil (10.8%) is markedly higher than that of flower (2.2%) and leaf oil (3.4%). COMPARATIVE ESSENTIAL OIL COMPOSITION OF FLOWERS, LEAVES, AND STEMS OF Centaurea polypodiifolia var. polypodiifolia

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

Abstract 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)

Chemical constituents and antiproliferative effects of cultured Mougeotia nummuloides and Spirulina major against cancerous cell lines.

Abstract In this study, the effect of Mougeotia nummuloides and Spirulina major on Vero cells (African green monkey kidney), C6 cells (rat brain tumor cells) and HeLa cells (human uterus carcinoma) was investigated in vitro. The antiproliferative effect of the methanol extract of M. nummuloides and S. major compared with 5-fluorourasil (5-FU) and cisplatin was tested at various concentrations using the BrdU Cell Proliferation ELISA. Both M. nummuloides and S. major extracts significantly inhibited the proliferation of Vero, HeLa and C6 cancer cell lines with IC50 and IC75 values. The M. nummuloides extract exhibited higher activity than 5-FU and cisplatin on Vero and C6 cells at high concentrations. The S. major extract revealed better antifproliferative activity than standards against Vero cells at 500 μg/mL. The compounds of methanol extracts were determined by GC-MS after the silylation process. Trehalose, monostearin and 1-monopalmitin were detected as major products in the M. nummuloides extract where as in the S. major extract; monostearin, 1-monopalmitin and hexyl alcohol were the main constituents.

Phytochemical Screening, Antiproliferative and Antioxidant Properties of Various Extracts from Endemic Origanum acutidens

AIM AND OBJECTIVE Origanum acutidens (Hand.-Mazz.) Ietsw. is an endemic and perennial plant grown mainly in East Anatolia. Recently, natural plant products have attracted interest due to their safety and therapeutic effects. Therefore, the aim of this study was to investigate phytochemical contents and biological effects of Origanum acutidens. MATERIALS AND METHODS The aerial parts of O. acutidens were extracted with water, ethyl acetate, nbutanol, and methanol/chloroform solvents. 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 and fractions were investigated for their antiproliferative activities on human cervical adenocarcinoma (HeLa) cell line by using BrdU ELISA assay. Antioxidant activities of the extracts and fractions were evaluated by complementary test systems, namely determination of total phenolic contents, metal chelating ability and DPPH radical scavenging assay. RESULTS Among the extracts, Ethyl Acetate extract (EA) exhibited the highest antiproliferative activity (IC50 = 15.71 ± 0.04 µg/mL) on HeLa cells. It was therefore fractionated by flash chromatography to obtain 10 fractions which were investigated for their phenolic compounds and bioactivities. Rosmarinic acid was determined as the major component of EA and its fractions. EA exhibited higher antiproliferative activity against HeLa cell line than its fractions and 5-fluorouracil (5-FU) at the concentration of 100 µg/mL. EA and its fractions (F10, F6, F4, F7, F3, and F2) displayed higher radical scavenging activity compared to Butylated Hydroxytoluene (BHT). These effects may be attributed to the presence of rosmarinic acid in EA and its active fractions. CONCLUSION This study demonstrated that O. acutidens is an essential natural source of polyphenols and a potent natural antioxidant and antiproliferative agent for food and pharmaceutical industries.