Toxoplasmocidal and Cytotoxic Activities Guided Isolation and Characterization of an Undescribed Bioflavonoid-di-C-glucoside from Cycas rumphii Miq. Cultivated in Egypt.

Toxoplasmosis and cancer are serious worldwide diseases, and the available drugs cause serious side effects. Investigation for new alternative therapies from natural sources is now an increasing concern. Herein, we carried out, for the first time, an in vitro screening of Cycas rumphii Miq. leaves for toxoplasmocidal effect, using Viruluent RH Toxoplasma gondii, and cytotoxic activity against HEPG-2, HCT-116 and HELA cancer cell lines using MTT assay. Among the tested extracts, the ethyl acetate fraction was the most effective against T. gondii, with an EC50 of 3.51 ± 0.2 µg/mL compared to cotrimoxazole (4.18 ± 0.01 µg/mL) and was the most potent against the tested cell lines, especially HEPG-2, with an IC50 of 6.98 ± 0.5 µg/mL compared to doxorubicin (4.50 ± 0.2 µg/mL). Seven compounds were isolated from the ethyl acetate fraction by extensive chromatographic techniques and fully elucidated using different spectroscopies. Compound (7) is an undescribed 4', 4''' biapigenin di-C-glucoside, which showed a strong cytotoxic activity. Four known biflavonoids (1, 2, 4 and 5) in addition to a phenolic acid ester (3) and a flavonoid glycoside (6) were also isolated. Compounds (1, 3 and 6) were reported for the first time from C. rumphii.

In Vitro Characterization of Inhibitors for Lung A549 and Leukemia K562 Cell Lines from Fungal Transformation of Arecoline Supported by In Silico Docking to M3-mAChR and ADME Prediction.

The search for anticancer drugs is of continuous interest. Arecoline is an alkaloid with anticancer activity. Herein, the metabolism of arecoline through fungal transformation was investigated for the discovery of potential anticancer drugs with higher activity and selectivity. Compounds 1-5 were isolated, and their structures were fully elucidated using various spectroscopic analyses, including 1D and 2D NMR, ESIMS, and HRESIMS. This is the first report for the isolation of compounds 1 and 2. An MTT assay was performed to determine the cytotoxic activity of arecoline and its metabolites in vitro using non-small-cell lung cancer A549 and leukemia K562 cell lines compared to staurosporine and doxorubicin as positive controls. For the non-small-cell lung A549 cell line, arecoline hydrobromide, staurosporine, and doxorubicin resulted in IC50 values of 11.73 ± 0.71 µM, 10.47 ± 0.64 µM, and 5.05 ± 0.13 µM, respectively, while compounds 1, 3, and 5 exhibited IC50 values of 3.08 ± 0.19 µM, 7.33 ± 0.45 µM, and 3.29 ± 0.20 µM, respectively. For the leukemia K562 cell line, the IC50 values of arecoline hydrobromide, staurosporine, and doxorubicin were 15.3 ± 1.08 µM, 5.07 ± 0.36 µM, and 6.94 ± 0.21 µM, respectively, while the IC50 values of compounds 1, 3 and 5 were 1.56 ± 0.11 µM, 3.33 ± 0.24 µM, and 2.15 ± 0.15 µM, respectively. The selectivity index value of these compounds was higher than 3. These results indicated that compounds 1, 3, and 5 are very strong cytotoxic agents with higher activity than the positive controls and good selectivity toward the tested cancer cell lines. Cell cycle arrest was then studied by flow cytometry to investigate the apoptotic mechanism. Docking simulation revealed that most compounds possessed good binding poses and favorable protein-ligand interactions with muscarinic acetylcholine receptor M3-mAChR protein. In silico study of pharmacokinetics using SwissADME predicted compounds 1-5 to be drug-like with a high probability of good oral bioavailability.

Triterpenoids from the aerial parts of Anabasis articulata (Forssk) Moq: gastroprotective effect in vivo with in silico studies, cytotoxic and antimicrobial activities.

A new triterpenoid named 3ß,20α-dihydroxy-30-nor-olean-12-ene-23,28 dioic acid (4) along with 3ß-hydroxy-23-aldehyde-lup-20(29)-ene-28-oic acid (1), 3ß-hydroxy-23-aldehyde-30-nor-olean-12,20(29)-diene-28-oic acid (2), 3ß-hydroxy-lup-20(29)-ene-23,28 dioic acid (3), 3ß-hydroxy-lup-20(29)-ene-23,28 dioic acid-23-O-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucuronopyranosyl-lup-20(29)-ene-23,28 dioic acid-28-O-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucuronopyranosyl-lup-20(29)-ene-23-aldehyde-28-oic acid-28-O-ß-D glucopyranosyl ester (7) were isolated for the first time from the aerial parts of Anabasis articulata (Forssk) Moq. Isolated pure compounds were structurally elucidated using spectral analysis. Cytotoxic, antimicrobial, antiulcer activities and antioxidant parameters were evaluated using the total methanol extract and its successive fractions. The methylene chloride fraction showed strong cytotoxic activity against HepG-2 (6.9 µg/ml) and HCT-116 (5.5 µg/ml) tumour cell lines in comparative with 5-fluorouracil (7.9 µg/ml). Treatment of indomethacin induced ulcerated rats with ethyl acetate fraction (400 mg/kg, p.o./day) achieved reduced Ulcer index (0.18), potent inhibition percentage of ulceration (84.86%) in comparison to ranitidine and high antioxidant effect. Compound(6) exhibited high docking score against gastric H+/K+ ATPase.

Evaluation of Zamia floridana A. DC. Leaves and Its Isolated Secondary Metabolites as Natural Anti-Toxoplasma and Anti-Cancer Agents Using In Vitro and In Silico Studies.

Toxoplasmosis and cancer are life-threatening diseases with worldwide distribution. However, currently used chemosynthetic treatments are not devoid of their own intrinsic problems. Natural metabolites are gaining attention due to their lower side effects. In this study, we investigated for the first time Zamia floridana leaves extract and its different fractions for their toxoplasmocidal activity, using Virulent RH Toxoplasma gondii, and cytotoxic activity against MCF-7 and HCT-116 cancer cell lines using MTT assay. The n-butanol fraction was the most potent fraction against T. gondii with an EC50 of 7.16 ± 0.4 µg/mL compared to cotrimoxazole (4.18 ± 0.3 µg/mL). In addition, the n-BuOH fraction showed a significant cytotoxicity against MCF-7 and HCT-116 with IC50 of 12.33 ± 1.1 and 17.88 ± 1.4 µg/mL, respectively, compared to doxorubicin (4.17 ± 0.2 and 5.23 ± 0.3 µg/mL, respectively), with higher safety index against normal cell line (WISH). Therefore, the n-BuOH fraction was investigated for its phytochemicals using extensive chromatographic techniques, which led to the isolation of six compounds that were fully characterized using different spectroscopic techniques. Three biflavonoids (1, 2 and 4) in addition to two phenolic acid derivatives (3 and 5) and a flavonoid glycoside (6) were isolated. Compounds (1, 3, 5 and 6) were reported for the first time from Z. floridana. In silico docking studies for toxoplasmocidal and cytotoxic effects of these compounds revealed that compounds (1, 2, 4 and 6) have promising inhibition potential of either thymidylate synthase-dihydrofolate reductase (TS-DHFR) or cyclin dependent kinase 2 (CDK2) target proteins. This study is considered the first report of chemical and biological investigation of Z. floridana leaves.

Hepatoprotective, cytotoxic, antimicrobial and antioxidant activities of Dioon spinulosum leaves Dyer Ex Eichler and its isolated secondary metabolites.

Given the lack of adequate research on Dioon spinulosum (D. spinulosum) Dyer Ex Eichler, this study was conducted focusing on different biological activities and phytochemical investigation of D. spinulosum for the first time. D. spinulosum showed strong protective activity against DNA damage and potent activity against VERO cell line. It also presented antimicrobial and hepatoprotective activity. Phytochemical investigation of the leaves resulted in isolation of two new flavonoids, apigenin 7-O-α-d-glucopyranoside (15) and amentoflavone 7-O-α-l-rhamnopyranoside (16), in addition to fifteen known compounds: phytone (1), trans-phytol (2), ß-sitosterol (3), stigmasterol (4), oliveriflavone (5), 7,4',7″,4″'-tetramethylamentoflavone (6), 7,4',7''-trimethylamentoflavone (7), scaidopitysin (8), bilobetin (9), isoginkgetin (10), aromadendrin (11), sotusflavone (12), engeletin (14) and eriocitrin (17) for the first time together with amentoflavone (13). Compounds (11) and (13) displayed very strong cytotoxic activity and showed the highest protective activity against DNA damage.