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

Abstract

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.

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

“…The IR spectrum of compound ( 4 ) was found identical to an authentic sample of amentoflavone ( Figure S15B ). The spectral data of compound ( 4 ) was identical to those reported in the literature for amentoflavone [ 2 , 24 , 32 ].…”

“…The IR spectrum of compound ( 2 ) was found identical to an authentic sample of bilobetin ( Figure S8B ). By comparing our data to those reported in the literature [ 2 , 24 , 27 , 28 ], compound ( 2 ) was identified as amentoflavone 4′- O -methyl ether (bilobetin).…”

“…Four compounds of them were isolated for the first time from Z. floridana leaves. These compounds were tested previously in other studies against breast and colon cell lines in vitro and they showed cytotoxic effects [ 2 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ], which could account for the cytotoxic effect of the n -butanol fraction of Z. floridana. The potent toxoplasmocidal effect of n -BuOH fraction encouraged us to investigate and predict the possible mechanisms of these compounds to inhibit T. gondii using in silico molecular docking study.…”

“…It is commonly referred to as the cycads. Cycadaceae and Zamiaceae are the most important families in this order due to their large number of species and wide range of biological activities such as Cycas revoluta , that has cytotoxic and antioxidant activities and Cycas rumphii , which was previously reported as a natural source for toxoplasmocidal and cytotoxic agents [ 2 , 3 ]. In addition, various biological effects have been reported for different species of Zamiaceae such as the antimicrobial effect of Dioon spinulosum and the antileishmanial activity of Zamai lindenii [ 4 , 5 ].…”

Cycadaceae: An Important Source for Biflavonoids and Various Pharmacological Effects of Different Cycas Species

“…Additionally, in our previous study of the cytotoxic capability of C. rumphii in different extracts, we found that strong cytotoxic activity is detected in the whole methanol extract of C. rumphii against HePG-2, HeLA, and HCT-116, with IC50 values of 10.09, 11.79, and 12.58 µg/mL, respectively compared to doxorubicin as a standard drug. Interestingly, doxorubicin, the positive control, had an IC50 of 7.79 µg/mL while the entire MeOH extract of C. rumphii had an IC50 of 53.72 µg/mL against the normal cell line (WISH) 10 . As a result, it is believed that C. rumphii MeOH extracts are less harmful to healthy cells and more effective against cancer cells.…”