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

Abstract

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.

Phytochemical profile, Ethnobotanical and Biological Impacts of Various Zamia Species: A Mini-Review

“…21 Bilobetin Bilobetin has a high binding affinity to (TSDHFR) with a docking score of -8.95 kcal/mol that explain the potent expected Toxoplasmocidal activity of this compound. 12 Bilobetin was found to exhibit significant antiproliferative activities against MCF-7 in a dosedependent manner with IC50 of 57.62 μg/mL 22 . In addition, the high docking score (-7.58 kcal/mol) of bilobetin against (CDK-2).…”

“…In silico docking study indicated that vicenin-2 has a significant inhibitory effect against the toxoplasma gondii parasite due to its high affinity toward thymidylate synthase reductase dihydrofolate reductase (TSDHFR) with high docking score of -8.74 kcal/mol. 12 Vicenin-2 has a significant affinity to a cyclindependent kinase target protein (CDK-2) using a docking study with high docking score of -8.38 kcal/mol which suggest that vicenin-2 may be used as a cytotoxic drug in cancer disease. 12 Amentoflavone Amentoflavone has a high docking score of -7.63 kcal/mol against (TSDHFR) using in silico experiment which proposed that amentoflavone can afford toxoplasmocidal activity.…”

“…12 Vicenin-2 has a significant affinity to a cyclindependent kinase target protein (CDK-2) using a docking study with high docking score of -8.38 kcal/mol which suggest that vicenin-2 may be used as a cytotoxic drug in cancer disease. 12 Amentoflavone Amentoflavone has a high docking score of -7.63 kcal/mol against (TSDHFR) using in silico experiment which proposed that amentoflavone can afford toxoplasmocidal activity. 12 In addition, the high docking score (-7.60 kcal/mol) of amentoflavone against (CDK-2) suggested that amentoflavone can be a potent anticancer compound.…”

“…12 Amentoflavone Amentoflavone has a high docking score of -7.63 kcal/mol against (TSDHFR) using in silico experiment which proposed that amentoflavone can afford toxoplasmocidal activity. 12 In addition, the high docking score (-7.60 kcal/mol) of amentoflavone against (CDK-2) suggested that amentoflavone can be a potent anticancer compound.…”

“…However, a few numbers of Zamia species have been evaluated for their biological activities, it has been discovered that Zamia possesses a wide range of significant bioactivities including antioxidant, antibacterial, and cytotoxic properties [9][10][11][12] . Thus, in this review, we summarize data about the content, distribution, and bioactivity of various phytochemicals in diverse Zamia species as well as the traditional uses and biological activities of different Zamia species.…”