الفهرس 
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Abstract
Gymnosperms are remarkable group of plants; they are the best example for plant evolution. They are a class of extinct plants situated between angiosperms and other lower plants. Cycadales are the oldest living members of the gymnosperms so; they have been referred as ’’living fossils’’. According to the most recent classification, cycadales have two extant families (Cycadaceae and Zamiaceae). Based on the review of literature and the availability in Egypt, two plants (C. rumphii and Z. floridana belonging to family Cycadaceae and Zamiaceae respectively had been chosen for this study due to lack of previous investigations on them in Egypt. The study has been classified into two parts: 1. Biological investigation of total methanol extract and different fractions of the two plants leaves. 2. Phytochemical investigation for the most active fraction of both plants. Part I Biological investigation of C. rumphii and Z. floridana belonging to Cycadals order cultivated in Egypt This part includes four chapters. Chapter Ⅰ: Toxoplasmocidal activity In vitro toxoplasmocidal activity of C. rumphii and Z. floridana total MeOH extracts and their different fractions were investigated using the method reported by (Kavitha et al., 2012) using cotrimoxazole as a positive control drug. The total MeOH extracts of both plants showed significant toxoplasmocidal activity against T. gondii compared to cotrimoxazole drug. The EtOAc fraction of C. rumphii showed potent toxoplasmocidal activity exceeded the positive control drug. Howerver, the n-BuOH fraction was the most active fraction against T. gondii among other Z. floridana different fractions. Chapter Ⅱ: Molecular docking study In silico molecular docking studies were conducted for compounds isolated from the most promising toxoplasmocidal fractions of both plants using MOE 2020.9010 version and Discovery Studio (DS) visualizer program. T. gondii thymidylate synthase-dihydrofolate reductase (TSDHFR) (PDB ID: 4KY4) was selected as a target for drugs that can eradicate this parasite. Using of 1UE ligand (the co-crystalized ligand inside active site) as positive control drug. The results revealed that novel 4’, 4’’’ biapigenin di-C-glucoside isolated from C. rumphii EtOAc fraction, has the highest docking score due to its huge size and the presence of three sugar moieties compared positive control ligand followed by bilobetin, 2,3 dihydrobilobetin and finally 2,3 dihydrohinokiflavone which were isolated also from C. rumphii EtOAc fraction. While the docking results of compounds isolated from n-BuOH fraction of Z. floridana indicated that bilobetin has the highest docking score followed by vicenin-2 and finally isoginkgetin due to their huge sizes in addition to the presence of two sugar moieties in vicenin-2. Chapter Ⅲ: Cytotoxic activity In vitro cytotoxic investigation for the total MeOH extract and different fractions of C. rumphii and Z. floridana in DMSO against five different carcinoma cell lines (HEPG-2, MCF-7, HCT-116, PC-3 and HELA) in addition to one normal cell line (WISH). The assay was carried out using MTT assay procedures using doxorubicin as standard drug. The results revealed that the total MeOH extract of C. rumphii was potent against three cell lines (HEPG-2 followed by HELA and finally HCT-116). However, the total MeOH extract of Z. floridana showed moderate activity against two cell lines (MCF-7 followed by HCT-116). The results of cytotoxic assay for different fractions of both plants against the most affected cell lines revealed that C. rumphii EtOAc fraction has a very strong activity against HEPG-2 followed by HELA and finally HCT-116. While, the EtOAc fraction of Z. floridana has very strong cytotoxic effect against HCT-116 and moderate cytotoxic effect against MCF-7. In addition, n-BuOH fraction of Z. floridana showed strong cytotoxic effect against the two tested cell lines MCF-7 and HCT-116. Chapter Ⅳ: Cytotoxic activity of pure compounds The EtOAc fraction of C. rumphii is the most potent fraction among all tested fractions of the two plants. So, we carried out in vitro cytotoxic investigation for seven isolated compounds from this fraction against the same cell lines to evaluate their activity. The results indicated that methyl gallate was the most potent compound followed by prunin and finally 4’,4’’’ biapigenin-8’’-C-β-D-glucopyranosyl [1’’’’’’→3’’’’’] β-D-glucopyranoside-8-C-β-D-glucopyranoside which showed strong cytotoxic effects against the tested cell lines (HEPG-2, HELA and HCT-116) compared to doxorubicin as positive control drug. Part Ⅱ Phytochemical investigation of C. rumphii and Z. floridana belonging to Cycadals order cultivated in Egypt This part includes three chapters: Chapter Ⅰ: Preliminary phytochemical screening of C. rumphii and Z. floridana leaves The findings of the phytochemical screening revealed that both plants’ leaves have sugars, sterols, triterpenes, flavonoids, tannins, and phenolics. Chapter Ⅱ: Phytochemical investigation of C. rumphii EtOAc fraction A phytochemical investigation of EtOAc fraction of C. rumphii leaves using column chromatography techniques with silica gel and Sephadex resulted in isolation of 2,3-dihydro-4′-O-methylamentoflavone, 2,3- dihydrohinokiflavone, methyl gallate, amentoflavone 4’-O-methyl ether, amentoflavone, naringenin 7-O-β-D-glucoside and a novel 4’,4’’’ biapigenin di-C-glucoside. 2,3-dihydro-4′-O-methylamentoflavone, methyl gallate and naringenin 7-O- β-D-glucoside were isolated from C. rumphii leaves for the first time. The identification of the isolated compounds were done with the help of UV, IR, ESI/MS, 1H, 13C, DEPT-Q, HSQC and HMBC NMR techniques. Chapter Ⅲ: Phytochemical investigation of Z. floridana n-BuOH fraction Column chromatography for n-BuOH fraction of Z. floridana with Diaion HP-20 followed by silica gel then, finally purification with Sephadex led to isolation of six compounds; amentoflavone 4’, 4’’’-O-methyl ether, amentoflavone 4’-O-methyl ether, syringic acid, amentoflavone, gallic acid and apigenin 6, 8-di-C-β-D-glucoside. Amentoflavone 4’, 4’’’-O-methyl ether, syringic acid, gallic acid and apigenin 6, 8-di-C-β-D-glucoside were isolated for the first time from Z. floridana. The identification of the isolated compounds were done by using UV, IR, ESI/MS, 1H, DEPT-Q, APT, HSQC and HMBC NMR techniques.