الفهرس 
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Abstract
Isolation and structure elucidation of natural products from Thevetia peruviana The use of natural products extracted from plants for medical purposes can be traced to the beginnings of civilization. In fact, early work on cultivation and classification of plants has much to do with their use in the treatment of many different types of human ailments and up until the identification of active principles and their synthesis on an industrial scale at the end of the nineteenth century, natural products were the principal source of medicines. Since then, their share of the pharmaceutical market declined significantly and nowadays their relative importance has oscillated according to the discoveries coming out of research laboratories and the strategies of large pharmaceutical companies. Thevetia peruviana K. Schum (= T. neriifolia, Juss) occupied a significant place among the many genera of Apocynaceae rich in cardiac glycosides, especially its seeds. All parts of the T. peruviana are notable for its toxicity as a result of containing cardiac glycosides (toxins) also as antifungal, antimicrobial, anticancer and anti-oxidative properties. Furthermore, these compounds showed cytotoxic, antineoplastic, anti-mycobacterial, antidiarrheal, immunomodulatory and anti-inflammatory activities and exert cardio tonic and insect antifeedant or repellent activities. In addition, the plant inhibits HIV-1 integrase and HIV-1 reverse transcriptase. The present study is embodied in two parts. Part I, described the isolation, characterization and structure elucidation of forty four compounds from T. peruviana, which can be classified into eight sterols [six cardiac glycosides (2-7), two pregnans (25, 26)], nineteen acetogenins (fats derivatives) (8, 10-12, 15-21, 23, 24, 27, 28, 31, 42, 45), one flavonoids (1), eleven terpenes (9, 13, 14, 22, 30, 32-35, 36, 39, 40) and four shikimates (37, 41, 43, 44). Extensive diverse chromatographic (CC and PTLC) and spectrophotometric (1H-NMR, 13C-NMR, GC/MS, ESI-MS, H-HCOSY, HSQC and HMBC) techniques were employed to elucidate the structures of the compounds noted in part I. This is the first report of acacetin (apigenin 4’-methyl ether) (1) from this species as well as the first identification and isolation of cannogenin 3-O-β-D-6``-methyl ether glucosyl-(1→4)-α-L-thevetoside (2). The structural formulas of the identified compounds: I- Sterols i) Cardiac glycosides ii) Pregnans II- Acetogenins (fats derivatives) III- Flavonoids IV- Terpenes V- Shikimates Part II of the thesis deals with the potential antioxidants and cytotoxicity activities of T. peruviana fractions and pure isolates. The in vitro antioxidant potential of T. peruviana was evaluated with DPPH, ABTS and SOD-like activity assays. Butanol leaves, butanol seeds, ethyl acetate leaves, ethyl acetate seeds, and methylene chloride leaves extracts exhibited the most significant free radicals scavenging activity when compared to the standard antioxidant ascorbic acid in DPPH and ABTS assays as shown in Figure 55. An inspection of the data indicates that the ethyl acetate seeds and methylene chloride leaves extracts exhibited the potent anti-oxidative activity using superoxide dismutase like activity assay when compared to the standard antioxidant ascorbic acid, as shown in Figure 56. The cytotoxicity of T. peruviana fractions and pure isolates were assessed against the normal cell line WI38, and cancer cell lines namely; colon cancer cell lines HCT116, hepatocellular carcinoma cell line HepG2 and breast cancer cell line MCF7. After 48 h incubation period of the extracts with normal cell line WI38, it is found that Compound (5), Butanol seeds, Compound (1), Compound (3), and Compound (4) are the safest compounds with the least cytotoxicity against normal cells. While Ethyl acetate Seeds, Methylene chloride leaves, and Compound (6) and (7) showed the highest cytotoxicity against all cancer cell lines (HCT116, HepG2, and MCF7). Compound (6) and (7) exhibited a significant selectivity against HCT116, while methylene chloride leaves and Ethyl acetate Seeds showed high selectivity towards HepG2 and MCF7 with IC50 less than 10 µM as shown in Figure 57. The viability of cancer cell lines was significantly.