الفهرس 
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Abstract
This thesis comprises of two parts Part 1: Phytochemical studies on Launaea nudicaulis The work described in Part 1 of this thesis has been undertaken with the objective of searching for naturally occurring substances of potential biological activities in Egyptian Flora. Through this study a useful information was derived from the application of the modern techniques of chromatography column, paper, and thin layer chromatography) and spectral measurements including UV, IR, MS, 1H and 13C-NMR The introduction of this part comprises a brief account about natural products and medicinal plants, which form the backbone of traditional medicine, in the last few decades. Also the introductory part comprises detailed accounts of the previously isolated natural products from Launaea species and their structural types encountered in nature as well as some biological properties.The original part describes the chemical and biological studies on Launaea nudicaulis, and is summarized under the following titles phytochemical screening A preliminary phytochemical screening of Launaea nudicaulis was carried out for their contents of different classes of natural products. This study showed the presence of volatile substances, sterols and/or terpenes English carbohydrates and / or glycosides, flavonoids, tannins and absence of saponins and alkaloids in Launaea nudicaulis Investigation and identification of phenolic compounds from Launaea nudicaulis: Air dried whole plant of Launaea nudicaulis (750g) were crushed and extracted with chloroform / MeOH (3:1) by soaking at room temperature and the extract was evaporated under reduced pressure, then afforded dark brown gum extract (80 gm). The total extract was washed by n-hexane. The extract was subjected to silica gel column chromatography using petroleum ether (40-
60) / CHCl3 / MeOH mixtures according to increasing polarities and afforded
six major fractions. The obtained fractions were subjected to different
chromatographic techniques to afford nine compounds.
Isolation of constituentS of Launaea nudicaulis:
Nine compounds were isolated from Launaea nudicaulis, stigmasterol,
β-sitosterol, taraxasterol, lupeol, esculetin 6-O-β-D-glucopyranoside, apiginin,
apiginin7-O-β-D-glucopyranoside, luteolin-7-O-β-D-glucopyranoside and
luteolin. Structure elucidation of the isolated compounds was carried out by
chemical and spectroscopic analyses including UV, IR, MS, 1H and 13C-NMR.
Identification of unsaponifiable and saponifiable matters of Launaea
nudicaulis:
The unsaponifiable matter (USM) was subjected to gas liquid
chromatography (GLC) in order to identify its constituents. The free fatty
acids (FAs) were methylated to afford fatty acids methyl esters (FAMEs)
which were subjected to GLC in order to identify its constituents.
Identification of The constituents of unsaponifiable matter (USM):
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The constituents of UMS were identified using GLC as following:
tridecane, tetradecane, pentadecane, heptadecane, eicosan, heneicosane,
tetracosane, pentacosane, hexacosan, cholesterol and β-sitosterol.
Identification of The constituents of saponifiable matter (FAMEs):
The constituents of FAMEs were identified using GLC as following:
lauric acid, myristic acid, stearic acid, oleic acid, linolenic acid and cis-11-
eicosenoic acid.
Biological activity
Cytotoxic activity of fraction II (lupeol and taraxasterol) and total extract
of Launaea nudicaulis were tested for breast cell line.
Cytotoxic effect:
The fraction II showed moderate cytotoxic effect against MCF-7
whereas the total extract showed very weak cytotoxic effect based on its very
high IC50.
Part 2: Synthesis of some new 4-hydroxycoumarin derivatives
The work described in Part 2 of this thesis has been undertaken with the
objective of searching for different coumarin compounds with anticancer and
antimicrobial effects.
Introduction:
The introduction of this part comprised a brief account of naturally
occurring 4-hydroxycoumarin, synthesis of 4-hydroxycoumarin, some
reactions of 4-hydroxycoumarin and examples of biological activity of 4-
hydroxycoumarin.
Experimental:
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The experimental part included synthesis of 4-hydroxycoumarin-3-yl
chalcones (3a-c) and 4-hydroxycoumarin-3-ylpyridin carbonitrile derivatives
[(4a-c) and (5a-c)] as well as synthesis of 4-hydroxycoumarin-3-yl-pyrazoline
derivatives [(6a-c), (7a-c) and (8a-c)].
Results:
This part includes synthesis of nineteen compounds, fourteen of them
were new and five of them are previously synthesized, Identification of them was
carried out by spectral measurements including IR, MS and 1H NMR.
The newly synthesized compounds are 4-hydroxy-3-((E)-3-(5-
methylfuran-2-yl) acryloyl)-2H-chromen-2-one (3c), 2-amino-4-(4-
bromophenyl)-6-(4-hydroxy-2-oxo-2H-chromen-3-yl) pyridine-3-carbonitrile
(4a), 3-(5-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2Hchromen-
2-one (5a), 4-(4-chlorophenyl)-1,2-dihydro-6-(4-hydroxy-2-oxo-2Hchromen-
3-yl)-2-oxopyridine-3-carbonitrile (5b), 1,2-dihydro-6-(4-hydroxy-2-
oxo-2H-chromen-3-yl)-4-(5-methylfuran-2-yl)-2-oxopyridine-3-carbonitrile
(5c), 4-(4-bromophenyl)-1,2-dihydro-6-(4-hydroxy-2-oxo-2H-chromen-3-yl)-
2-oxopyridine-3-carbonitrile, , 3-(1-acetyl-5-(4-bromophenyl)-4,5-dihydro-
1H-pyrazol-3-yl)-4-hydroxy-2H-chromen-2-one (6a), 3-(5-(4-chlorophenyl)-
4,5-dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromen-2-one (6b), 3-(4,5-
dihydro-5-(5-methylfuran-2-yl)-1H-pyrazol-3-yl)-4-hydroxy-2H-chromen-2-
one (6c), 3-(1-acetyl-5-(4-chlorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)-4-
hydroxy-2H-chromen-2-one (7b), 3-(1-acetyl-5-(5-methylfuran-2-yl)-4,5-
dihydro-1H-pyrazol-3-yl)-4-hydroxy-2H-chromen-2-one (7c), 3-(5-(4-
bromophenyl)-4,5-dihydro-1-phenyl-1H-pyrazol-3-yl)-4-hydroxy-2Hchromen-
2-one (8a), 3-(5-(4-chlorophenyl)-4,5-dihydro-1-phenyl-1H-pyrazol-
3-yl)-4-hydroxy-2H-chromen-2-one (8b) and 3-(5-(5-methylfuran-2-yl)-4,5-
dihydro-1-phenyl-1H-pyrazol-3-yl)-4-hydroxy-2H-chromen-2-one (8c).
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Biological activity:
Some carbonitrile and pyrazole derivatives of 4-hydroxycoumarin were
synthesized and evaluated for their breast, liver cytotoxic and antimicrobial
activities.
Cytotoxic effect:
a- Compounds 4a, 5c and 6a showed moderate cytotoxic effect against
MCF-7 cell lines, while the samples 3c, 5a, 8a, and7a showed weak
cytotoxic effect. The samples 3a, 8c, 6c and 7c showed very weak
cytotoxic effect concluded from their very high IC50. Finally the sample
4c did not show any cytotoxic effect because of very high IC50.
b- For human hepatocarcinoma cell line (HepG2), samples 3c, 3a, 8c, 4c,
5a, 6a, 6c and 5c did not show any cytotoxic effect as they increased
proliferation on cell whereas the compounds 4a, 8a, 7a and 7c showed
weak cytotoxic effect.
Antimicrobial effect:
Three compounds (2, 4c and 5c) proved to be most promising against
tested bacterial organisms i.e. which were the most active against both gram
negative (Escherichia coli) and gram positive bacteria (Bacillus subtilis and
Staphelococcus aureus). It was considered as a broad spectrum antibacterial
organisms. Compounds (3a and 3b) proved to be active against bacteria and
yeast while no activity was found with fungi. Compounds (2 and 5c) proved
to be most active against candida albicans and all tested fungal organisms.
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Compounds (4b, 5a and 8b) showed moderate activity whereas the rest of the
compounds showed low effect against the tested bacterial organisms.