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العنوان
Biochemical Study of Novel Phthalimide Analogs
on Experimentally Induced Liver Fibrosis in Mice/
المؤلف
Abo Alela,Alshimaa Attia Amin.
هيئة الاعداد
باحث / الشيماء عطيه امين ابو العلا
مشرف / مجدي عبد الحميد زهران
مشرف / ايهاب مصطفى طوسون
مناقش / فاتن زهران محمد
مناقش / بيشوي يوسف الاعرج
الموضوع
phthalimide analogs fibrosis Chemistry.
تاريخ النشر
2022
عدد الصفحات
101 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
Organic Chemistry
تاريخ الإجازة
1/8/2022
مكان الإجازة
جامعة المنوفية - كلية العلوم - الكيمياء
الفهرس
Only 14 pages are availabe for public view

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Abstract

Phthalimide is an important pharmacophore and has a privileged
structure in drug discovery . It has been reported that the phthalimide
moiety is a very important biologically active pharmacophore.
Antimicrobial properties of phthalimide derivatives were reported.
A series of novel phthalimide analogs containing brominated indole
moiety were synthesized compounds showed broad spectrum activity to
words different fungi and potent anticancer activity on different cancer
cell line. They showed ability to bind topoisomerase || DNA gyrase.
Moreover, they augment caspase -3 levels and declined Bcl-2 expression.
Liver fibrosis is a frequent event which follows a repeated or chronic
insult of sufficient intensity to tigger a “wound healing “reaction.
Characterized by excessive connective tissue deposition in extra
Plan of the work:
The experiments will be carried out on adult albino mice. Animals will
be maintained at 25 °C± 2°C under standard conditions in the animal
house. Animal care, maintenance and experiments were performed under
the supervision of the Institutional Animal Ethics Committee.
Animals will be divided into four groups:
• group I: (normal control); mice without any treatment.
• group II: (CCl4 model group); mice injected withCCl4 (0.4
mL/kg) mixed in olive oil at ratio (1:4) twice a week for 6
consecutive weeks.
• group III: mice injected with CCl4 and i.p. treated with the
phthalimide.
• group IV: mice injected with CCl4 and i.p. treated with
Thalidomide (reference drug).
At the end of experiment, animal’s euthanasia will be done; liver
tissues will be collected for estimation of the mentioned
parameters:
(1) Histopathology examination of liver.
(2) Determination of Bcl-2, Caspase-3, VEGF and PECNA, and by
immunohistochemistry.
(3) Measurement of Malondialdehyde (MDA), Super oxide
(4) dismutase (SOD), Catalase (CAT), and Glutathione per oxidase
(GPx) concentration in liver tissues homogenates.
(5) Determination of TNF-? level in liver tissues
(6) 5-Determination of NF-?B-p65 protein level in liver tissues
Histopathological examination of liver tissue
1- Normal mice: Normal hepatocytes arranged in cords around the
central vein were presented in liver tissues.
2- the liver tissues of LI model group showed multiple
histopathological changes demonstrated by centrilobular hepatic
necrosis, fibroblastic cells proliferation
3- The treatment with phthalimide analog, (30 mg/kg body weight),
improved these pathologic changes because there is no detectable
fibrosis or necrosis while a mild degree of hepatic degeneration.
4- In the case of mice treated with thalidomide reference drug, (30
mg/kg body weight), it was found a centrilobular hepatic necrosis
(arrow), midzonal, and periportal hepatic vacuolation.