الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 113 |  |  |
| | | from | 113 | | |
Abstract
Tumors, both benign and malignant, are well-known refractory diseases. Efforts trying to overcome this millennium problem and many new chemical drugs have been developed. Although these drugs currently available are favorable in alleviation of the condition and adjuvant chemotherapy, most of them have a limited application because of their less well effectiveness, severe toxicity, and high manufacturing cost. Chalcones are pharmacologically active compounds, chemically known as derivatives of 1,3-diphenylprop-2-en-1-one and shows potential biological activities. Chalcones have increased the chemotherapy of the Alzheimer’s disease treatment owing to their ability to inhibit the primary enzyme in Alzheimer’s disease. In the treatment of gastrointestinal syndromes, chalcone has registered its presence following the findings that some chalcone inhibits enterocolitica tyrosine phosphate a primary target for therapeutic intervention against disease provoked by Yersinia. Some chalcones have been reported to selectively inhibit COX-2 over COX-1 making them a better anti-inflammatory with less adverse effect than the classical NSAIDs which selectively inhibit COX-1 over COX-2. Chalcones have also been reported to show excellent inhibition of lipoxygenase, making this class of compound good antioxidant agent. Other chalcones are used as inhibitors of the suppressor protein P53, blockers of nitric oxide production or inhibitors of cytochrome P450 enzymes. Many investigations have shown the advantageous activities and multifarious mechanisms of flavonoids. Chalcones (1,3-diaryl-2-propen-1- ones) are a kind of open chain flavonoids, which makes their structures more diversified than other types. Chalcones were proved to have Chapter 6 - 58 - Summary and Conclusion antitumor potential either in vitro or in vivo, and a large proportion of underlying mechanisms have been explained. Based on the current studies, chalcones are highly multifunctional and their targets cover almost all of the actions of tumor cells, including growth, proliferation. Several chalcones showed significant antitumor activity both in vitro and in vivo, such as xanthohumol, isoliquiritigenin and butein. These chalcones can be served as promising lead compounds for further drug development. However, it should also be noted that much of the pharmacological potential of chalcones is still not utilized due to some unclear mechanisms, and more working such as fundamental and clinical researches should be done to make best use of these natural products. In the present study, the antitumor activity and immunomodulatory effect of synthetic chalcones and metal complexes was investigated in tumor bearing mice. The study was conducted on two types of chalcones I and II, the data showed that the type I was more potent anticancer agent than II against Ehrlich ascetic carcinoma cells in vivo. This findings was addressed by determining the tumor profile of the collected ascetic fluid from groups of mice under study and when compared to cisplatin as a reference drug. Results were statistically analyzed and can be summarized as the following: characterization of the solid complexes: The analytical data of the isolated solid complexes are in agreement with the proposed structure. The solid complexes were found to be stable in air and soluble in most organic solvents. The IR spectrum measurement: The free chalcone ligand, the band occurring at 1675 cm-1 due to (υ) C=O shift (1631 cm1) in complex indicating the participation of the oxygen atom of the carbonyl group in Chapter 6 - 59 - Summary and Conclusion complex formation. The streatching vibration of the (υ) C=N linkage of the pyridine ring at 1496 cm-1 in free chalcone was shifted to lower or higher frequency (1518 cm-1) indicating the participation of C=N in complex formation. Tumor profiling: Treatment with chalcone I increased the number of dead cells and decreased the number of live cells compared to tumor bearing mice alone. However, treatment with chalone II did not showed a significant reduction in the number of the live and dead tumor cells as compared to their control. Tumor cell cycle analysis: Similar patten of cell cycle were observed in mice which were treated with chalcone I and non-treated tumor bearing mice. Treatment with chalcone I, the G1, S and G2 phase in tumor cells harvested from groups of mice which treated with cisplatin or treated with chalcone I showed significant decrease. Detection of CD8 %: The highest percentage of CD8 T-cells was found in the peripheral blood (PBL) of the group of mice which inoculated with EAC-cells and treated with chalcone I. The lowest expression of CD69 marker was reported on the CD8 T-cells harvested form the group of mice which inoculated with EAC-cells and treated with chalcone I. Differential lymphocytes and monocytes %: The percentage of lymphocytes did not changed in all groups under the study, while the monocytes was increased in the EAC-bearing mice alone and EACbearing mice treated either with cisplatin or with chalcone I. the percentage of monocytes did not change in the group of mice which inoculated with EAC-cells and treated with chalcone II when compared to the control.