الفهرس 
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Abstract
Heterocyclic compounds have a large spectrum of biological activities
including antitumor activity, thiazole derivatives are a category of those
compounds that has proven a considerable antitumor and antioxidant activities.
Objective: the essential objective of this research is to prove the antitumor and
antioxidant activity of 2 newly prepared compounds of 2,5- disubstituted thiazole
up on EAC bearing mice and many kinds of human cancer cell lines.
The first compound (TD1) is:- 5-p-(chlorophenyl)-2-(2,3-dihydroxybenzylidene
amino thiazole). And the second compound is (TD2) 5-(p-chlorophenyl)-2-
[(benzo [5,6]-coumarin-3-yelthylidene) amino thiazole.
Materials and Methods: Antitumor activity of TD1 and TD2 was examined
firstly on many kinds of human cancer cell lines as HCT116 (colon cancer),
MCF-7 (breast cancer), HEPG2 (liver cancer) and PC3 (prostate cancer), IC50 for
each compound was determined. Then the antitumor activity of TD1 and TD2
was examined on EAC in Swiss albino Mice, the effective doses were selected
after dose response curve experiment was done at doses of 5 mg/kg for TD1 and
2.5 mg/kg for TD2. After transplantation of tumor, TD1 and TD2 were
administrated for 10 consecutive days (day after day). After one day of last dose
and 18 hours of fasting, 7 mice were sacrificed and the remaining was kept alive
to evaluate ILS %. Antitumor activity of TD1 and TD2 was assessed by
inspecting tumor volume, tumor weight, viable cell count, hematological,
biochemical, histological, antioxidant and apoptotic parameters of mice.
Results: Treatment of EAC tumor bearing mice with TD1 and TD2 at doses of 5
and 2.5 mg/kg respectively significantly decreased the body weight, tumor
volume, tumor weight, and viable tumor cell count .TD1 and TD2 significantly
increases the life span of the EAC treated mice.
Similarly, in the present study reduced hemoglobin, RBC count and WBC count
was observed in EAC control group, RBCs count was increased in TD1 and TD2
groups while hemoglobin concentration was decreased in TD1 group and increased in TD2 group as compared to EAC control group. In addition,
administration of TD1 and TD2 raised WBCs count compared to EAC control
group.
Concerning biochemical parameters, values of SGPT, SGOT, and ALB. were
elevated in the EAC control group but lowered in TD1 &TD2 groups. TGL also
was lowered in drug groups. TD1 and TD2 treatment also decreased the levels of
MDA and raised the values of GSH, Catalase and SOD .
TD1 &TD2 treatment prevent the decrease of antioxidant levels and rise in MDA
levels in EAC bearing mice which prove the potency of TD1 &TD2 in protecting
against oxidative stress by normalization of antioxidants values in EAC bearing
mice.
The histopathology inspection of the liver & kidney of EAC control mice has
shown many abnormalities in comparing with normal one, Modulation of those
effects ,which have been noticed in TD1 & TD2 treated mice proved the strong
antioxidant and hepatoprotective effects of the compounds. Flow cytometric
analysis has shown that Arrest of cell cycle mostly occur in S phase then lead to
apoptosis . Flow cytometric examination of P53 has shown increasing in the
percentage of +ve population in treated group than control group (approximately
double increase).
Conclusion: from the above mentioned results, It was concluded that TD1 and
TD2 has a high antitumor & antioxidant activity against Ehrlich ascites carcinoma
in mice and human cancer cell lines.