SYNTHESIS AND EVALUATION OF SOME 1, 3 DISUBSTITUTED UREA DERIVATIVE FOR ANTIPROLIFERATIVE ACTIVITY

Cancer is thought to be caused by the interaction between genetic susceptibility and environmental toxins. Based on the DNA changes in cells, proliferating cycle of tumor cells can be divided into 4 phase’s Pre-synthetic phase (Gap 1 phase or G1 phase). Cells chiefly make preparations for the synthesis of DNA.Synthetic phase (S phase). Cells are synthesizing their DNA.Post-synthetic phase (Gap 2 phases or G2 phase). DNA duplication has been finished and they are equally divided to the two of future sub-cells. Mitosis phase (M Phase). Each cell is divided into two sub-cells. Some of these new cells enter the new proliferating cycle, the others become non-proliferating cells. G0 phase cells have proliferation ability but do not divide temporally. When proliferating cells are suffered heavy casualties, G0 phase cells will get into proliferating cycle and become the reasons of tumor recurrence. G0 phase cells are usually not sensitive to antineoplastic drugs, which is the important obstacle to tumor chemotherapy. The antiproliferative activities of these compounds were evaluated against a Cytotoxicity analysis of compounds against leukemia cell line -K562 organism homo sapiens(human) organ bone - marrow .tissue - lymphoblast ,disease - chronic myelogenous leukemia(CML) one human tumor cell lines (K562) by applying the MTT colorimetric assay. The 1, 3-disubstituted urea derivatives show good antiproliferative activity against human cancer cell lines (K562). The hydroxyl groups on the phenyl ring reduced the antiproliferativeactivities. The OH groups could be responsible for a reduction in the permeability of the cell membrane. Generally, an aromatic ring on N-3 seems to be in favor of enhancing the inhibitory activity, compounds introduced a nitro group substituent atC-3 position on the aromatic ring approved to generally decrease activity. Cells were incubated with different concentrations of the extract for 5 days in a 96 well plate, after which the live cells which did not take in stain and dead cells which took in stain were counted. For counting the cell suspension was mixed with an equal volume of trypan blue and was counted. Concentration that inhibited the growth of cells at 50% (IC50) was computed. Substances with low IC50 indicate potential for cytotoxicity. (A) 1, 1-dimethyl-3-phenyl-3-(5-phenyl-1, 3, 4-thiadiazol-2-yl) urea was found higher activity than other 4 - compounds. The synthesized compounds were confirmed by physico-chemical parameters (melting point, TLC) and by IR, NMR, and MASS spectral analysis.Sample-S001 was found most potent comp