Easmon, Johnny published the artcileSynthesis, Cytotoxicity, and Antitumor Activity of Copper(II) and Iron(II) Complexes of 4N-Azabicyclo[3.2.2]nonane Thiosemicarbazones Derived from Acyl Diazines, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone, the main research area is antitumor copper iron thiosemicarbazone complex synthesis Burkitt lymphoma.
A series of thiosemicarbazones (TSCs) (bearing a 4N-azabicyclo[3.2.2]nonane moiety) derived from 3-acylpyridazines, 4-acetylpyrimidines, and 2-acetylpyrazines were synthesized as potential antitumor agents. TSCs exhibited potent cytotoxic activity against human acute lymphoblastic leukemia CCRF-CEM cells (IC = 0.05-0.77 M) and colon adenocarcinoma HT-29 cells (IC = 0.011-2.22 M). Copper II complexes of TSCs showed significant improvement in cytotoxic activity against HT-29 cells (IC50 = 0.004-1.51 μM) by a factor of 3. However, complexation of some TSC ligands with Fe(II) results in lowering of cytotoxic activity by a factor of 7. In clonogenic assays involving human tumor cells of different tumor origins, three of the TSCs and their copper complexes exhibited remarkable cytotoxic activities with mean IC50 values of 6, 0.18, 1, 1, 0.37, and 0.37 nM, resp. In particular, the compounds were highly effective against human colon carcinoma and large and small cell lung carcinoma cells. One of the TSC derivative was evaluated in vivo in nude mice bearing LXFL 529 human large cell lung carcinoma cells. With respect to antitumor activity, application of 30 mg/kg/d resulted in moderate inhibition (42%) of tumor growth. No effect on tumor growth was observed at a dose of 10 mg/kg/d. However, a dose of 40 or 60 mg/kg/d resulted in 50 and 75% death, resp., in the treated mice, indicating the high toxicity of these compounds Using human liver microsomes, one of the TSC compound was rapidly and highly metabolized in vitro. In actual fact, only 2% of the unmetabolized compound could be detected in the incubation medium after 5 min. The IC50 for cell proliferation (0.006-0.022 μM) elicited by these compounds is much lower than that of the inhibition of [14C]cytidine incorporation into DNA (0.18-3.32 μM). These compounds are also non-cell cycle specific agents. Interestingly, three of these compounds were potent inducers of apoptosis in Burkitt’s lymphoma cells.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 67073-96-5 belongs to class pyrimidines, name is 1-(6-Methylpyrimidin-4-yl)ethanone, and the molecular formula is C7H8N2O, Recommanded Product: 1-(6-Methylpyrimidin-4-yl)ethanone.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia