Design,Synthesis,and Preliminary Anti-tumor Activity Studies of Novel 1,2-Disubstituted Hydrazines
Thirteen 1,2-disubstituted hydrazines,including ten 2-aryl-1-(4-(N-isopropyl)aminoformyl)benzyl hydrazines(9a～9j),two 2-aryl methylene-1-(4-(N-isopropyl)aminoformyl)benzyl hydrazines(13a～13b),and 2-(4-methyl)benzoyl-1-(4-(N-isopropyl)aminoformyl)benzyl hydrazine(14)have been designed and synthesized.By employing methyl thiazolyl tetrazolium(MTT)assay,generally all the title compounds were shown with better anti-cancer activity against rat glioma cells(C6),mouse melanoma cells(K1735),human liver cancer cells(HepG-2),human colon cancer cells(SW620),human breast cancer cells(MDA-MB-231),and human malignant melanoma cells(A357)than the positive procarbazine(Pcb).It was demonstrated that Pcb is sensitive to murine melanoma cells(B16).However,under the condition of 48-hour incubation,9a,9b,and 9i were confirmed more active against B16 cells than Pcb.More interestingly,9a was the most active anti-cancer agent against the five cancer cell lines except both C6 and SW620 cell lines among the 13 title compounds,its IC50 value against MDA-MB-231 cells was(10.8±0.9)μmol/L,whilst 13b was the most active against C6 cells with IC50 value of(15.9±3.1)μmol/L,and 9e was the most active against SW620 cells with IC50 value of(62.7±1.4)μmol/L.It was found that when the substituent in aryl group of 9a～9j was electron-withdrawal,the anti-cancer activity of compound with substituent at me-ta-position was better that at para-position(9g＞9f,9i＞9h).Intriguingly,when the substituent was an electron-donor group,this law was lost.It was also identified that the anti-cancer activity against SW620 cells will be enhanced with the existence of a weak electron-donor inductive group.Mouse embryonic fibroblasts(3T3)were applied here.Compounds 9a,9b,13a,and 13b were displayed sensitive to this cell line.IC50 values of 9a,and 13a were(24.9±1.2),and(13.9±1.7)μmol/L,respec-tively.
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