Search

As 17β-estradiol and its derivatives have good affinity with estrogen receptors and have unique antitumor properties, O1-propargyl-N4,N4-bis(2-chloroethyl)-4-aminophenol and N4,N4-dipropargyl-N1,N1-bis(2-chloroethyl)-1,4-phenylenediamine were respectively combined with 17β-estradiol through linkers of different lengths. These targeted novel nitrogen mustard 17β-estradiol derivatives were tested antiproliferative activity using the MTT assay. The results illustrated that these compounds were less toxicity to HL-7702 (human liver cells) and SKOV-3, though all their activity potency was moderate or weak aganist the MDA-MB-231, MCF-7 and BEL-7404 cell lines. The inhibitory activity of the O1-propargyl-N4,N4-bis (2-chloroethyl)-4-aminophenol derivatives (compounds III-1~6 and VII-1~4) were obviously better than the N4-dipropargyl-N1, N1-bis (2-chloroethyl) -1,4-phenylenediamine derivatives (compounds IV-1~6 and VIII-1~4) against tested tumor cell lines. And three hybrids (compounds III-2, III-6, and VII-3) exhibited good inhibitory activity against BEL-7404 cell line (IC50 = 13.5, 15.3 and 13.9 μM, respectively). After that, we performed KEGG pathway analysis on compound III-6, and the results showed that III-6 mainly induced breast cancer cell apoptosis by regulating the expression of the proteins in NF-κ B pathway. [ABSTRACT FROM AUTHOR]