L-N-(2-噻吩磺酰基)氨基酸乙酯衍生物的合成、结构及抗肿瘤活性

Synthesis,Crystal Structure and Antitumor Activity of α-L-Amino Acid Ester Derivatives

将2-噻吩磺酰基引入α-L-氨基酸乙酯中,设计合成了9种未见文献报道的新化合物N-2-噻吩磺酰基-α-L-氨基酸乙酯和N-2-噻吩磺酰基甘氨酸乙酯。结构经IR、1H NMR、MS和元素分析测试技术得以确证。对化合物3a的单晶进行了X射线晶体结构测定,结果表明,其属于单斜晶系,Cc空间群,晶胞参数a=1.4538(2)nm,b=0.56902(9)nm,c=1.4337(2)nm,Z=4,V=1.0978(3)nm3,Dc=1.508mg/m3,α=90.00°,β=112.245(2)°,γ=90.00°,F(000)=520,R=0.0858,wR=0.2265。经MTT法多次平行实验观测,结果发现,部分目标化合物对白血病K562细胞的增殖有明显的抑制作用:在质量浓度为1.0×10-8g/mL时,化合物3f、3g、3i对白血病K562肿瘤细胞的增殖有较好的抑制作用,抑制率分别为40.22%、33.47%和31.86%,化合物3a～3i对白血病K562肿瘤细胞的增殖的半数抑制质量浓度(IC50,1×10-6g/mL)依次为:35.65、13.87、9.23、4.9、9.24、8.16、7.84、7.73、7.73、6.57。实验中还发现,部分化合物能够诱导肿瘤细胞自然凋亡。通过与5-氟尿嘧啶(5-FU)阳性对照结果表明,该类化合物具有很好的研究开发潜力和价值。

In order to search for new antineoplastic drugs, nine novel N-2-thiophenesulfonyl-α-L-amino-acid esters were synthesized. The structures of the target compounds were determined by means of IR, ^1H NMR, MS and elemental analysis. The crystal structure of the target compound 3a was determined by X-ray diffraction analysis. Crystal data： Monoclinic, space group ： Cc, α = 1. 453 8 （2） nm, b = 0. 569 02 （9） nm, c = 1.4337（2） nm, Z=4, V= 1.097 8（3） nm^3, Dc =1.508 mg/m^3, α =90. 00°, β = 112.245（2）°, γ= 90. 00°, F（000） = 520, R = 0. 085 8, ωR = 0. 226 5. Via MTT assay, the inhibitory rate of the title compounds against the K562 Cell Proliferation was measured. The inhibition rate of the compounds（3f, 3g, 3i） against leukemia K562 cell proliferation were 40. 22% , 33.47% , and 31.86% , respectively, when the concentration of was 1.0 × 10^-8 g/＇mL. The IC50 concentration（ 1 × 10^-6 g/mL） of the compounds（3a -3i） was 35.65, 13.87, 9.23, 4. 9, 9.24, 8. 16, 7. 84, 7.73, 7.73, and 6. 57, respectively. The result of preliminary bioassay shows that some of the target compounds possess antiproliferation effects on K562 cells. Some of the comoounds induced cell apoptosis in the experiment.