目的 为提高熊果酸的抗肿瘤活性及开发抗肿瘤新药,以熊果酸为先导物开展结构修饰和体外抗肿瘤活性评价。方法 在熊果酸C2、C3和C28位进行结构修饰获得其芳苄叉基硝酸酯类衍生物,并运用四甲基偶氮唑蓝(MTT)法测定衍生物对5种人源肿瘤细胞(肝癌HepG-2细胞、乳腺癌MCF-7细胞、肺癌A549细胞、结肠癌HT-29细胞和宫颈癌Hela细胞)的体外抗肿瘤活性。结果 对6个新型芳苄叉基熊果酸硝酸酯类衍生物的结构进行了红外、核磁共振光谱及质谱确证;MTT结果显示衍生物6c对MCF-7细胞的最大半数抑制浓度为(14.48±0.44) μmol·L-1,优于阳性药物顺铂。结论 衍生物6c具有较强的抑制乳腺癌细胞增殖能力,值得深入研究。
Abstract
OBJECTIVE To carry out structure modification of ursolic acid and in vitro anti-tumor activity evaluation to improve the anti-tumor activity of ursolic acid and develop new anti-tumor drugs. METHODS Structural modification at positions C2, C3 and C28 of ursolic acid was performed to obtain arylidene ursolic acid drivatives. The inhibitory effects of arylidene ursolic acid drivatives on the proliferation of five human tumor cell lines(HepG2, MCF-7, A549, HT-29 and Hela) in vitro were detected by MTT assay. RESULTS The structures of six novel arylidene ursolic acid nitrates were confirmed by IR, 1H-NMR, 13C-NMR, and HR MS. The MTT assay results showed that the IC50 of derivative 6c on MCF-7 cells was (14.48±0.44) μmol·L-1, 6c showed higher anti-proliferative activity than cisplatin . CONCLUSION Derivative 6c has strong anti-proliferation ability on MCF-7 tumor cells and is worthy of further investigation.
关键词
芳苄叉基熊果酸硝酸酯 /
MCF-7细胞 /
抗肿瘤活性
{{custom_keyword}} /
Key words
arylidene ursolic acid nitrate /
MCF-7 cell /
antineoplastic activity
{{custom_keyword}} /
中图分类号：
R914
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LONG Y X, LI X, YANG M, et al. Conventional cancer chemotherapy drugs induce cell senescence and senescence-associated inflammatory factors expression . Immunol J (免疫学杂志), 2021, 37(6): 472-480.
[2] OUN R, MOUSSA Y E, WHEATE N J. The side effects of platinum-based chemotherapy drugs: a review for chemists . Dalton Trans, 2018, 47(19): 6645-6653.
[3] QI C, WANG X, SHEN Z R, et al. Anti-mitotic chemotherapeutics promote apoptosis through TL1A activated death receptor 3 in cancer cells . Cell Res, 2018, 28(5): 544-555.
[4] LI L L, LIU Q, ZHANG G Q, et al. Effects of ursolic acid on breast cancer in vitro and its mechanism. Chin J Cancer Prev Treat (中华肿瘤防治杂志), 2020, 27(9): 692-697.
[5] FANG Z Q, GONG Y M, XU H, et al. Effects of ursolic acid on growth, migration and apoptosis of tongue cancer Tca8113 cells and its mechanism . China J Mod Med (中国现代医学杂志), 2020, 30(7): 19-25.
[6] XU H, ZHANG C, GONG Y M, et al. Effect and mechanisms of ursolic acid on proliferation and apoptosis in human tongue cancer cells . Chin J Clin Pharmacol (中国临床药理学杂志), 2020, 36(6): 651-654.
[7] ZHANG M, HE M, SUN Q, et al. Mechanism study on ursolic acid induced apoptosis of colorectal cancer SW480 cells based on Hedgehog signaling pathway. Chin Tradit Herb Drugs (中草药), 2021, 52(8): 2365-2373.
[8] ZONG Y H, HUO L J, CHANG S. Effects of ursolic acid on apoptosis and PI3K/Akt signaling pathway of human hepatoma HepG2 cells . J Med Res(医学研究杂志), 2020, 49(9): 107-111,115.
[9] LEE K C, CHEN Y L, LIN P Y, et al. Ursolic acid-induced apoptosis via regulation of the PI3K/Akt and MAPK signaling pathways in Huh-7 cells . Molecules, 2018, 23(8): 2016. Doi:10.3390/molecules23082016.
[10] KANG D Y, SP N, LEE J, et al. Antitumor effects of ursolic acid through mediating the inhibitong of STAT3/PD-L1 signaling in non-small cell lung cancer cells . Biomedicines, 2021, 9(3): 297. Doi:10.3390/biomedicines9030297.
[11] GUO J L, HAN T, BAO L, et al. Ursolic acid promotes the apoptosis of cervical cancer cells by regulating endoplasmic reticulum stress . J Obstet Gynaecol Res,2019, 45(4): 877-881.
[12] MENG Y Q, XU C D, YU T T, et al. Synthesis and antitumor activity evaluation of ursolic acid derivatives . J Asian Nat Prod Res, 2020, 22(4): 359-369.
[13] YANG X, LI Y, JIANG W, et al. Synthesis and biological evaluation of novel ursolic acid derivatives as potential anticancer prodrugs . Chem Biol Drug Des, 2015, 86:1397-1404. Doi:10.1111/cbdd.12608.
[14] ZHANG T, HE B E, YUAN H, et al. Synthesis and antitumor evaluation in vitro of NO-donating ursolic acid-benzylidene derivatives . Chem Biodivers, 2019,16(6): e1900111. Doi:10.1002/cbdv.201900111.
[15] REN Q Y, NIE B, ZHANG Y J, et al. Functional switch between pharmacophore and directing group and their application in drug discovery and development via C-H activation and functionalization . Chin J Org Chem (有机化学), 2018, 38(10): 2465-2490.
[16] ZHANG J, NIE B, ZHANG Y J. Application and Progress of Organic Synthesis in the Discovery of Innovative Drugs . Chin J Org Chem (有机化学), 2015, 35(2): 337-361.
[17] QU F Z, XIAO S N, WANG X D, et al. Semi-synthesis and anti-tumor activity of novel 25-OCH3-PPD derivatives incorporating aromatic moiety . Bioorg Med Chem Lett, 2019, 29(2): 189-193.
[18] BAECKER D, OBERMOSER V, KIRCHNER E A, et al. Fluorination as tool to improve bioanalytical sensitivity and COX-2-selective antitumor activity of cobalt alkyne complexes . Dalton Trans, 2019, 48(42): 15856-15868.
[19] LIU H R, AHMAD N, LV B, et al. Advances in production and structural derivatization of the promising molecule ursolic acid . Biotechnol J, 2021, 16(11): e2000657. Doi:10.1002/biot.202000657.
[20] XIANG R Q, FAN Y. Advances in anti-tumor effects of ursolic acid and its derivatives . J Pharm Res(药学研究), 2019, 38(2): 63-69.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
广州中医药大学“双一流”与高水平大学学科协同创新团队项目资助(2021xk87)
{{custom_fund}}
PDF(946 KB)
