Abstract：OBJECTIVE To design and synthesize N-hydroxy-5-(3-substituted urea)-1H-indole-2-amide derivatives and investigate their anti-tumor activity in vitro. METHODS A series of new N-hydroxy-5-(3-substituted ureido)-1H-indole-2-carboxamide derivatives (7a-7n)were designed and prepared from p-nitrophenylhydrazine and ethyl pyruvate. Their antitumor activities against Hela (breast cancer) lines, cervical cancer cell (MCF7) and human hepatoma cell lines (HepG2) were evaluated by methyl thiazolyl (MTT) method. RESULTS Target compounds indicated certain antitumor activities,especially compound 7h showed the strongest cytotoxicity to Hela cells with a half inhibition concentration (IC50) of 7.31 μmol·L-1. CONCLUSION The series of compounds show preferable antitumor activities, which are worthy of further study.
JEMAL A, BRAY F, CENTER M M, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2):69-90.
[2]
LIU S Y,DAI J J,YOU J, et al. Syntheses and anticancer evaluations of novel 3, 5 -disubstituted-1H-indole derivatives. Chemistry(化学通报),2018, 81(5):456-460.
[3]
NEIDLE S. Cancer Drug Design and Discovery(抗肿瘤药物设计与发现). 2nd ed.Beijing:Chemical Industry Press, 2017.
[4]
YANG Y X, ZANG S J, LENG A L, et al. Analysis of the proportion of drug expenses and medical insurance payment based on hospitalization expenses of five cancer patients . J Shangdong Univ (Health Sci)(山东大学学报:医学版),2019, 57(4):113-118.
[5]
KULKE M H, LENZ H J, MEROPOL N J, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol, 2008, 26(20):3403-3410.
[6]
BURSTEIN H J, ELIAS A D, RUGO H S, et al. Phase Ⅱ study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol, 2008, 26(11):1810-1816.
[7]
ANDREANI A, BURNELLI S, GRANAIOLA M. Antitumor activity of bis-indole derivatives. J Med Chem, 2008, 51(15):4563-4570.
[8]
MAHMOUD K H, WERSIG T, SLYNKO I, et al. Novel inhibitors of breast cancer relevant kinases Brk and HER2. Med Chem Commun, 2014, 5(5):659-664.
[9]
WU Z, FANG M J, QIN J B, et al. N-substituted-5-((4-substituted pyrimidine-2-yl)amino)indole derivative as well as preparation method and purpose thereof:China, CN201710950061.8 . 20180227. WATTERSON S H, LIU Q J, BERTRAND M B, et al. Discovery of branebrutinib(BMS-986195):a strategy for identifying a highly potent and selective covalent inhibitor providing rapid in vivo inactivation of Bruton'styrosine kinase(BTK). J Med Chem, 2019, 62(7):3228-3250. ZHANG C, XU D, WANG J, et al. Efficient synthesis and biological activity of novel indolederivatives as VEGFR-2 tyrosine kinase inhibitors. Russ J Gen Chem, 2017, 87(12):3006-3016. FAN D C, SUN W Z, QIU P J, et al. Exploring stereoselectivity of 3-indolyl cyclopentindoles: a parallel synthesis and anti-EGFR study on human cancer cells. Eur J Med Chem, 2014, 74(3):533-540. LIN Y T,WANG Y F,YANG J C H, et al. Development of renal cysts after crizotinib treatment in advanced ALK-positive non-small-cell lung cancer. J Thorac Oncol,2014,9(11):1720-1725. CHEN J Y, ZHOU Y L, WANG S M, et al. Indoloquinolone compounds as anaplastic lymphoma kinase(ALK) inhibitors:China, CN201480076401.3 . 20170222. WANG Y D, WU C J, LI N, et al. Progress in the research of PARP-1 inhibitors as antitumor agents. Chin J Med Chem(中国药物化学杂志),2016, 26(3):253-262. HU H Y, LIN C R, AO M T, et al. Synthesis and biological evaluation of 1-(2-(adamantane-1-yl)-1H-indol-5-yl)-3-substituted urea/thiourea derivatives as anticancer agents. Rsc Adv, 2017, 7(81):51640-51651. KINNAIRD A, ZHAO S, WELLEN K E, et al. Metabolic control of epigenetics in cancer. Nat Rev Cancer, 2016, 16(2):694-707. WILKO W, ANNIKA R, VOLKER G, et al. Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer:a retrospective analysis. Lancet Oncol, 2008,9(2):139-148. HU H Y, WU J, AO M T, et al. Synthesis, structure-activity relationship studies and biological evaluation of novel 2,5-disubstituted indole derivatives as anticancer agents. Chem Biol Drug Des,2016, 88(7):766-778. YASUKA W, NAO K, KUWA T, et al. Copper-catalyzed pyrrole synthesis from 3,6-dihydro-1,2-oxazines. Green Chem, 2018, 20(19):4409-4413.
2020, Vol. 55 
