Chinese Journal of Organic Chemistry >
Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives
Received date: 2018-03-29
Revised date: 2018-05-06
Online published: 2018-06-06
Supported by
Project supported by the Guizhou Science Technology Program (No. 20161055), the Young Talents Scientific Research Foundation of Guizhou Education Department (No. KY[2017]115), and the State Key Laboratory of Functions and Applications of Medicinal Plants (No. FAMP201707K).
A series of novel 1,3-disubstituted-indol-2-one derivatives containing 1,3,4-thiadiazole, thioether and amide moiety were designed and synthesized based on 2,3-dioxindole (isatin). The inhibition activities of all the target compounds against several cancer cell lines were evaluated via thiazolyl blue tetrazolium bromide (MTT) assay method. The preliminary bioassay results indicated that all of the title compounds exhibited a certain antitumor activity in vitro against human liver cancer cell line (HepG2), human transfer of pancreatic cancer cell line (AsPc-1) and human cervical cancer cell line (Hela). The IC50s values of N-(5-((2-fluorobenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)propanamide (6l) [(11.47±0.01), (2.43±0.05), (1.91±0.06) μmol/L, respectively] and N-(5-((2-methylbenzyl)thio)-1,3,4-thiadiazol-2-yl)-3-(2-oxo-3-(p-tolylimino)indolin-1-yl)-propanamide (6p) [(14.32±0.01), (1.61±0.04), (2.77±0.05) μmol/L, respectively] against HepG2, AsPc-1 and Hela cell lines were lower than that of control gefitinib [(16.41±0.05), (5.19±0.02), (7.89±0.05) μmol/L, respecti-vely].
Key words： indol-2-one derivatives; thiadiazole; thioether; amide; antitumor activity
Tian Kun , Meng Jiao , Gan Yiyuan , Li Xiaoqin , Wu Shouqun , Chen Jie , Li Wen , Qi Yayun , Hu Weinan , Wang Zhenchao , Ouyang Guiping . Design, Synthesis and Antitumor Activity Evaluation of 1,3,4-Thia-diazole, Thioether and Amide Based 1,3-Disubstituted-indol-2-one Derivatives[J]. Chinese Journal of Organic Chemistry, 2018 , 38(10) : 2657 -2665 . DOI: 10.6023/cjoc201803051
[1] Ali, A. Q.; Teoh, S. G.; Salhin, A.; Eltayeb, N. E.; Khadeer Ahamed, M. B.; Abdul Majid, A. M. S. Spectrochim. Acta A 2014, 125, 440.
[2] Tian, W. Y.; Xu, S.; Liang, Z. W.; Sun, D. L.; Zhang, R. H. Chin. J. Org. Chem. 2016, 36, 2121(in Chinese). (田文艳, 徐松, 梁中卫, 孙德立, 张荣华, 有机化学, 2016, 36, 2121.)
[3] Ma, J. J.; Bao, G. L.; Wang, L. M.; Li, W. T.; Xu, B. X.; Du, B. Q.; Lv, J.; Zhai, X.; Gong, P. Eur. J. Med. Chem. 2015, 96, 173.
[4] Capdevila, J.; Carrato, A.; Tabernero, J.; Grande, E. Crit. Rev. Oncol. Hemat. 2014, 92, 83.
[5] Young, B. L.; Cooks, R. G.; Madden, M. C.; Bair, M.; Jia, J.; Aubry, A. F.; Miller, S. A. J. Pharm. Biomed. Anal. 2007, 43, 1602.
[6] Best, L.; Brown, P. D.; Sener, A.; Malaisse, W. J. Eur. J. Pharmacol. 2010, 629, 159.
[7] Gao, W. T.; Zhao, P. B.; Zhao, B. B.; Li, Y. Chin. J. Org. Chem. 2014, 34, 126(in Chinese). (高文涛, 赵鹏波, 赵宾宾, 李阳, 有机化学, 2014, 34, 126.)
[8] Liu, J. W.; Zhao, M.; Qian, K. D.; Zhang, X. Y.; Lee, K. H.; Wu, J. H.; Liu, Y. N.; Peng, S. Q. Bioorg. Med. Chem. 2010, 18, 1910.
[9] Senwar, K. R.; Naidu, V. G. M.; Srinivasulu, G.; Shankaraiah, N. Eur. J. Med. Chem. 2016, 118, 34.
[10] Li, J. R.; Wu, N.; Tian, Y. X.; Zhang, J. J. and Wu, S. G. A. Med. Chem. Lett. 2013, 4, 806.
[11] Cutignano, A.; Bifulco, G.; Bruno, I.; Casapullo, A.; Dragmacidin, F. Tetrahedron 2000, 56, 3743.
[12] Li, P.; Yang, B. l.; Hao, F.; Wang, P.; He, H. y.; Huang, L. Bioorg. Med. Chem. Lett. 2016, 26, 3346.
[13] Picazo, E.; Giordanetto, F. Drug Discovery Today 2015, 20, 277.
[14] Abdel-Rahman, A. H.; Keshk, E. M.; Hanna, M. A.; El-Bady, S. M. Bioorg. Med. Chem. 2004, 12, 2483.
[15] Michael, B. P.; Podoll, J. D.; Marholz, L. J.; Wang, X. Bioorg. Med. Chem. Lett. 2014, 24, 5602.
[16] Rajanarendar, E.; Ramakrishna, S.; Govardha, R. K.; Nagaraju, D.; Reddy, Y. N. Bioorg. Med. Chem. Lett. 2013, 23, 3954.
[17] Svetlana, F.; Elinor, N. B.; Shani, Z.; Michal, W.; Abraham, N.; Marta, W. Bioorg. Med. Chem. Lett. 2014, 24, 2283.
[18] Virgolini, I.; Fitscha, P.; Rauscha, F.; Sinzinger, H. Prostaglandins Leukotrienes Essent. Fatty Acids 1990, 40, 125.
[19] Ablimit, A.; Zhang, Y. H.; Zhang, Z. P.; Liu, C. J. Chin. J. Org. Chem. 2016, 36, 875(In Chinese). (阿布力米提·阿布都卡德尔, 张永红, 张增鹏, 刘晨江, 有机化学, 2016, 36, 875.)
[20] Wagdy, M. E.; Mohamed, F.; Hany, S. I.; Mohamed, H. A.; Suher Z.; Mamdouh, M. A.; Sahar, M. A.; Hatem, A. A.; Dalal, A. A. Eur. J. Med. Chem. 2015, 100, 89.
[21] Ibrahim, H. S.; Abou, S. S. M.; Ismail, N. S. M.; Ismail, N. S. M.; Elaasser, M. M.; Aly, M. H.; Abdel, A. H. A. Eur. J. Med. Chem. 2016, 108, 415.
[22] Davidovich, P.; Aksenova, V.; Petrova, V.; Tentler, D.; Orlova, D.; Smirnov, S.; Gurzhiy, V.; Okorokov, A. L.; Garabadzhiu, A.; Melino, G.; Barlev, N.; Tribulovich, V. ACS Med. Chem. Lett. 2015, 6, 856.
[23] Vudhgiri, S.; Koude, D.; Veeragoni, D. K.; Misra, S.; Prasad, R. B. N.; Jala, R. C. R. Bioorg. Med. Chem. Lett. 2017, 27, 3370.
[24] Jakovljevic, K.; Matic, I. Z.; Stanojkovic, T.; Krivokuca, A.; Markovic, V.; Joksovic, M. D.; Mihailovic, N.; Niciforovic, M.; Joksovic, L. Bioorg. Med. Chem. Lett. 2017, 27, 3709.
[25] Shen, L. H.; Li, H. Y.; Shang, H. X.; Tian, S. T.; Lai, Y. S.; Liu, L. J. Chin. Chem. Lett. 2013, 24, 299.
[26] Patil, V.; Shinde, O.; Asrondkar, A.; Bobade, A. S.; Chowdhary, A. S. IOSR J. App. Chem. 2014, 7, 10.
[27] Cardoso, A. L.; Sousa, C.; Marta, S. C. H.; José A. P.; Teresa M. V. D. Molecules 2015, 20, 22351.
[28] Karthikeyan, C.; Solomon, V. R.; Lee, H.; Trivedi, P. Biomed. Prev. Nutr. 2013, 3, 325.
/
| 〈 |
|
〉 |
