Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

doi:10.1007/s40242-017-6330-8

高等学校化学研究 ›› 2017, Vol. 33 ›› Issue (1): 61-69.doi: 10.1007/s40242-017-6330-8

Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

YANG Hongliang¹, XU Guoxing², PEI Yazhong²

1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China;
2. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China

收稿日期:2016-07-29 修回日期:2016-09-07 出版日期:2017-02-01 发布日期:2016-10-24
通讯作者: YANG Hongliang,E-mail:hongl_yang@126.com E-mail:hongl_yang@126.com
基金资助:
Supported by the Youth Natural Science Foundation of Heilongjiang Province, China(No.QC2016025).

Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

YANG Hongliang¹, XU Guoxing², PEI Yazhong²

1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China;
2. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China

Received:2016-07-29 Revised:2016-09-07 Online:2017-02-01 Published:2016-10-24
Contact: YANG Hongliang,E-mail:hongl_yang@126.com E-mail:hongl_yang@126.com
Supported by:
Supported by the Youth Natural Science Foundation of Heilongjiang Province, China(No.QC2016025).

摘要/Abstract

摘要：

A series of novel pyridinyl-4,5-2H-isoxazole derivatives was synthesized and their chemical structures were characterized by ¹H NMR, ¹³C NMR as well as MS spectroscopic methods, their melting points were also determined. The inhibitory effects of them against breast cancer cell line(MCF-7) were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) procedure in vitro. Most of them possesed potent anti-proliferative activities, among which compounds 11c and 11j exhibited half maximal inhibitory concentrations(IC₅₀) of 1.9 and 1.5 μmol/L, respectively. These compounds also exhibited potent anti-proliferative activities against both human hepatoma cell line(HepG2) and cervical cancer cell line(HeLa). Preliminary structure-activity relationship (SAR) information from these compounds can be used to guide further exploration of new compounds with better potency as molecular probes. Further study on the mechanism-of-action of these compounds is under investigation.

关键词: Pyridine, Isoxazole, Anticancer activity, Chemotherapeutic agent

Abstract:

Key words: Pyridine, Isoxazole, Anticancer activity, Chemotherapeutic agent

YANG Hongliang, XU Guoxing, PEI Yazhong. Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents[J]. 高等学校化学研究, 2017, 33(1): 61-69.

参考文献

[1] Devita V. T., Rosenberg S. A., N. Engl. J. Med., 2012, 366(23), 2207
[2] Daly J. M., Weintraub F. N., Shou J., Rosato E. F., Lucia M., Ann. Surg., 1995, 221(4), 327
[3] Kaliberov S. A., Buchsbaum D. J., Cancer Res., 2012, 115, 221
[4] Gerber D. E., Schiller J. H., J. Clin. Oncol., 2013, 31(8), 1009
[5] Zhang Y. H., Ye L. H., Peng H. Y., Zhang X., J. Nanjing Univ. Tradit. Chin. Med., 2011, 1, 4
[6] Flaherty K. T., Clin. Cancer Res., 2006, 12(7), 2366
[7] Kim J., Lee J. E., Lee S. H., Yu J. H., Lee J. H., Park T. G., Hyeon T., Adv. Mater., 2008, 20(3), 478
[8] Demartino J. K., Boger D. L., Drug Future, 2008, 33(11), 969
[9] Ferlay J., Autier P., Boniol M., Heanue M., Colombet M., Boyle P., Ann. Oncol., 2007, 18(3), 581
[10] Nussbaumer S., Bonnabry P., Jean-Luc V., Fleury-Souverain S., Talanta, 2011, 85(5), 2265
[11] Jemal A., Siegel R., Ward E., Murray T., Xu J., Smigal C., Thun M. J., Cancer J. Clin., 2006, 56(2), 106
[12] Kaushik G., Kaushik T., Khanduja S., Pathak C. M., Khanduja K. L., Cancer Lett., 2008, 270(1), 120
[13] Bhuva H. A., Kini S. J., J. Mol. Graph. Model., 2010, 29(1), 32
[14] Albreht T., Mckee M., Alexe D. M., Coleman M. P., Martin-Moreno J. M., Eur. J. Cancer, 2008, 44(10), 1451
[15] Madhusudan S., Trivadi S., Ganesan T. S., Clinical. Biochem., 2004, 37, 618
[16] Sawyers C., Nature, 2004, 432(7015), 294
[17] Eckhardt S., Curr. Med. Chem. Anti-Cancer Agents, 2002, 2(3), 419
[18] Li Q. B., Xu W. F., Curr. Med. Chem. Anti-Cancer Agents, 2005, 5(1), 53
[19] Bagalkot V., Zhang L. F., Levy-Nissenbaum E., Jon S. Y., Kantoff P. W., Langer R., Farokhzad O. C., Nano Lett., 2007, 7(10), 3065
[20] Willmann J. K., Bruggen N. V., Dinkelborg L. M., Gambhir S. S., Nat. Rev. Drug Discov., 2008, 7(7), 591
[21] Dong B., Zhu Y. M., Chin. J. Cancer, 2010, 29(3), 340
[22] Yang H. L., Xu G. X., Bao M. Y., Zhang D. P., Li Z. W., Pei Y. Z., Chem. J. Chinese Universities, 2014, 35(12), 2584
[23] Fanta P. E., J. Am. Chem. Soc., 1953, 75, 737
[24] Altmann E., Aichholz R., Betschart C., Buhl T., Green J., Irie O., Teno N., Lattmann R., Tintelnot-Blomley M., Missbach M., J. Med. Chem., 2007, 50(4), 591
[25] Rogez-Florent T., Meignan S., Foulon C., Six P., Gros A., Bal-Mahieu C., Supuran C. T., Scozzafava A., Frédérick R., Masereel B., Depreux P., Lansiaux A., Goossens J. F., Gluszok S., Goossens L., Bioorg. Med. Chem., 2013, 21(6), 1451
[26] Hartshorn M. J., Murray C. W., Cleasby A., Frederickson M., Tickle I. J., Jhoti H., J. Med. Chem., 2005, 48(2), 403
[27] Badrinarayan P., Sastry G. N., J. Chem. Inf. Model., 2011, 51(1), 115

Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

Synthesis, Preliminary Structure-activity Relationships and Biological Evaluation of Pyridinyl-4,5-2H-isoxazole Derivatives as Potent Antitumor Agents

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