Structurally Diverse HIV-1 Integrase Inhibitors: Past,Present and Perspective

Chinese Journal of Organic Chemistry ›› 2004, Vol. 24 ›› Issue (11): 1380-1388. Previous Articles Next Articles

结构多样的HIV-1整合酶抑制剂:过去、现在和未来

姜晓华, 龙亚秋^*

中国科学院上海药物研究所合成化学实验室上海 201203

收稿日期:2004-02-09 修回日期:2004-03-23 接受日期:2004-04-12 发布日期:2022-09-21
通讯作者: ^* E-mail: yqlong@mail.shcnc.ac.cn; Fax: 86-21-50806876.
基金资助:
国家自然科学基金(Nos. 30200351, 20372068)资助项目.

Structurally Diverse HIV-1 Integrase Inhibitors: Past,Present and Perspective

JIANG Xiao-Hua, LONG Ya-Qiu^*

Laboratory of Medicinal Chemistry, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Shanghai 201203

Received:2004-02-09 Revised:2004-03-23 Accepted:2004-04-12 Published:2022-09-21

Abstract

HIV-1 integrase is an essential enzyme for retroviral replication. It is involved in the integration of HIV DNA into host chromosomal DNA and appears to have no functional equivalent in human cells. Therefore it is an attractive and rational target for selective anti-AIDS therapy. During the past 10 years a plethoraof inhibitors have been identified and some were shown to be selective against IN and block viral replication. The two most predominant classes of inhibitors have been the catechol containing hydroxylated aromatics and more recently the diketoacid containing aromatics. Herein, a review is presented on different categories of compounds that have been studied for the inhibition of the HIV-1 integrase to develop anti-HIV agents. These compounds are: oligonucleotides, curcuminanalogues, polyhydroxylated aromatic compounds, diketo acids, caffeoyl- and galloyl-based compounds. For all these compounds, the important structural features essential for the inhibition of the integrase are pointed out.

Key words: HIV-1 integrase, inhibitor, β-diketoacid, antiviral agent

Cite this article

JIANG Xiao-Hua, LONG Ya-Qiu. Structurally Diverse HIV-1 Integrase Inhibitors: Past,Present and Perspective[J]. Chinese Journal of Organic Chemistry, 2004, 24(11): 1380-1388.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

References

1 Badary, O. Saudi Pharm. J. 1999, 7, 77.
2 Craigie, R. J. Biol. Chem. 2001, 276,23213.
3 Marchand, C.; Zhang, X.-C.; Pais, G. C.; Cowansage, K.; Neamati, N.; Burke, T. R.; Pommier, Y. J. Biol. Chem. 2002, 277, 12596.
4 (a) LaFemina, R. L.; Schneider, C. L.; Robbins, H. L.; Callahan, P. L.; LeGrow, K.; Roth, E.; Schleif, W. A.; Emini, E. A. J. Virol. 1992, 66, 7414.
(b) Esposito, D.; Craigie, R. Adv. Virus Res. 1999,52, 319.
5 Young, S. D. Curr. Opin. Drug Discovery Dev. 2001, 4, 402.
6 Mauri, C.; Bailly, F.; Cotelle, P. Curr. Med. Chem. 2003, 10, 1795.
7 Neamati, N.; Marchand, C.; Pommier, Y. Adv. Pharmacol. 2000, 49, 147.
8 Pommer, Y.; Marchand, C.; Neamati, N. Antiviral Res. 2000, 47, 139.
9 Neamati, N. Expert Opin. Ther. Pat. 2002, 12, 709.
10 Mazumder, A.; Neamati, N.; Sommadossi, J. P.; Gosselin, G.; Schinazi,R. F.; Imbach, J. L.; Pommier, Y. Mol. Pharmacol. 1996, 49, 621.
11 Jing, N.; Hogan, M. E. J. J. Biol. Chem. 1998, 273, 34992.
12 Puras-Lutzke, R. A.; Eppens, N. A.; Weber, P. A.; Houghten, R. A.;Plasterk, R. H. Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 11456.
13 Krajewski, K.; Long, Y.-Q.; Marchand, C.; Pommier, Y.; Roller, P. P.Bioorg. Med. Chem. Lett. 2003, 13, 3203.
14 (a) Singh, S. B.; Jayasuriya, H.; Salituro, G. M.; Zink, D. L.; Shafiee, A.; Heimbuch, B.; Silverman, K. C.; Lingham, R. B.; Genilloud, O.; Teran,A.; Vilella, D.; Felock, P.; Hazuda, D. J. Nat. Prod. 2001, 64, 874.
(b) Matsuzaki, K.; Ogino, T.; Sunazuka, T.; Tanaka, H.; Omura, S.J. Antibiot. (Tokyo) 1997, 50, 66.
(c) Singh, S. B.; Jayasuriya, H.; Hazuda, D. L.; Felock, P.; Homnick, C. F.; Sardana, M.; Patane, M. A. Tetrahedron Lett. 1998, 39, 8769.
15 Long, Y.-Q.; Song, L.-D.; Neamati, N. In Peptides: Biology and Chemistry. Proceedings of the 7th Chinese Peptide Symposium, Eds.: Du,Y.-C.; Zhang, Y.-S.; Tam, J. P., Shanghai Scientific and Technical Publisher,Shanghai, 2004, pp. 89～90.
16 Burke, T. R.; Mazumder, A.; Mazumder, A.; Wang, J.; Carothers, A. M.;Grunberger, D.; Driscoll, J.; Kohn, K.; Pommier, Y. J. Med. Chem. 1995, 38, 4171.
17 Zhao, H.; Neamati, N.; Hong, H.; Mazumder, A.; Wang, S.; Sunder, S.;Milne, G. W. A.; Pommier, Y.; Burke, T. R., Jr. J. Med. Chem. 1997, 40, 242.
18 Reinke, R. A.; King, P. J.; Victoria, J. G.; McDougall, B. R.; Ma, G.; Mao, Y.; Reinecke, M. G.; Robinson, W. E. J. Med. Chem. 2002,45, 3669.
19 Pluymers, W.; Neamati, N.; Pannecouque, C.; Fikkert, V.; Marchand, C.;Burke, T. R.; Pommier, Y.; Schols, D.; DeClercq, E.; Debyser, Z.; Witvrouw, M.Mol. Pharmacol. 2000, 58, 641.
20 Zhao, H.; Neamati, N.; Sunder, S.; Hong, H.; Wang, S.; Milne, G. W. A.; Pommier, Y.; Burke, T. R., Jr. J. Med. Chem. 1997, 40, 937.
21 Zhao, H.; Neamati, N.; Mazumder A.; Sunder, S.; Pommier, Y.; Burke, T.R., Jr. J. Med. Chem. 1997, 40, 1186.
22 (a) Espeseth, A. S.; Felock, P.; Wolfe, A.; Witmer, M.; Grobler, J.; Anthony, N.; Egbertson, M.; Melamed, J. Y.; Young, S.; Hamill, T.; Cole, J. L.; Hazuda, D. J. Proc. Natl. Acad. Sci. U. S. A. 2000, 97,11244.
(b) Marchand, C.; Zhang, X.; Pais, G. C. G.; Cowansage, K.; Neamati, N.; Burke, T. R., Jr.; Pommier, Y. J. Biol. Chem. 2002, 277, 12596.
23 Hazuda, D. J.; Felock, P.; Witmar, M.; Wolfe, A.; Stillmock, K.; Robler, J. A.; Espeseth, A.; Gabryelski, L.; Schleif, W.; Blau, C.; Miller, M. D. Science 2000, 287, 646.
24 Wai, J. S.; Egbertson, M. S.; Payne, L. S.; Fisher, T. E.; Embrey, M. W.; Tran, L. O.; Melamed, J. Y.; Langford, H. M.; Guare, J. P., Jr.; Zhuang, L.;Grey, V. E.; Vacca, J. P.; Holloway, M. K.; Naylor-Olsen, A. M.; Hazuda, D. J.;Felock, P. J.; Wolfe, A. L.; Stillmock, K. A.; Schleif, W. A.; Gabryelski, L. J.; Young, S. D. J. Med. Chem. 2000, 43, 4923.
25 Fujishita, T.; Yoshinaga, T. WO 9950245, 1999 [Chem. Abstr. 1999, 131, 271806].
26 Fujishita, T.; Yoshinaga, T.; Sato, A WO 0039086, 2000 [Chem. Abstr. 2000, 133, 89529].
27 Pais, G. C.; Zhang, X.; Marchand, C.; Neamati, N.; Cowansage, K.; Svarovskaia, E. S.; Pathak, V. K.; Tang, Y.; Nicklaus, M.; Pommier, Y.; Burke, T. R., Jr. J. Med. Chem. 2002, 45, 3184.
28 Zhuang, L.; Wai, J. S.; Embery, M. W.; Fisher, T. E.; Egbertson, M. S.; Payne, L. S.; Guare, J. P.; Vacca, J. P.; Hazuda, D. J.; Felock, P. J.; Wolfe, A.; Stillmock, K. A.; Witer, M. V.; Moyer, G.; Schleif, W. A.; Gabryelski, L.J.; Leonard, Y. M.; Lynch, J. J., Jr; Michelson, S. R.; Yong, S. D. J. Med. Chem. 2003, 46, 453.
29 Long, Y.-Q.; Jiang, X.-H.; Dayam, R.; Sanchez, T.; Shoemaker, R.; Sei, S.; Neamati, N. J. Med. Chem. 2004, 47, 2561.
30 Jiang, X.-H.; Song, L.-D.; Long, Y.-Q. J. Org. Chem. 2003, 68, 7555.

[1]	Zhangyang Shen, Yujie Li, Yimeng Zhao, Yayuan Deng, Yawen Guo, Yu Wang, Yanping Liu, Yanhui Fu. A New Prenylated Isoflavone from the Stems of Harrisonia perforata [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 771-776.
[2]	Huan Xu, Hongfei Wu, Xiaoming Zhang, Xingxing Lu, Tengda Sun, Yue Qi, Yufan Lin, Xinling Yang, Li Zhang, Yun Ling. Design, Synthesis and Bioactivity of Sulfonyl Hydrazides and Hydrazides Containing Fragment 1,2,3,4-Tetrahydroisoquinoline [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 725-733.
[3]	Jianfei Gao, Shunyi Li, Yulong He, Yingxia Li, Heyao Wang, Erfang Huang, Chun Hu. Design, Synthesis and Biological Evaluation of FABP4/5 Inhibitors Based on Quinoline Scaffold [J]. Chinese Journal of Organic Chemistry, 2023, 43(2): 636-645.
[4]	Rong Zhang, Xiang Gao, Lingling Chen, Fajun Nan. Discovery and Structure-Activity Relationship Studies of Thiazole- Oxazole Tandem Heterocyclic RNA Splicing Inhibitors [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2925-2939.
[5]	Tianpeng Ge, Yanchen Yang, Chunpu Li, Jian Zhang, Hong Liu. Research Progress of Discoid Domain Receptor 1 (DDR1) Inhibitors [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2760-2773.
[6]	Guangping Liang, Wei Wang, Xuxiu Zhu, Guangyan Liang, Jun Yang, Daoping Wang. Synthesis and in Vitro Anti-tumor Activity of Novel Spliced Compounds of Zidovudine and 4-Anilinoquinazolines [J]. Chinese Journal of Organic Chemistry, 2022, 42(9): 2793-2805.
[7]	Chunxia Wang, Xiaodong Hu, Bin Xu, Chunyang Cao. Research Progress of Antiviral Drug Targeting the Main Protease of SARS-CoV-2 [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 1974-1999.
[8]	Junzhe Yang, Zichao Xu, Chunpu Li, Yuanzheng Cheng, Hong Liu. Research Progress of Tropomyosin Receptor Kinase (TRK) Inhibitors [J]. Chinese Journal of Organic Chemistry, 2022, 42(7): 2055-2069.
[9]	Changkai Wang, Tengda Sun, Xuebo Zhang, Xinling Yang, Xingxing Lu, Huan Xu, Fasheng Shi, Li Zhang, Yun Ling. Design, Synthesis and Bioactivity of Novel Fluoropyrazole Hydrazides [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1527-1536.
[10]	Can Yong, Yun Li, Tao Bi, Guofeng Chen, Dongxia Zheng, Zhouyu Wang, Yuanyuan Zhang. Research Progress on the Synthesis and Activity of D-Galactose Derived Small Galectin Inhibitors [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1307-1325.
[11]	Ming Cai, Liang Shao, Fan Yang, Jihong Zhang, Fei Yu. Design, Synthesis of Pentacyclic Triterpenoid Glucose Conjugate and in vitro Activity against Influenza Virus [J]. Chinese Journal of Organic Chemistry, 2022, 42(5): 1453-1462.
[12]	Fangxia Lin, Zhihong Wang, Decai Dai, Xueming Zhou, Luyong Wu. Two New Shikimic Acid Derivatives from the Flower of Trachycarpus fortunei [J]. Chinese Journal of Organic Chemistry, 2022, 42(4): 1248-1251.
[13]	Zirong Zeng, Mengmeng Zhang, Hong Wang, Jia Li, Yuewei Guo, Mingzhi Su. Chemical Constituents of Sinularia nanolobata from the South China Sea [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 891-895.
[14]	Yuanfang Kong, Bin Yang, Yan Zhuang, Jingyu Zhang, Demei Sun, Chunhong Dong. Research Progress on the Synthesis and Structure-Activity Relationship of Five Hypoglycemic Active Heterocycles Based on Dipeptidyl Peptidase 4 (DPP-4) Target Design [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 770-784.
[15]	Jing-Yu Yang, Min-Min Tang, Li Chen, Xin-Yi Lai, Xin Zhuo, Xue-Ming Zhou, Guang-Ying Chen. Study on the Secondary Metabolites of Endophytic Penicillium sclerotiorum HLL113 [J]. Chinese Journal of Organic Chemistry, 2022, 42(3): 896-900.

结构多样的HIV-1整合酶抑制剂:过去、现在和未来

Structurally Diverse HIV-1 Integrase Inhibitors: Past,Present and Perspective

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments