Citation: Zai-Gang Luo, Yu Zhao, Chao Ma, Xue-Mei Xu, Xiao-Mei Zhang, Nian-Yu Huang, Hong-Qiu He. Synthesis and anti-integrase evaluation of novel calix[4]arene derivatives containing the triazolyl 1, 3-diketo moiety[J]. Chinese Chemical Letters, ;2014, 25(05): 737-740. doi: 10.1016/j.cclet.2014.03.012 shu

Synthesis and anti-integrase evaluation of novel calix[4]arene derivatives containing the triazolyl 1, 3-diketo moiety

1.
a College of Chemical Engineering, Anhui University of Science & Technology, Huainan 232001, China;
2.
b College of Chemistry and Life Sciences, China Three Gorges University, Yichang 443002, China;
3.
c Chongqing Center for Biomedicines and Medical Equipment, Chongqing Academy of Science and Technology, Chongqing 401123, China

Corresponding author: Zai-Gang Luo, Xue-Mei Xu,
Received Date: 13 December 2013
Available Online: 20 February 2014
Fund Project: The authors gratefully thank the National Natural Science Foundation of China (Nos.21102003, 21102084, 81202438) (Nos.21102003, 21102084, 81202438)

A series of novel calix[4]arene derivatives incorporating two triazolyl 1,3-diketo subunits in alternate positions at the lower rim were synthesized and screened for HIV integrase inhibition activity. The chemical structures of these compounds were confirmed by means of ¹H NMR, ¹³C NMR, and ESI-MS. Preliminary bioassays indicated that calix[4]arene derivatives proved to be more active than p-tert-butylcalix[4]arene derivatives. In particular, compound 4g presented the most potent integrase strand transfer inhibitory activity with an IC₅₀ value of 6.1 μmol/L.
- HIV-1 integrase inhibitor,
- Calix[4]arene derivative,
- 1,2,3-Triazole,
- 1,3-Diketo,
- Strand transfer
1. [1]
  [1] Y. Pommier, A.A. Johnson, C. Marchand, Integrase inhibitors to treat HIV/AIDS, Nat. Rev. Drug Discov. 4 (2005) 236-248.
2. [2]
  [2] (a) R. Dayam, N. Neamati, Small-molecule HIV-1 integrase inhibitors: the 2001- 2002 update, Curr. Pharm. Des. 9 (2003) 1789-1802; (b) R. Dayam, J.X. Deng, N. Neamati, HIV-1 integrase inhibitors: 2003-2004 update, Med. Res. Rev. 26 (2006) 271-309; (c) R. Dayam, R. Gundla, L.Q. Al-Mawsawi, N. Neamti, HIV-1 integrase inhibitors: 2005-2006 update, Med. Res. Rev. 28 (2008) 118-154.
3. [3]
  [3] Y. Goldgur, R. Craigie, G.H. Cohen, et al., Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: a platform for antiviral drug design, Proc. Natl. Acad. Sci. U.S.A. 96 (1996) 13040-13043.
4. [4]
  [4] M.L. Barreca, S. Ferro, A. Rao, et al., Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors, J. Med. Chem. 48 (2005) 7084-7088.
5. [5]
  [5] D.J. Hazuda, N.J. Anthony, R.P. Gomez, et al., A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase, Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 11233- 11238.
6. [6]
  [6] A. Bacchi, M. Biemmi,M. Carcelli, et al., From ligand to complexes. Part 2. Remarks on human immunodeficiency virus type 1 integrase inhibition by β-diketo acid metal complexes, J. Med. Chem. 51 (2008) 7253-7264.
7. [7]
  [7] Z.G. Luo, X.M. Xu, X.M. Zhang, L.M. Hu, Development of calixarenes, cyclodextrins and fullerenes as new platforms for anti-HIV drug design: an overview, Mini Rev. Med. Chem. 13 (2013) 1160-1165.
8. [8]
  [8] Â. de Fátima, S.A. Fernandes, A.A. Sabino, Calixarenes as newplatforms for drug design, Curr. Drug Discov. Technol. 6 (2009) 151-170.
9. [9]
  [9] V.R. Roman, I.B. Vyacheslav, I.K. Vitaly, Calixarenes in bio-medical researches, Curr. Med. Chem. 16 (2009) 1630-1655.
10. [10]
  [10] F. Perret, A.N. Lazar, A.W. Coleman, Biochemistry of the para-sulfonato-calix[- n]arenas, Chem. Commun. (2006) 2425-2438.
11. [11]
  [11] E. Da Silva, A.N. Lazar, A.W. Coleman, Biopharmaceutical applications of calixarenes, J. Drug Deliv. Sci. Technol. 14 (2004) 3-20.
12. [12]
  [12] A. Casnati, F. Sansone, R. Ungaro, Peptido- and glycocalixarenes: playing with hydrogen bonds around hydrophobic cavities, Acc. Chem. Res. 36 (2003) 246- 254.
13. [13]
  [13] M. Mourer, N. Psychogios, G. Laumond, A.M. Aubertin, J.B. Regnouf-de-Vains, Synthesis and anti-HIV evaluation of water-soluble calixarene-based bithiazolyl podands, Bioorg. Med. Chem. 18 (2010) 36-45.
14. [14]
  [14] L.K. Tsou, G.E. Dutschman, E.A. Gullen, et al., Discovery of a synthetic dual inhibitor of HIV and HCV infection based on a tetrabutoxy-calix[4]arene scaffold, Bioorg. Med. Chem. Lett. 20 (2010) 2137-2139.
15. [15]
  [15] V.R. Kamalraj, S. Senthil, P. Kannan, One-pot synthesis and the fluorescent behavior of 4-acetyl-5-methyl-1,2,3-triazole regioisomers, J. Mol. Struct. 892 (2008) 210-215.
16. [16]
  [16] M.J. Giffin, H. Heaslet, A. Brik, et al., A copper(I)-catalyzed 1,2,3-triazole azidealkyne click compound is a potent inhibitor of a multidrug-resistant HIV-1 protease variant, J. Med. Chem. 51 (2008) 6263-6270.
17. [17]
  [17] R. Alvarez, S. Velazquez, A. San-Felix, et al., 1,2,3-Triazole-[2',5'-bis-O-(tertbutyldimethylsilyl)- β-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogs: synthesis and anti-HIV-1 activity, J. Med. Chem. 37 (1994) 4185-4194.
18. [18]
  [18] Z.G. Luo, C.C. Zeng, L.F. Yang, et al., Synthesis of 6-sulfamoyl-4-oxoquinoline-3- carboxylic acid derivatives as integrase antagonists with anti-HIV activity, Chin. Chem. Lett. 20 (2009) 789-792.
19. [19]
  [19] L.M. Hu, S.L. Zhang, X.Z. He, et al., Design and synthesis of novel β-diketo derivatives as HIV-1 integrase inhibitors, Bioorg. Med. Chem. 20 (2012) 177-182.
20. [20]
  [20] L.M. Hu, S. Yang, Z.G. Luo, et al., Design, practical synthesis, and biological evaluation of novel 6-(pyrazolylmethyl)-4-quinoline-3-carboxylic acid derivatives as HIV-1 integrase inhibitors, Molecules 17 (2012) 10652-10666.
21. [21]
  [21] M. Yukito, H. Osamu, N. Yasuyuki, Enantioselective discrimination by cage-type cyclophanes bearing chiral binding sites in aqueous media, J. Am. Chem. Soc. 116 (1994) 2611-2612.
22. [22]
  [22] J. Guillon, J.M. Leger, P. Sonnet, C. Jarry, M. Robba, Synthesis of cone, partial-cone, and 1,3-alternate 25,27-bis[1-(2-ethyl)hexyl]- and 25,27-bis[1-(2-tert-butoxy) ethyl]calix[4]arene-crown-6 conformers as potential selective cesium extractants, J. Org. Chem. 65 (2000) 8283-8289.
23. [23]
  [23] Z.G. Luo, X.M. Xu, K. He, Synthesis of α,γ-diketo derivatives containing 1,2,3- triazole ring, Chem. Res. Appl. 25 (2013) 395-398.
24. [24]
  [24] V.S. Talanov, R.A. Bartsch, Highly selective preparation of conformationally rigidstereoisomeric calix[4]arenes with two carboxymethoxy groups, J. Chem. Soc., Perkin Trans. 1 (1999) 1957-1961.
25. [25]
  [25] C. Jaime, J. de Mendoza, P. Prados, P. Nieto, C. Sanchez, Carbon-13 NMR chemical shifts. A single rule to determine the conformation of calix[4]arenas, J. Org. Chem. 56 (1991) 3372-3376.
26. [26]
  [26] Q.H. Chu, L.X. Gao, D.M. Wang, Y.H. Qi, M.X. Ding, Spectroscopy of several β-diketone compounds and their tautomers, Chem. J. Chin. Univ. 21 (2000) 439- 443.
27. [27]
  [27] H.Q. He, X.H. Ma, B. Liu, W.Z. Chen, C.X. Wang, A novel high-throughput format assay for HIV-1 integrase strand transfer reaction using magnetic beads, Acta Pharmacol. Sin. 29 (2008) 397-404.
1. [1]
  Bairu Meng , Zongji Zhuo , Han Yu , Sining Tao , Zixuan Chen , Erik De Clercq , Christophe Pannecouque , Dongwei Kang , Peng Zhan , Xinyong Liu . Design, synthesis, and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs. Chinese Chemical Letters, 2024, 35(6): 108827-. doi: 10.1016/j.cclet.2023.108827
2. [2]
  Shiqi Xu , Zi Ye , Shuang Shang , Fengge Wang , Huan Zhang , Lianguo Chen , Hao Lin , Chen Chen , Fang Hua , Chong-Jing Zhang . Pairs of thiol-substituted 1,2,4-triazole-based isomeric covalent inhibitors with tunable reactivity and selectivity. Chinese Chemical Letters, 2024, 35(7): 109034-. doi: 10.1016/j.cclet.2023.109034
3. [3]
  Wujun Jian , Mong-Feng Chiou , Yajun Li , Hongli Bao , Song Yang . Cu-catalyzed regioselective diborylation of 1,3-enynes for the efficient synthesis of 1,4-diborylated allenes. Chinese Chemical Letters, 2024, 35(5): 108980-. doi: 10.1016/j.cclet.2023.108980
4. [4]
  Liangfeng Yang , Liang Zeng , Yanping Zhu , Qiuan Wang , Jinheng Li . Copper-catalyzed photoredox 1,4-amidocyanation of 1,3-enynes with N-amidopyridin-1-ium salts and TMSCN: Facile access to α-amido allenyl nitriles. Chinese Chemical Letters, 2024, 35(11): 109685-. doi: 10.1016/j.cclet.2024.109685
5. [5]
  Junjun Huang , Ran Chen , Yajian Huang , Hang Zhang , Anran Zheng , Qing Xiao , Dan Wu , Ruxia Duan , Zhi Zhou , Fei He , Wei Yi . Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α_1D/1A-adrenoceptor antagonist and homology modelling. Chinese Chemical Letters, 2024, 35(11): 109594-. doi: 10.1016/j.cclet.2024.109594
6. [6]
  Xiaohui Fu , Yanping Zhang , Juan Liao , Zhen-Hua Wang , Yong You , Jian-Qiang Zhao , Mingqiang Zhou , Wei-Cheng Yuan . Palladium-catalyzed enantioselective decarboxylation of vinyl cyclic carbamates: Generation of amide-based aza-1,3-dipoles and application to asymmetric 1,3-dipolar cycloaddition. Chinese Chemical Letters, 2024, 35(12): 109688-. doi: 10.1016/j.cclet.2024.109688
7. [7]
  Ze-Yuan Ma , Mei Xiao , Cheng-Kun Li , Adedamola Shoberu , Jian-Ping Zou . S-(1,3-Dioxoisoindolin-2-yl)O,O-diethyl phosphorothioate (SDDP): A practical electrophilic reagent for the phosphorothiolation of electron-rich compounds. Chinese Chemical Letters, 2024, 35(5): 109076-. doi: 10.1016/j.cclet.2023.109076
8. [8]
  An Lu , Yuhao Guo , Yi Yan , Lin Zhai , Xiangyu Wang , Weiran Cao , Zijie Li , Zhixia Zhao , Yujie Shi , Yuanjun Zhu , Xiaoyan Liu , Huining He , Zhiyu Wang , Jian-Cheng Wang . Nanomedicine integrating the lipidic derivative of 5-fluorouracil, miriplatin and PD-L1 siRNA for enhancing tumor therapy. Chinese Chemical Letters, 2024, 35(6): 108928-. doi: 10.1016/j.cclet.2023.108928
9. [9]
  Peiyan Zhu , Yanyan Yang , Hui Li , Jinhua Wang , Shiqing Li . Rh(Ⅲ)‐Catalyzed sequential ring‐retentive/‐opening [4 + 2] annulations of 2H‐imidazoles towards full‐color emissive imidazo[5,1‐a]isoquinolinium salts and AIE‐active non‐symmetric 1,1′‐biisoquinolines. Chinese Chemical Letters, 2024, 35(10): 109533-. doi: 10.1016/j.cclet.2024.109533
10. [10]
  Zhirong Yang , Shan Wang , Ming Jiang , Gengchen Li , Long Li , Fangzhi Peng , Zhihui Shao . One stone three birds: Ni-catalyzed asymmetric allenylic substitution of allenic ethers, hydroalkylation of 1,3-enynes and double alkylation of enynyl ethers. Chinese Chemical Letters, 2024, 35(8): 109518-. doi: 10.1016/j.cclet.2024.109518
11. [11]
  Yinwu Su , Xuanwen Zheng , Jianghui Du , Boda Li , Tao Wang , Zhiyan Huang . Green Synthesis of 1,3-Dibromoacetone Using Halogen Exchange Method: Recommending a Basic Organic Synthesis Teaching Experiment. University Chemistry, 2024, 39(5): 307-314. doi: 10.3866/PKU.DXHX202311092
12. [12]
  Zhuoming Liang , Ming Chen , Zhiwen Zheng , Kai Chen . Multidimensional Studies on Ketone-Enol Tautomerism of 1,3-Diketones By ¹H NMR. University Chemistry, 2024, 39(7): 361-367. doi: 10.3866/PKU.DXHX202311029
13. [13]
  Chunhua Ma , Mengjiao Liu , Siyu Ouyang , Zhenwei Cui , Jingjing Bi , Yuqin Jiang , Zhiguo Zhang . Metal-free construction of diverse 1,2,4-triazolo[1,5-a]pyridines on water. Chinese Chemical Letters, 2025, 36(1): 109755-. doi: 10.1016/j.cclet.2024.109755
14. [14]
  Gaofeng WANG , Shuwen SUN , Yanfei ZHAO , Lixin MENG , Bohui WEI . Structural diversity and luminescence properties of three zinc coordination polymers based on bis(4-(1H-imidazol-1-yl)phenyl)methanone. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 849-856. doi: 10.11862/CJIC.20230479
15. [15]
  Hai-Yang Song , Jun Jiang , Yu-Hang Song , Min-Hang Zhou , Chao Wu , Xiang Chen , Wei-Min He . Supporting-electrolyte-free electrochemical [2 + 2 + 1] annulation of benzo[d]isothiazole 1,1-dioxides, N-arylglycines and paraformaldehyde. Chinese Chemical Letters, 2024, 35(6): 109246-. doi: 10.1016/j.cclet.2023.109246
16. [16]
  Jinge Zhu , Ailing Tang , Leyi Tang , Peiqing Cong , Chao Li , Qing Guo , Zongtao Wang , Xiaoru Xu , Jiang Wu , Erjun Zhou . Chlorination of benzyl group on the terminal unit of A₂-A₁-D-A₁-A₂ type nonfullerene acceptor for high-voltage organic solar cells. Chinese Chemical Letters, 2025, 36(1): 110233-. doi: 10.1016/j.cclet.2024.110233
17. [17]
  Fan JIA , Wenbao XU , Fangbin LIU , Haihua ZHANG , Hongbing FU . Synthesis and electroluminescence properties of Mn²⁺ doped quasi-two-dimensional perovskites (PEA)₂Pb_yMn_1-yBr₄. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1114-1122. doi: 10.11862/CJIC.20230473
18. [18]
  Qingyun Hu , Wei Wang , Junyuan Lu , He Zhu , Qi Liu , Yang Ren , Hong Wang , Jian Hui . High-throughput screening of high energy density LiMn_1-xFe_xPO₄ via active learning. Chinese Chemical Letters, 2025, 36(2): 110344-. doi: 10.1016/j.cclet.2024.110344
19. [19]
  Keke Han , Wenjun Rao , Xiuli You , Haina Zhang , Xing Ye , Zhenhong Wei , Hu Cai . Two new high-temperature molecular ferroelectrics [1,5-3.2.2-Hdabcni]X (X = ClO₄⁻, ReO₄⁻). Chinese Chemical Letters, 2024, 35(6): 108809-. doi: 10.1016/j.cclet.2023.108809
20. [20]
  You Zhou , Li-Sheng Wang , Shuang-Gui Lei , Bo-Cheng Tang , Zhi-Cheng Yu , Xing Li , Yan-Dong Wu , Kai-Lu Zheng , An-Xin Wu . I₂-DMSO mediated tetra-functionalization of enaminones for the construction of novel furo[2′,3′:4,5]pyrimido[1,2-b]indazole skeletons via in situ capture of ketenimine cations. Chinese Chemical Letters, 2025, 36(1): 109799-. doi: 10.1016/j.cclet.2024.109799

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(667)
HTML views(21)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142