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:: Volume 19, Issue 2 (7-2017) ::
J Gorgan Univ Med Sci 2017, 19(2): 77-83 Back to browse issues page
Effect of anti-HIV activity of novel compounds 8-phenyl-4-quinolone containing different substituents at position 3
N Golbabaei1 , R Zabihollahi2 , Z Hajimahdi3 , A Zarghi4 , MR Amiran5 , MR Aghasadeghi 6
1- M.Sc in Microbiology, Faculty of Biological Science, North-Tehran Branch, Islamic Azad University, Tehran, Iran
2- General Physician, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
3- Associate Professor, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Professor, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5- M.Sc in Biophysics, Laboratory Technician, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran
6- Professor, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran , mr_sadeqi@yahoo.com
Abstract:   (6509 Views)

Background and Objective: HIV treatment influences the global health and finding new compounds against HIV virus is increased. This study was done to evaluate anti-HIV activity of 8-phenyl-4-quinolone derivatives containing different substituents at position 3.

Methods: In this descriptive study, single cycle replicable (SCR) HIV Virions were produced by co-transfecting HEK 293T cells with pmzNL4-3, pSPAX.2, pMD2.G plasmids. HeLa cells were infected with the SCR virions and then inhibit of virus replication by compounds were measured by p24 Antigen with ELISA kit. The cytotoxicity of these compounds on HeLa cells were measured by XTT method.

Results: All compounds including NPZ_4F, NPZ-2F, NPZ-4CL and NPZ-2CL had the best inhibitory effect at a concentration of 100µM with the inhibition rate of respectively 51%, 48%, 33%, and 25%, respectively. The compounds of NPZ-4F and NPZ-2CL had negligible cellular toxicity and have inhibited HIV replication at the highest concentration. This issue can make them a valuable compound since they are better compounds in therapeutic terms, which at a suitable concentration, they have the lowest rate of cellular toxicity and highest power to inhibit HIV replication.

Conclusion: Novel compounds derived from 8-phenyl-4-quinolone containing different substituents at position 3 can prevent HIV replication which is capable of high anti-viral and low cellular toxicity and suitable candidates for further investigation in antiviral studies.

Keywords: Human immunodeficiency virus, Replication inhibitors, Cytotoxicity
Full-Text [PDF 300 kb] [English Abstract]   (12924 Downloads) |   |   Abstract (HTML)  (994 Views)  
Type of Study: Original Articles | Subject: Pharmacology
References
1. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May; 220(4599): 868-71.
2. Anglaret X. [Global AIDS epidemic: from epidemiology to universal treatment]. Rev Med Interne. 2008 Dec; 29 Suppl 3:S269-73. doi: 10.1016/j.revmed.2008.10.002 [Article in French]
3. Arora DR, Gautam V, Gill PS, Mishra N. Recent advances in antiretroviral therapy in HIV infection. J Indian Med Assoc. 2010 Jan; 108(1): 29-34.
4. Katzman M, Sudol M, Pufnock JS, Zeto S, Skinner LM. Mapping target site selection for the non-specific nuclease activities of retroviral integrase. Virus Res. 2000; 66(1): 87-100.
5. Cook PR. A model for reverse transcription by a dimeric enzyme. Journal of General Virology. 1993;74(4): 691-7. doi:10.1099/0022-1317-74-4-691
6. Sakuragi J, Iwamoto A, Shioda T. Dissociation of genome dimerization from packaging functions and virion maturation of human immunodeficiency virus type 1. J Virol. 2002; 76(3): 959-67. doi:10.1128/JVI.76.3.959-967.2002
7. Pauwels R, Balzarini J, Baba M, Snoeck R, Schols D, Herdewijn P, et al. Rapid and automated tetrazolium-based colorimetric assay for the detection of anti-HIV compounds. J Virol Methods. 1988 Aug; 20(4): 309-21.
8. Wang RR, Gu Q, Wang YH, Zhang XM, Yang LM, Zhou J, et al. Anti-HIV-1 activities of compounds isolated from the medicinal plant Rhus chinensis. J Ethnopharmacol. 2008 May; 117(2): 249-56. doi:10.1016/j.jep.2008.01.037
9. Madani N, Hubicki AM, Perdigoto AL, Springer M, Sodroski J. Inhibition of human immunodeficiency virus envelope glycoprotein- mediated single cell lysis by low-molecular-weight antagonists of viral entry. J Virol. 2007; 81(2): 532-8. doi:10.1128/JVI.01079-06
10. Zabihollahi R, Sadat SM, Vahabpour R, Aghasadeghi MR, Memarnejadian A, Ghazanfari T, et al. Development of single-cycle replicable human immunodeficiency virus 1 mutants. Acta Virol. 2011; 55(1): 15-22.
11. Sadat SM, Zabihollahi R, Vahabpour R, Azadmanesh K, Javadi F, Siadat SD, et al. Designing and biological evaluation of single cycle replicable HIV-1 system as a potential vaccine strategy. Clinical Microbiology and Infection. 2010 Nov; 16(2): S334.
12. Rezaei A, Zabihollahi R, Salehi M, Moghim SH, Tamizifar H, Yazdanpanahi N, et al. Designing a non-virulent HIV-1 strain:Potential implications for vaccine and experimental research. Journal of Research in Medical Sciences. 2007; 12(5): 227-34.
13. Campbell EM, Perez O, Melar M, Hope TJ. Labeling HIV-1 virions with two fluorescent proteins allows identification of virions that have productively entered the target cell. Virology. 2007; 360(2): 286-93. doi:10.1016/j.virol.2006.10.025
14. Cavrois M, Neidleman J, Yonemoto W, Fenard D, Greene WC. HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion. Virology. 2004 Oct; 328(1):36-44. doi:10.1016/j.virol.2004.07.015
15. Morgan JR, LeDoux JM, Snow RG, Tompkins RG, Yarmush ML. Retrovirus infection: effect of time and target cell number. J Virol. 1995 Nov; 69(11): 6994-7000.
16. Svarovskaia ES, Barr R, Zhang X, Pais GC, Marchand C, Pommier Y, et al. Azido-containing diketo acid derivatives inhibit human immunodeficiency virus type 1 integrase in vivo and influence the frequency of deletions at two-long-terminal-repeat-circle junctions. J Virol. 2004 Apr; 78(7): 3210-22.
17. Zhao Q, Ma L, Jiang S, Lu H, Liu S, He Y, et al. Identification of N-phenyl-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamides as a new class of HIV-1 entry inhibitors that prevent gp120 binding to CD4. Virology. 2005 Sep; 339(2): 213-25.
18. Ahmed N, Brahmbhatt KG, Sabde S, Mitra D, Singh IP, Bhutani KK. Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols. Bioorg Med Chem. 2010 Apr; 18(8): 2872-9. doi:10.1016/j.bmc.2010.03.015
19. Nagasawa JY, Song J, Chen H, Kim HW, Blazel J, Ouk S, et al. 6-Benzylamino 4-oxo-1,4-dihydro-1,8-naphthyridines and 4-oxo-1,4-dihydroquinolines as HIV integrase inhibitors. Bioorg Med Chem Lett. 2011 Jan; 21(2): 760-3. doi:10.1016/j.bmcl.2010.11.108
20. Asaadi Dalaei S, Zabihollahi R, Sadat S M, Siadat SD, Amirmozafari N, Farhang Esfahani A, et al. [Inhibitory Effects of Novel 3-Hydroxy-4-Pyridinones with Iron Chelating Activity against Production of HIV Virions]. J Mazandaran Univ Med Sci. 2013; 22(97): 179-87. [Article in Persian]
21. Sato M, Motomura T, Aramaki H, Matsuda T, Yamashita M, Ito Y, et al. Novel HIV-1 integrase inhibitors derived from quinolone antibiotics. J Med Chem. 2006 Mar; 49(5): 1506-8.
22. Hajimahdi Z, Zabihollahi R, Aghasadeghi M, Ashtiani SH, Zarghi A. Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities. Medicinal Chemistry Research. 2016; 25(9): 1861-77. doi:10.1007/s00044-016-1631-x
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Golbabaei N, Zabihollahi R, Hajimahdi Z, Zarghi A, Amiran M, Aghasadeghi M. Effect of anti-HIV activity of novel compounds 8-phenyl-4-quinolone containing different substituents at position 3. J Gorgan Univ Med Sci 2017; 19 (2) :77-83
URL: http://goums.ac.ir/journal/article-1-3081-en.html


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Volume 19, Issue 2 (7-2017) Back to browse issues page
مجله دانشگاه علوم پزشکی گرگان Journal of Gorgan University of Medical Sciences
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