A nucleoside reverse transcriptase inhibitor
Zidovudine is an inhibitor of the reverse transcriptase of HIV-1[1].
Zidovudine is the first effective agent for the management of HIV-1 infection and is approved by FDA as a drug for AIDs in 1987. As a nucleoside analogue, zidovudine inhibits the activity of the reverse transcriptase with its triphosphate structure. In the in vitro studies, zidovudine shows strong inhibition of HIV-1 replication and the cytopathic effect of the virus. The addition of 5μM and 10μM zidovudine completely protects TM3 cells (a normal IL-2-dependent helper/inducer T-cell clone) and ATH8 cells against the cytopathic effect of HIV. It exhibits complete inhibition of reverse transcriptase at concentration up to 0.5μM. However, the resistance of zidovudine has been found in vitro and in vivo since 1989 [1, 2].
参考文献:
[1] Mitsuya H, Weinhold K J, Furman P A, et al. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proceedings of the National Academy of Sciences, 1985, 82(20): 7096-7100.
[2] McLeod G X, Hammer S M. Zidovudine: five years later. Annals of internal medicine, 1992, 117(6): 487-501.
| Cell experiment [1]: | |
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Cell lines |
SP and 63 cells |
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Preparation method |
The solubility of this compound in DMSO is > 8.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0 ~ 1 mM; 1 hr |
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Applications |
In the pretreated and recently infected SP and 63 cells, Zidovudine exhibited anti-HIV-1 activity, with an ED50 value of 0.001 mM. Moreover, additive effect was observed when Zidovudine was combined with Hydroxychloroquine. Viral replication was reduced to background reverse transcriptase levels. However, Zidovudine did not showed anti-HIV-1 activity towards chronically infected 63HIV and SPH cells. |
| Animal experiment [2]: | |
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Animal models |
Mice |
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Dosage form |
100 mg/kg; p.o.; a single dose |
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Applications |
In mice, the plasma concentration of Zidovudine increased rapidly after administration, reaching 41.69 μg/mL at the 0.75th hr, and followed by a decrease to ~4.64 and 0.45 μg/mL at the 4th and 8th hrs, respectively. The AUC level of Zidovudine was 85.23 ± 5.23 mg*h/mL. The Cmax and tmax values for Zidovudine were 41.69 ± 2.61 μg/mL and 0.75 ± 0.00 hr, respetively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Chiang G, Sassaroli M, Louie M, Chen H, Stecher VJ, Sperber K. Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther. 1996 Nov-Dec;18(6):1080-92. [2]. Li W, Chang Y, Zhan P, Zhang N, Liu X, Pannecouque C, De Clercq E. Synthesis, in vitro and in vivo release kinetics, and anti-HIV activity of a sustained-release prodrug (mPEG-AZT) of 3'-azido-3'-deoxythymidine (AZT, Zidovudine). ChemMedChem. 2010 Nov 8;5(11):1893-8. | |
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