Tubercidin (Synonyms: 7-Deazaadenosine, 7-DZA, NSC 56408) |
| Catalog No.GC16879 |
Tubercidin is a pyrrolopyrimidine nucleoside analog with significant activity against schistosomal infections.
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Cas No.: 69-33-0
Sample solution is provided at 25 µL, 10mM.
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Tubercidin is a pyrrolopyrimidine nucleoside analog with significant activity against schistosomal infections. It has also been tested as a cancer chemotherapeutic agent, but its utility has been limited by nephrotoxicity[8]. As one of the most potent inhibitors of human liver SAH-hydrolase, Tubercidin enters cells via nucleoside transporters[7]. Upon intracellular metabolism of tubercidin to its mono, di, and tri-phosphate esters, it can substitute for adenosine nucleotides, and thereby interfere in the synthesis of DNA, RNA, and protein. As a toxic adenosine analog with antiviral, antitrypanosomal, and antifungal functions. Inhibits multiple metabolic processes which includes: RNA processing, nucleic acid synthesis, protein synthesis, and methylation of tRNA through intracellular incorporation into nucleic acids. Acts as a plant antifungal, inhibits mammalian SAHH (SAH hydrolase), and blocks purine biosynthesis in Candida famata[1].Tubercidin has been studied for antiviral and anticancer properties, is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties[4,5].
In vitro, tubercidin alone had a direct dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells, and consistent inhibition (50%) of granulocyte-macrophage CFU (CFU-GM) and erythroid burst-forming units (BFU-E) occurred at 2 to 3 nM tubercidin. At higher doses, BFU-E were more sensitive to tubercidin toxicity than CFU-GM. Complete inhibition (99%) of BFU-E colonies occurred at 10 nM tubercidin, while complete inhibition of CFU-GM occurred at 100 nM. NBMPR-P at 10 to 100 nM protected CFU-GM and BFU-E from tubercidin toxicity in a dose-dependent matter[3].Continuous exposure for 14 days to tubercidin alone is highly toxic to both human CFU-GM and BFU-E. The IC50s of tubercidin are 3.4±1.7 and 3.7±0.2 nM for CFU-GM and BFU-E, respectively. Tubercidin also has a direct dose-dependent inhibitory effect on myeloid and erythroid human bone marrow progenitor cells in vitro[6]. The inhibitor tubercidin proved to be highly antiviral against SARS-CoV-2, Tubercidin is a broad-spectrum MTase inhibitor active against both NSP16 and MTr1.tubercidin potently inhibited both NSP16 and MTr1 in vitro, further emphasizing that a concomitant inhibition of NSP16 and MTr1 is pivotal for effective antiviral treatment.[2,3]
Host toxicity of the dose regimen of tubercidin plus nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) used in combination therapy of schistosomiasis. Coadministration of NBMPR-P (25 mg/kg per day) protected the mice from the lethality of tubercidin and allowed the repetition of the regimen for a second time with 100% survival until the mice were sacrificed 22 days following the first injection. Blood chemistry, hematological studies, and histological examinations showed no evidence for injury to the liver, kidney, spleen, pancreas, mesentery, or peritoneal mesothelium.
References:
[1]: Stahmann KP, Revuelta JL,et,al. Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production. Appl Microbiol Biotechnol. 2000 May;53(5):509-16. doi: 10.1007/s002530051649. PMID: 10855708.
[2]:Bergant V, Yamada S, et,al. Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases. EMBO J. 2022 Jul 14:e111608. doi: 10.15252/embj.2022111608. Epub ahead of print. PMID: 35833542; PMCID: PMC9350232.
[3]:Schultz DC, Johnson RM, et,al. Pyrimidine inhibitors synergize with nucleoside analogues to block SARS-CoV-2. Nature. 2022 Apr;604(7904):134-140. doi: 10.1038/s41586-022-04482-x. Epub 2022 Feb 7. PMID: 35130559.
[4]:Olsen DB, Eldrup AB, et,al. A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties. Antimicrob Agents Chemother. 2004 Oct;48(10):3944-53. doi: 10.1128/AAC.48.10.3944-3953.2004. PMID: 15388457; PMCID: PMC521892.
[5]: Vittori S, Dal Ben D, et,al. Antiviral properties of deazaadenine nucleoside derivatives. Curr Med Chem. 2006;13(29):3529-52. doi: 10.2174/092986706779026228. PMID: 17168721.
[6]: el Kouni MH, Diop D, et,al. Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis. Antimicrob Agents Chemother. 1989 Jun;33(6):824-7. doi: 10.1128/AAC.33.6.824. PMID: 2764531; PMCID: PMC284239.
[7]: Fabianowska-Majewska K, Duley JA, et,al. Effects of novel anti-viral adenosine analogues on the activity of S-adenosylhomocysteine hydrolase from human liver. Biochem Pharmacol. 1994 Aug 30;48(5):897-903. doi: 10.1016/0006-2952(94)90360-3. PMID: 8093102.
[8]: Bisel HF, Ansfield FJ, et,al. Clinical studies with tubercidin administered by direct intravenous injection. Cancer Res. 1970 Jan;30(1):76-8. PMID: 4917978.
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