DNA/RNA polymerases

The inhibitory impact of tubercidin (7-Deazaadenosine) (0-10 nM; 14 d) on erythroid human myeloid progenitor cells and bone marrow is dose-dependent. On CFU-GM and BFU-E cells, tubercidin's half-life (IC50) is 3.4 nM and 3.7 nM, respectively.

In order to preserve the lethality of shell Tubercidin and enable a second iteration of the regimen, finally with 100%, Tubercidin (7-Deazaadenosine) (i.p. ; 5 mg/kg; 10 days) collaborates with NBMPR-P [3].

Cytotoxicity assay [2]
Cell Types: human bone marrow progenitor cells
Tested Concentrations: 0-10nM
Incubation Duration: 14 days
Experimental Results: Dose-dependent inhibitory effect on CFU-GM and BFU-E.

Animal/Disease Models: Female CD1 mice[2]
Doses: 5 mg/kg
Route of Administration: intraperitoneal (ip) injection; ]. 5 mg/kg; 10 day
Experimental Results: Protect mice from tuberculin.

6245 rat LD50 oral 16 mg/kg LUNGS, THORAX, OR RESPIRATION: PLEURAL EFFUSION; GASTROINTESTINAL: OTHER CHANGES; LUNGS, THORAX, OR RESPIRATION: PLEURAL EFFUSION Cancer Research., 29(116), 1969 [PMID:5763972]
6245 rat LD50 intraperitoneal 1 mg/kg LUNGS, THORAX, OR RESPIRATION: PLEURAL EFFUSION; GASTROINTESTINAL: PERITONITIS; LIVER: OTHER CHANGES Cancer Research., 29(116), 1969 [PMID:5763972]
6245 mouse LD50 oral 28320 ug/kg National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program., JAN1986
6245 mouse LD50 intraperitoneal 6 mg/kg Compounds Available for Fundamental Research, Volume II-6, Antibiotics, A Program of Upjohn Company Research Laboratory., 2(6)(-), 1971
6245 mouse LD50 intravenous 45 mg/kg Journal of Antibiotics, Series A., 10(201), 1957

[1]. On the mode of action of 7-deaza-adenosine (Tubercidin). Biochim Biophys Acta. 1967 Mar 29;138(1):10-25.

[2]. Antiviral activity of C-5 substituted tubercidin analogues. J Med Chem. 1984 Mar;27(3):285-92.

[3]. Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis. Antimicrob Agents Chemother. 1989 Jun;33(6):824-7.

Tubercidin is an N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus. It has a role as an antineoplastic agent, a bacterial metabolite and an antimetabolite. It is a N-glycosylpyrrolopyrimidine, a ribonucleoside and an antibiotic antifungal agent.
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.
Tubercidin has been reported in Plectonema radiosum, Actinopolyspora erythraea, and other organisms with data available.
Tubercidin is an antibiotic and adenosine analog isolated from the bacterium Streptomyces tubercidicus with potential antineoplastic activity. Tubercidin is incorporated into DNA and inhibits polymerases, thereby inhibiting DNA replication and RNA and protein synthesis. This agent also exhibits antifungal and antiviral activities. (NCI04)
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.

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The pyrrolo[2,3-d]pyrimidine nucleoside antibiotics tubercidin, toyocamycin, and sangivamycin and the synthetic analogues 5-chloro-, 5,6-dichloro-, 5-bromo-, 6-bromo-, 5,6-dibromo-, 5-iodo-, 5-(1-hydroxyethyl)-, 5-(1-methoxyethyl)-, (E)-5-(2-bromoethenyl)-, (E)-5-(2-cyanoethenyl)-, 5-(2-buten-1-yl)-, 5-(3-hydroxypropyl)-, and 5-butyltubercidin were evaluated for their antiviral properties against six RNA viruses and three DNA viruses in HeLa cell, primary rabbit kidney cell, and Vero cell cultures. Most of the derivatives had substantial activity against the RNA viruses, with the least activity shown by 6-bromo-, 5,6-dichloro-, and 5,6-dibromotubercidin. The C-5 substituted derivatives were quite toxic for the host cells. 5-(1-Hydroxyethyl)-, 5-(1-methoxyethyl)-, and 5-(2-buten-1-yl)tubercidin were more selective against reovirus type 1, parainfluenza virus type 3 and Coxsackie virus B4 than tubercidin and the 5-halotubercidins. When tested for in vivo activity against Coxsackie B4 virus infection in newborn NMRI mice, 5-(1-hydroxyethyl)- and 5-(1-methoxyethyl)tubercidin caused a significant decrease in the mortality rate at a dose level of 100 micrograms per mouse. The inhibitory effects on L-1210 cell growth were also determined, and toyocamycin (ID50 = 0.006 micrograms/mL) was found to be the most active compound. This study demonstrates the significance of structural modification at C-5 and the potential of C-5 substituted analogues of tubercidin as biologically active agents. [1]

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Host toxicity of the dose regimen of tubercidin (7-deazaadenosine) plus nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) used in combination therapy of schistosomiasis (M. H. el Kouni, D. Diop, and S. Cha, Proc. Natl. Acad. Sci. USA 80:6667-6670, 1983; M. H. el Kouni, N. J. Messier, and S. Cha, Biochem. Pharmacol. 36:3815-3821, 1987) was examined in vivo in mice and in vitro with human bone marrow progenitor cells. Four successive daily intraperitoneal injections of tubercidin at 5 mg/kg per day produced 100% mortality in mice within 3 to 5 days following the first injection, with massive peritonitis and intestinal obstruction secondary to abdominal adhesions. 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. 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. [2]

C11H14N4O4

266.25326

266.101

C, 49.62; H, 5.30; N, 21.04; O, 24.04

69-33-0

6245

White to off-white solid powder

1.9±0.1 g/cm3

648.8±55.0 °C at 760 mmHg

247-248 °C (decomp)

346.2±31.5 °C

0.0±2.0 mmHg at 25°C

1.834

-0.12

4

7

2

19

334

4

C1=CN(C2=NC=NC(=C21)N)[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O

HDZZVAMISRMYHH-KCGFPETGSA-N

InChI=1S/C11H14N4O4/c12-9-5-1-2-15(10(5)14-4-13-9)11-8(18)7(17)6(3-16)19-11/h1-2,4,6-8,11,16-18H,3H2,(H2,12,13,14)/t6-,7-,8-,11-/m1/s1

(2R,3R,4S,5R)-2-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol

7-Deazaadenosine; Antibiotic XK 101-1; B 120121; NSC 56408 SKI 26,996; tubercidin; 7-Deazaadenosine; 69-33-0; Sparsomycin A; Tubercidine; sparsamycin A; Antibiotic XK 101-1; SKI 26,996; Sparsomycin A; TBC; Tubercidin; Tubercidine; U 10071; U-10071; U10071

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 30 mg/mL (~112.68 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)