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Tubercidin is systematically named (2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)oxolane-3,4-diol. It is an N-glycosylpyrrolopyrimidine ribonucleoside and a member of the 7-deazapurine class, characterized by the replacement of the nitrogen atom at position 7 of the purine ring with a carbon atom. This structural change allows tubercidin to mimic adenosine in biological systems. The 7-deaza modification makes it resistant to degradation by enzymes such as adenosine deaminase and adenosine phosphorylase, enabling it to persist longer inside cells. This stability enhances its ability to disrupt nucleic acid metabolism and other adenosine-dependent processes. This results in its potent biological activity and systemic toxicity. Other natural compounds like toyocamycin share this structural similarity, making 7-deazapurines an important class of bioactive nucleosides.{{Cite journal |last=Mulamoottil |first=Varughese A. |title=Tubercidin and Related Analogues: An Inspiration for 50 years in Drug Discovery |url=https://www.eurekaselect.com/article/69303 |journal=Current Organic Chemistry |language=en |volume=20 |issue=8 |pages=830–838 |doi=10.2174/1385272819666150803231652}}{{Cite web |title=tubercidin {{!}} SGD |url=https://www.yeastgenome.org/chemical/CHEBI:48267 |access-date=2025-06-09 |website=www.yeastgenome.org}}

Tubercidin is naturally produced by several species of actinomycetes, particularly within the genus Streptomyces. It was first discovered in Streptomyces tubercidicus, but later identified in multiple other strains. The following species have been reported to produce tubercidin:

• Actinopolyspora erythraea{{Cite journal |last=Zhao |first=Li-Xing |last2=Huang |first2=Sheng-Xiong |last3=Tang |first3=Shu-Kun |last4=Jiang |first4=Cheng-Lin |last5=Duan |first5=Yanwen |last6=Beutler |first6=John A. |last7=Henrich |first7=Curtis J. |last8=McMahon |first8=James B. |last9=Schmid |first9=Tobias |last10=Blees |first10=Johanna S. |last11=Colburn |first11=Nancy H. |last12=Rajski |first12=Scott R. |last13=Shen |first13=Ben |date=2011-09-23 |title=Actinopolysporins A–C and Tubercidin as a Pdcd4 Stabilizer from the Halophilic Actinomycete Actinopolyspora erythraea YIM 90600 |url=https://doi.org/10.1021/np200603g |journal=Journal of Natural Products |volume=74 |issue=9 |pages=1990–1995 |doi=10.1021/np200603g |issn=0163-3864 |pmc=3179765 |pmid=21870828}}
• Caulospongia biflabellata{{Cite journal |last=Biabani |first=Misbah F. |last2=Gunasekera |first2=Sarath P. |last3=Longley |first3=Ross E. |last4=Wright |first4=Amy E. |last5=Pomponi |first5=Shirley A. |date=2002-01-01 |title=Tubercidin, A Cytotoxic Agent from the Marine Sponge Caulospongia biflabellata |url=https://www.tandfonline.com/doi/full/10.1076/phbi.40.4.302.8469 |journal=Pharmaceutical Biology |language=en |volume=40 |issue=4 |pages=302–303 |doi=10.1076/phbi.40.4.302.8469 |issn=1388-0209}}
• Hassallia byssoidea{{Cite journal |last=Stewart |first=Jeffrey B. |last2=Bornemann |first2=Volker |last3=Chen |first3=JIAN Lu |last4=Moore |first4=Richard E. |last5=Caplan |first5=Faith R. |last6=Karuso |first6=Helen |last7=Larsen |first7=Linda K. |last8=Patterson |first8=Gregory M. L. |date=1988-08-25 |title=CYTOTOXIC, FUNGICIDAL NUCLEOSIDES FROM BLUE GREEN ALGAE BELONGING TO THE SCYTONEMATACEAE |url=https://www.jstage.jst.go.jp/article/antibiotics1968/41/8/41_8_1048/_article |journal=The Journal of Antibiotics |language=en |volume=41 |issue=8 |pages=1048–1056 |doi=10.7164/antibiotics.41.1048 |issn=0021-8820}}{{Cite journal |last=Barchi |first=Joseph J. |last2=Norton |first2=Ted R. |last3=Furusawa |first3=Eiichi |last4=Patterson |first4=Gregory M. L. |last5=Moore |first5=Richard E. |date=1983-01-01 |title=Identification of a cytotoxin from Tolypothrix byssoidea as tubercidin |url=https://www.sciencedirect.com/science/article/pii/S0031942200977124 |journal=Phytochemistry |volume=22 |issue=12 |pages=2851–2852 |doi=10.1016/S0031-9422(00)97712-4 |issn=0031-9422}}
• Lissoclinum timorense{{Cite journal |last=Mitchell |first=Scott S. |last2=Pomerantz |first2=Steven C. |last3=Concepción |first3=Gisela P. |last4=Ireland |first4=Chris M. |date=1996-01-01 |title=Tubercidin Analogs from the Ascidian Didemnum voeltzkowi |url=https://doi.org/10.1021/np960457f |journal=Journal of Natural Products |volume=59 |issue=10 |pages=1000–1001 |doi=10.1021/np960457f |issn=0163-3864}}
• Plectonema radiosum{{Cite journal |last=Mooberry |first=Susan L. |last2=Stratman |first2=Klemens |last3=Moore |first3=Richard E. |date=1995-09-25 |title=Tubercidin stabilizes microtubules against vinblastine-induced depolymerization, a taxol-like effect |url=https://www.sciencedirect.com/science/article/pii/030438359503940X |journal=Cancer Letters |volume=96 |issue=2 |pages=261–266 |doi=10.1016/0304-3835(95)03940-X |issn=0304-3835}}
• Pseudophormidium radiosum
• Scytonema saleyeriense
• Streptomyces sparsogenes{{Cite journal |last=Poehland |first=Benjamin L. |last2=Chan |first2=James A. |date=1988-01-01 |title=Direct broth assay for sparsomycin and related nucleoside antitumor antibiotics using reversed-phase high-performance liquid chromatography |url=https://www.sciencedirect.com/science/article/pii/S0021967301838619 |journal=Journal of Chromatography A |volume=439 |issue=2 |pages=459–465 |doi=10.1016/S0021-9673(01)83861-9 |issn=0021-9673}}
• Streptomyces tubercidicus{{Cite journal |last=Yoo |first=Jin-Cheol |last2=Han |first2=Ji-Man |last3=Ko |first3=Ok-Hyun |last4=Bang |first4=Hee-Jae |date=1998-12-01 |title=Purification and characterization of GTP cyclohydrolase I fromStreptomyces tubercidicus, a producer of tubercidin |url=https://doi.org/10.1007/BF02976759 |journal=Archives of Pharmacal Research |language=en |volume=21 |issue=6 |pages=692–697 |doi=10.1007/BF02976759 |issn=1976-3786}}{{Cite journal |last=Liu |first=Yan |last2=Gong |first2=Rong |last3=Liu |first3=Xiaoqin |last4=Zhang |first4=Peichao |last5=Zhang |first5=Qi |last6=Cai |first6=You-Sheng |last7=Deng |first7=Zixin |last8=Winkler |first8=Margit |last9=Wu |first9=Jianguo |last10=Chen |first10=Wenqing |date=2018-08-28 |title=Discovery and characterization of the tubercidin biosynthetic pathway from Streptomyces tubercidicus NBRC 13090 |url=https://doi.org/10.1186/s12934-018-0978-8 |journal=Microbial Cell Factories |volume=17 |issue=1 |pages=131 |doi=10.1186/s12934-018-0978-8 |issn=1475-2859 |pmc=6112128 |pmid=30153835}}
• Tolypothrix byssoidea
• Tolypothrix distorta

Due to its structural similarity to adenosine, tubercidin can interfere with various essential biological processes resultin in broad range of biological activities.

Tubercidin shows potent cytotoxic activity against various cancer cell lines, including P388 and A549 tumor cells, as well as human cancer cell lines such as HeLa, A375, and WM266.{{Cite journal |last=D'Errico |first=Stefano |last2=Falanga |first2=Andrea Patrizia |last3=Capasso |first3=Domenica |last4=Di Gaetano |first4=Sonia |last5=Marzano |first5=Maria |last6=Terracciano |first6=Monica |last7=Roviello |first7=Giovanni Nicola |last8=Piccialli |first8=Gennaro |last9=Oliviero |first9=Giorgia |last10=Borbone |first10=Nicola |date=2020-07-04 |title=Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7407906/ |journal=Pharmaceutics |volume=12 |issue=7 |pages=627 |doi=10.3390/pharmaceutics12070627 |issn=1999-4923 |pmc=7407906 |pmid=32635488}} It has shown promising anti-Small-Cell Lung Cancer (SCLC) activity both in vitro and in vivo. It selectively exhibits strong cytotoxicity against SCLC cell lines (DMS 53 and DMS 114) at low concentrations (CC50 of 0.19 µM and 0.14 µM, respectively), with minimal impact on normal bronchial cells. In SCLC xenograft mouse models, tubercidin treatment (5 mg/kg, three times a week) significantly inhibited tumor growth, with some instances of complete tumor regression.{{Cite journal |last=Chen |first=Jungang |last2=Barrett |first2=Lindsey |last3=Lin |first3=Zhen |last4=Kendrick |first4=Samantha |last5=Mu |first5=Shengyu |last6=Dai |first6=Lu |last7=Qin |first7=Zhiqiang |date=2022-05-01 |title=Identification of natural compounds tubercidin and lycorine HCl against small-cell lung cancer and BCAT1 as a therapeutic target |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9077304/ |journal=Journal of Cellular and Molecular Medicine |volume=26 |issue=9 |pages=2557–2565 |doi=10.1111/jcmm.17246 |issn=1582-4934 |pmc=9077304 |pmid=35318805}}The anticancer activity of tubercidin mainly arises due to the induction of apoptosis in these cells.{{Cite journal |last=Shen |first=Guowen |last2=Cheng |first2=Qingni |last3=Liang |first3=Lunmin |last4=Qin |first4=Yaping |last5=Cao |first5=Yunzhu |last6=Li |first6=Quanzhong |last7=Xiao |first7=Shengjun |date=2025-03-22 |title=Tubercidin enhances apoptosis in serum-starved and hypoxic mouse cardiomyocytes by inducing nuclear speckle condensation |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC11929321/ |journal=BMC cardiovascular disorders |volume=25 |issue=1 |pages=211 |doi=10.1186/s12872-025-04661-4 |issn=1471-2261 |pmc=11929321 |pmid=40121465}} 5-Iodotubercidin, a derivative of tubercidin, has been identified as a genotoxic agent and a potent activator of the tumor suppressor protein p53, triggering DNA damage, cell cycle arrest, and necroptosis in cancer models.{{Cite journal |last=Zheng |first=Biaolin |last2=Chen |first2=Xiubing |last3=Chen |first3=Fengping |last4=Liao |first4=Xiaomin |last5=Wang |first5=Feng |last6=Yang |first6=Zhe |last7=Yi |first7=Nan |last8=Shi |first8=Xiaoyan |last9=Qin |first9=Shanyu |last10=Jiang |first10=Haixing |date=2023 |title=5-Iodotubercidin Inhibits the Growth of Insulinoma Cells by Inducing Apoptosis |url=https://pubmed.ncbi.nlm.nih.gov/36758529 |journal=Neuroendocrinology |volume=113 |issue=6 |pages=641–656 |doi=10.1159/000529616 |issn=1423-0194 |pmid=36758529}}{{Cite journal |last=Zhang |first=Xin |last2=Jia |first2=Deyong |last3=Liu |first3=Huijuan |last4=Zhu |first4=Na |last5=Zhang |first5=Wei |last6=Feng |first6=Jun |last7=Yin |first7=Jun |last8=Hao |first8=Bin |last9=Cui |first9=Daxiang |last10=Deng |first10=Yuezhen |last11=Xie |first11=Dong |last12=He |first12=Lin |last13=Li |first13=Baojie |date=2013 |title=Identification of 5-Iodotubercidin as a genotoxic drug with anti-cancer potential |url=https://pubmed.ncbi.nlm.nih.gov/23667485 |journal=PloS One |volume=8 |issue=5 |pages=e62527 |doi=10.1371/journal.pone.0062527 |issn=1932-6203 |pmc=3646850 |pmid=23667485}} Current research aims in developing less toxic derivatives of tubercidin by C6, C7, or C8 modifications on the purine ring. Additionally, new platinum(II) complexes of tubercidin are being investigated for their enhanced selectivity toward tumor cells.

Tubercidin displays broad-spectrum antiviral activity against a range of viruses. It has shown efficacy against SARS-CoV-2, influenza B virus (IBV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV), and SADS-CoV.{{Cite journal |last=Wang |first=Tianliang |last2=Zheng |first2=Guanmin |last3=Chen |first3=Zilu |last4=Wang |first4=Yue |last5=Zhao |first5=Chenxu |last6=Li |first6=Yaqin |last7=Yuan |first7=Yixin |last8=Duan |first8=Hong |last9=Zhu |first9=Hongsen |last10=Yang |first10=Xia |last11=Li |first11=Wentao |last12=Du |first12=Wenjuan |last13=Li |first13=Yongtao |last14=Li |first14=Dongliang |date=2024-01-02 |title=Drug repurposing screens identify Tubercidin as a potent antiviral agent against porcine nidovirus infections |url=https://www.sciencedirect.com/science/article/pii/S016817022300237X |journal=Virus Research |volume=339 |pages=199275 |doi=10.1016/j.virusres.2023.199275 |issn=0168-1702 |pmc=10730850 |pmid=38008220}} It exhibits antiviral activity by interfering with multiple stages of the viral life cycle, including viral entry, replication, and release. It also suppresses the expression of viral non-structural protein 2 (nsp2) and activates innate immune responses through pathways such as RIG-I and NF-κB.{{Cite journal |last=Xu |first=Yuqian |last2=Zhu |first2=Zhenbang |last3=Zhang |first3=Meng |last4=Chen |first4=Lulu |last5=Tian |first5=Kegong |last6=Li |first6=Xiangdong |date=2024-03-05 |title=Tubercidin inhibits PRRSV replication via RIG-I/NF-κB pathways and interrupting viral nsp2 synthesis |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10913529/ |journal=Microbiology Spectrum |volume=12 |issue=3 |pages=e0347923 |doi=10.1128/spectrum.03479-23 |issn=2165-0497 |pmc=10913529 |pmid=38299833}} Tubercidin also acts as a bispecific inhibitor targeting both the viral NSP16 methyltransferase and the host enzyme MTr1, both of which are essential for efficient SARS-CoV-2 replication.{{Cite journal |last=Tsukamoto |first=Yuta |last2=Hiono |first2=Takahiro |last3=Yamada |first3=Shintaro |last4=Matsuno |first4=Keita |last5=Faist |first5=Aileen |last6=Claff |first6=Tobias |last7=Hou |first7=Jianyu |last8=Namasivayam |first8=Vigneshwaran |last9=vom Hemdt |first9=Anja |last10=Sugimoto |first10=Satoko |last11=Ng |first11=Jin Ying |last12=Christensen |first12=Maria H. |last13=Tesfamariam |first13=Yonas M. |last14=Wolter |first14=Steven |last15=Juranek |first15=Stefan |date=2023-02-10 |title=Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication |url=https://www.science.org/doi/10.1126/science.add0875 |journal=Science |volume=379 |issue=6632 |pages=586–591 |doi=10.1126/science.add0875}} Its derivatives have demonstrated significant immunomodulatory effects, helping to reduce the hyperinflammatory response associated with SARS-CoV infection.{{Cite journal |last=Bergant |first=Valter |last2=Yamada |first2=Shintaro |last3=Grass |first3=Vincent |last4=Tsukamoto |first4=Yuta |last5=Lavacca |first5=Teresa |last6=Krey |first6=Karsten |last7=Mühlhofer |first7=Maria-Teresa |last8=Wittmann |first8=Sabine |last9=Ensser |first9=Armin |last10=Herrmann |first10=Alexandra |last11=Vom Hemdt |first11=Anja |last12=Tomita |first12=Yuriko |last13=Matsuyama |first13=Shutoku |last14=Hirokawa |first14=Takatsugu |last15=Huang |first15=Yiqi |date=2022-09-01 |title=Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2'-O-ribose methyltransferases |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9350232/ |journal=The EMBO journal |volume=41 |issue=17 |pages=e111608 |doi=10.15252/embj.2022111608 |issn=1460-2075 |pmc=9350232 |pmid=35833542}} One derivative, 5-Hydroxymethyltubercidin (HMTU), has shown strong antiviral activity against several flaviviruses—such as dengue, Zika, and yellow fever as well as various coronaviruses. Its mechanism involves inhibiting the viral RNA-dependent RNA polymerase (RdRp), leading to premature termination of viral RNA synthesis.{{Cite journal |last=Uemura |first=Kentaro |last2=Nobori |first2=Haruaki |last3=Sato |first3=Akihiko |last4=Sanaki |first4=Takao |last5=Toba |first5=Shinsuke |last6=Sasaki |first6=Michihito |last7=Murai |first7=Akiho |last8=Saito-Tarashima |first8=Noriko |last9=Minakawa |first9=Noriaki |last10=Orba |first10=Yasuko |last11=Kariwa |first11=Hiroaki |last12=Hall |first12=William W. |last13=Sawa |first13=Hirofumi |last14=Matsuda |first14=Akira |last15=Maenaka |first15=Katsumi |date=2021-10-22 |title=5-Hydroxymethyltubercidin exhibits potent antiviral activity against flaviviruses and coronaviruses, including SARS-CoV-2 |url=https://pubmed.ncbi.nlm.nih.gov/34541466 |journal=iScience |volume=24 |issue=10 |pages=103120 |doi=10.1016/j.isci.2021.103120 |issn=2589-0042 |pmc=8433052 |pmid=34541466}}

Tubercidin displays potent antiparasitic activity against a range of protozoan parasites, including Trypanosoma brucei,{{Cite journal |last=Drew |first=Mark E. |last2=Morris |first2=James C. |last3=Wang |first3=Zefeng |last4=Wells |first4=Lance |last5=Sanchez |first5=Marco |last6=Landfear |first6=Scott M. |last7=Englund |first7=Paul T. |date=2003-11-21 |title=The Adenosine Analog Tubercidin Inhibits Glycolysis in Trypanosoma brucei as Revealed by an RNA Interference Library * |url=https://www.jbc.org/article/S0021-9258(20)75939-9/abstract |journal=Journal of Biological Chemistry |language=English |volume=278 |issue=47 |pages=46596–46600 |doi=10.1074/jbc.M309320200 |issn=0021-9258 |pmid=12972414}}{{Cite journal |last=Hulpia |first=Fabian |last2=Campagnaro |first2=Gustavo Daniel |last3=Scortichini |first3=Mirko |last4=Van Hecke |first4=Kristof |last5=Maes |first5=Louis |last6=de Koning |first6=Harry P. |last7=Caljon |first7=Guy |last8=Van Calenbergh |first8=Serge |date=2019-02-15 |title=Revisiting tubercidin against kinetoplastid parasites: Aromatic substitutions at position 7 improve activity and reduce toxicity |url=https://www.sciencedirect.com/science/article/pii/S0223523418310869 |journal=European Journal of Medicinal Chemistry |volume=164 |pages=689–705 |doi=10.1016/j.ejmech.2018.12.050 |issn=0223-5234}} Trypanosoma gambiense,{{Cite journal |last=Ogbunude |first=P. O. |last2=Ikediobi |first2=C. O. |date=1982-09-01 |title=Effect of nitrobenzylthioinosinate on the toxicity of tubercidin and ethidium against Trypanosoma gambiense |url=https://pubmed.ncbi.nlm.nih.gov/6128890 |journal=Acta Tropica |volume=39 |issue=3 |pages=219–224 |issn=0001-706X |pmid=6128890}} Trypanosoma congolense, Schistosoma mansoni, Schistosoma japonicum,{{Cite journal |last=el Kouni |first=Mahmoud H |date=2003-09-01 |title=Potential chemotherapeutic targets in the purine metabolism of parasites |url=https://www.sciencedirect.com/science/article/pii/S0163725803000718 |journal=Pharmacology & Therapeutics |volume=99 |issue=3 |pages=283–309 |doi=10.1016/S0163-7258(03)00071-8 |issn=0163-7258}} and various species of Leishmania.{{Cite journal |last=Aoki |first=J. I. |last2=Yamashiro-Kanashiro |first2=E. H. |last3=Ramos |first3=D. C. C. |last4=Cotrim |first4=P. C. |date=2009-01-01 |title=Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport |url=https://doi.org/10.1007/s00436-008-1177-z |journal=Parasitology Research |language=en |volume=104 |issue=2 |pages=223–228 |doi=10.1007/s00436-008-1177-z |issn=1432-1955}}{{Cite journal |last=Aoki |first=Juliana Ide |last2=Coelho |first2=Adriano Cappellazzo |last3=Muxel |first3=Sandra Marcia |last4=Zampieri |first4=Ricardo Andrade |last5=Sanchez |first5=Eduardo Milton Ramos |last6=Nerland |first6=Audun Helge |last7=Floeter-Winter |first7=Lucile Maria |last8=Cotrim |first8=Paulo Cesar |date=2016-09-08 |title=Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major |url=https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004972 |journal=PLOS Neglected Tropical Diseases |language=en |volume=10 |issue=9 |pages=e0004972 |doi=10.1371/journal.pntd.0004972 |issn=1935-2735 |pmc=5015992 |pmid=27606425}} A derivative, 3′-deoxytubercidin, has demonstrated strong antitrypanosomal activity. In mouse models, it successfully cured infections caused by Trypanosoma brucei evansi (Surra) and T. equiperdum (Dourine) when administered intraperitoneally, with no detectable toxicity at effective doses.{{Cite journal |last=Ilbeigi |first=Kayhan |last2=Mabille |first2=Dorien |last3=Roy |first3=Rajdeep |last4=Bundschuh |first4=Mirco |last5=Van de Velde |first5=Ewout |last6=Hulpia |first6=Fabian |last7=Van Calenbergh |first7=Serge |last8=Caljon |first8=Guy |date=2025-04-01 |title=3'-deoxytubercidin: A potent therapeutic candidate for the treatment of Surra and Dourine |url=https://pubmed.ncbi.nlm.nih.gov/39827514 |journal=International Journal for Parasitology. Drugs and Drug Resistance |volume=27 |pages=100580 |doi=10.1016/j.ijpddr.2025.100580 |issn=2211-3207 |pmc=11787584 |pmid=39827514}}{{Cite journal |last=Mabille |first=Dorien |last2=Ilbeigi |first2=Kayhan |last3=Hendrickx |first3=Sarah |last4=Ungogo |first4=Marzuq A. |last5=Hulpia |first5=Fabian |last6=Lin |first6=Cai |last7=Maes |first7=Louis |last8=de Koning |first8=Harry P. |last9=Van Calenbergh |first9=Serge |last10=Caljon |first10=Guy |date=2022-08-01 |title=Nucleoside analogues for the treatment of animal trypanosomiasis |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9111543/ |journal=International Journal for Parasitology. Drugs and Drug Resistance |volume=19 |pages=21–30 |doi=10.1016/j.ijpddr.2022.05.001 |issn=2211-3207 |pmc=9111543 |pmid=35567803}}

Tubercidin also exhibits antibiotic properties, showing activity against Mycobacterium tuberculosis and Streptococcus faecalis.{{Cite journal |last=Anzai |first=K. |last2=Nakamura |first2=G. |last3=Suzuki |first3=S. |date=1957-09-01 |title=A new antibiotic, tubercidin |url=https://pubmed.ncbi.nlm.nih.gov/13513512 |journal=The Journal of Antibiotics |volume=10 |issue=5 |pages=201–204 |issn=0021-8820 |pmid=13513512}} It, alongwith its derivative 5-iodotubercidin alsoshow notable antifungal effects, especially against Candida albicans, with its toxicity linked to uptake through the fungal concentrative nucleoside transporter (CNT).{{Cite journal |last=Ojima |first=Yoshihiro |last2=Yokota |first2=Naoki |last3=Tanibata |first3=Yuki |last4=Nerome |first4=Shinsuke |last5=Azuma |first5=Masayuki |date=2022-08-31 |title=Concentrative Nucleoside Transporter, CNT, Results in Selective Toxicity of Toyocamycin against Candida albicans |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC9431476/ |journal=Microbiology Spectrum |volume=10 |issue=4 |pages=e0113822 |doi=10.1128/spectrum.01138-22 |issn=2165-0497 |pmc=9431476 |pmid=35913167}}

Tubercidin's biological effects mainly arise from its structural similarity to adenosine which enables it to interfere with fundamental cellular processes. After cellular uptake via nucleoside transporters, tubercidin can be converted by adenosine kinase into its mono-, di-, and triphosphate forms. These active metabolites mimic natural adenosine nucleotides and compete with them, disrupting the fnuction of key enzymes like polymerases. As a result, tubercidin interferes with DNA replication, RNA transcription, and protein synthesis.{{Cite journal |last=Paterson |first=A R P |last2=Harley |first2=E R |last3=Cass |first3=C E |date=1984-12-15 |title=Inward fluxes of adenosine in erythrocytes and cultured cells measured by a quenched-flow method |url=https://doi.org/10.1042/bj2241001 |journal=Biochemical Journal |volume=224 |issue=3 |pages=1001–1008 |doi=10.1042/bj2241001 |issn=0264-6021 |pmc=1144539 |pmid=6525168}}{{Cite journal |last=Bloch |first=A. |last2=Mihich |first2=E. |last3=Leonard |first3=R. J. |last4=Nichol |first4=C. A. |date=1969-01-01 |title=Studies on the biologic activity and mode of action of 7-deazainosine |url=https://pubmed.ncbi.nlm.nih.gov/4974300 |journal=Cancer Research |volume=29 |issue=1 |pages=110–115 |issn=0008-5472 |pmid=4974300}}{{Cite journal |last=Lindberg |first=B. |last2=Klenow |first2=H. |last3=Hansen |first3=K. |date=1967-02-10 |title=Some properties of partially purified mammalian adenosine kinase |url=https://pubmed.ncbi.nlm.nih.gov/4290214 |journal=The Journal of Biological Chemistry |volume=242 |issue=3 |pages=350–356 |issn=0021-9258 |pmid=4290214}}

In addition to its broad effects on nucleic acid synthesis, tubercidin also targets specific enzymes and cellular pathways. One of its known targets is S-adenosylhomocysteine hydrolase (SAHH), an enzyme essential for maintaining proper methylation reactions by breaking down S-adenosylhomocysteine (SAH), a natural inhibitor of transmethylation. By inhibiting SAHH, tubercidin disrupts various methylation-dependent processes like cell signaling. It inhibits chemotaxis as well as chemotaxis-dependent cell streaming in organisms such as Dictyostelium and chemotaxis in neutrophils.{{Cite journal |last=Shu |first=Shi |last2=Mahadeo |first2=Dana C. |last3=Liu |first3=Xiong |last4=Liu |first4=Wenli |last5=Parent |first5=Carole A. |last6=Korn |first6=Edward D. |date=2006-12-26 |title=S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells, suggesting a role for transmethylation during migration |url=https://www.pnas.org/doi/full/10.1073/pnas.0609385103 |journal=Proceedings of the National Academy of Sciences |volume=103 |issue=52 |pages=19788–19793 |doi=10.1073/pnas.0609385103 |pmc=1750865 |pmid=17172447}}

In parasitic organisms such as in Trypanosoma brucei, tubercidin has been found to inhibit glycolysis by targeting the enzyme phosphoglycerate kinase. Since trypanosomes rely heavily on glycolysis for energy production, this makes glycolytic enzymes attractive targets for antitrypanosomal drugs.

Tubercidin has also been shown to disrupt the function of nuclear speckles (NSs), which are essential subnuclear structures enriched with RNA-binding proteins involved in mRNA splicing and processing. Upon treatment with tubercidin, poly(A)+ RNAs become dispersed and degraded across the nucleoplasm, while SC35-marked nuclear speckles remain condensed. This suggests that tubercidin selectively impairs mRNA processing without completely dismantling the speckles themselves. Under stress conditions such as hypoxia or serum starvation, this disruption can worsen cellular damage and promote apoptosis, particularly in sensitve cells like cardiomyocytes.{{Cite journal |last=Kurogi |first=Yutaro |last2=Matsuo |first2=Yota |last3=Mihara |first3=Yuki |last4=Yagi |first4=Hiroaki |last5=Shigaki-Miyamoto |first5=Kaya |last6=Toyota |first6=Syukichi |last7=Azuma |first7=Yuko |last8=Igarashi |first8=Masayuki |last9=Tani |first9=Tokio |date=2014-03-28 |title=Identification of a chemical inhibitor for nuclear speckle formation: Implications for the function of nuclear speckles in regulation of alternative pre-mRNA splicing |url=https://www.sciencedirect.com/science/article/pii/S0006291X14003222 |journal=Biochemical and Biophysical Research Communications |volume=446 |issue=1 |pages=119–124 |doi=10.1016/j.bbrc.2014.02.060 |issn=0006-291X}}

Despite potent biological activites, the clinical applications of tubercidin are significantly limited due to its toxicity to mammalian cells. This manifests itself mainly as hepatotoxicity, nephrotoxicity, and cardiotoxicity.{{Cite journal |last=Kolassa |first=Norbert |last2=Jakobs |first2=Ewa S. |last3=Buzzell‡ |first3=Gerald R. |last4=Paterson§ |first4=Alan R. P. |date=1982-05-15 |title=Manipulation of toxicity and tissue distribution of tubercidin in mice by nitrobenzylthioinosine 5'-monophosphate |url=https://www.sciencedirect.com/science/article/pii/0006295282904890 |journal=Biochemical Pharmacology |volume=31 |issue=10 |pages=1863–1874 |doi=10.1016/0006-2952(82)90489-0 |issn=0006-2952}}

Cardiotoxicity is a notable concern with tubercidin, particularly in individuals with existing heart conditions like ischemic cardiomyopathy. Tubercidin promotes apoptosis in heart muscle cells under stress, especially in hypoxic or starved conditions. This effect appears to be linked to tubercidin's interference with nuclear speckles which are important for processing mRNA and regulating gene activity. By disrupting these functions, tubercidin may worsen damage in already weakened heart tissue.

Hepatotoxicity and nephrotoxicity have been observed in vivo in mice and in vitro with human bone marrow progenitor cells. In mice, intravenous doses of 45 mg/kg caused high mortality rates, mainly due to liver damage. Kidney injury was also noted at higher doses. Co-administering nucleoside transport inhibitors like nitrobenzylthioinosine 5'-monophosphate (NBMPR-P) helped reduce liver toxicity by changing how tubercidin is distributed in the body. However, at high doses, NBMPR-P increased the risk of kidney damage.{{Cite journal |last=el Kouni |first=M. H. |last2=Diop |first2=D. |last3=O'Shea |first3=P. |last4=Carlisle |first4=R. |last5=Sommadossi |first5=J. P. |date=1989-06-01 |title=Prevention of tubercidin host toxicity by nitrobenzylthioinosine 5'-monophosphate for the treatment of schistosomiasis |url=https://pubmed.ncbi.nlm.nih.gov/2764531 |journal=Antimicrobial Agents and Chemotherapy |volume=33 |issue=6 |pages=824–827 |doi=10.1128/AAC.33.6.824 |issn=0066-4804 |pmc=284239 |pmid=2764531}}

Early Phase I clinical trials involving direct intravenous administration of tubercidin in humans found the drug to be unsuitable due to significant toxicity. Reported side effects included hepatic toxicity, renal toxicity like proteinuria and uremia, and hematological toxicity like venous thrombosis and leukopenia. These toxic effects have been a major barrier to the clinical use of tubercidin.{{Cite journal |last=Grage |first=T. B. |last2=Rochlin |first2=D. B. |last3=Weiss |first3=A. J. |last4=Wilson |first4=W. L. |date=1970-01-01 |title=Clinical studies with tubercidin administered after absorption into human erythrocytes |url=https://aacrjournals.org/cancerres/article-pdf/30/1/79/2386107/cr0300010079.pdf |journal=Cancer Research |volume=30 |issue=1 |pages=79–81 |issn=0008-5472 |pmid=4985935}}{{Cite journal |last=Grage |first=T. B. |last2=Rochlin |first2=D. B. |last3=Weiss |first3=A. J. |last4=Wilson |first4=W. L. |date=1970-01-01 |title=Clinical studies with tubercidin administered after absorption into human erythrocytes |url=https://pubmed.ncbi.nlm.nih.gov/4985935 |journal=Cancer Research |volume=30 |issue=1 |pages=79–81 |issn=0008-5472 |pmid=4985935}}{{Cite journal |last=Hochberg-Laufer |first=Hodaya |last2=Schwed-Gross |first2=Avital |last3=Neugebauer |first3=Karla M. |last4=Shav-Tal |first4=Yaron |date=2019-05-21 |title=Uncoupling of nucleo-cytoplasmic RNA export and localization during stress |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC6511838/ |journal=Nucleic Acids Research |volume=47 |issue=9 |pages=4778–4797 |doi=10.1093/nar/gkz168 |issn=1362-4962 |pmc=6511838 |pmid=30864659}}

The bioactivity of tubercidin alongwith its toxicity has spurred extemsive exploration into its derivatives particularly with modifications at C6, C7 and C8. Some of the key ones are:

• 5′-O-α-D-glucopyranosyl tubercidin: It is a disaccharide nucleoside isolated from blue-green algae. It exhibits antifungal activity.{{Cite journal |last=Stewart |first=Jeffrey B. |last2=Bornemann |first2=Volker |last3=Chen |first3=JIAN Lu |last4=Moore |first4=Richard E. |last5=Caplan |first5=Faith R. |last6=Karuso |first6=Helen |last7=Larsen |first7=Linda K. |last8=Patterson |first8=Gregory M. L. |date=1988-08-25 |title=CYTOTOXIC, FUNGICIDAL NUCLEOSIDES FROM BLUE GREEN ALGAE BELONGING TO THE SCYTONEMATACEAE |url=https://www.jstage.jst.go.jp/article/antibiotics1968/41/8/41_8_1048/_article |journal=The Journal of Antibiotics |language=en |volume=41 |issue=8 |pages=1048–1056 |doi=10.7164/antibiotics.41.1048 |issn=0021-8820}}{{Cite journal |last=Ouyang |first=Wenliang |last2=Huang |first2=Haiyang |last3=Yang |first3=Ruchun |last4=Ding |first4=Haixin |last5=Xiao |first5=Qiang |date=2020-07-29 |title=First Total Synthesis of 5'-O-α-d-Glucopyranosyl Tubercidin |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC7459636/ |journal=Marine Drugs |volume=18 |issue=8 |pages=398 |doi=10.3390/md18080398 |issn=1660-3397 |pmc=7459636 |pmid=32751067}}
• 5-Iodotubercidin: It is a genotoxic agent with anticancer properties. It activates tumor suppressor protein P53 leading to DNA damage and subsequently cell cycle arrest and cell death in cancer cells. It also has antifungal properties.{{Cite journal |last=Zhao |first=Jianyuan |last2=Liu |first2=Qian |last3=Yi |first3=Dongrong |last4=Li |first4=Quanjie |last5=Guo |first5=SaiSai |last6=Ma |first6=Ling |last7=Zhang |first7=Yongxin |last8=Dong |first8=Dongxin |last9=Guo |first9=Fei |last10=Liu |first10=Zhenlong |last11=Wei |first11=Tao |last12=Li |first12=Xiaoyu |last13=Cen |first13=Shan |date=2022-02-01 |title=5-Iodotubercidin inhibits SARS-CoV-2 RNA synthesis |url=https://pubmed.ncbi.nlm.nih.gov/35101534 |journal=Antiviral Research |volume=198 |pages=105254 |doi=10.1016/j.antiviral.2022.105254 |issn=1872-9096 |pmc=8800165 |pmid=35101534}}
• 5-hydroxymethyltubercidin (HMTU): It is a potent antiviral activity against a range og coronaviruses and flaviviruses, including SARS-CoV-2. It inhibits viral RNA-dependent RNA polymerase, thereby disrupting RNA synthesis by chain termination.
• 3'-deoxytubercidin: It is an antitrypanosomal agent.with no toxiciy at therapeutic doses.

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