Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Wu, Runzhi; Smidansky, Eric D.; Oh, Hyung Suk; Takhampunya, Ratree; Padmanabhan, Radhakrishnan; Cameron, Craig Ε.; Peterson, Blake R.

doi:10.1021/jm100593s

Cited by 52 publications

(50 citation statements)

References 40 publications

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“…The observed activity range is comparable with the findings of Xianchao G. Zhang. A correlation of our findings with the experimental observations of Wu et al [] and Muller et al [] suggests that the putative target for Bz‐Trp‐TSC could be the virus RNA synthesis [Zhang et al, ] (Fig. ).…”

Section: Resultssupporting

confidence: 88%

Antiviral activity of Thiosemicarbazones derived from α‐amino acids against Dengue virus

Padmanabhan

Sheriff

Kaveri

et al. 2016

Journal of Medical Virology

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The endemicity and seasonal outbreaks of Dengue disease in most tropical and subtropical countries underscores an urgent need to develop effective prevention and control measures. Development of a Dengue vaccine, which is complicated by the Antibody Dependent Enhancement effect (ADE), a viral inhibitor, seems prudent as it would inhibit the spread of the virus. In vitro methods such as MTT assay and plaque formation unit reduction assays were employed for screening the viral inhibitory property of α-amino acid based Thiosemicarbazides. The results elicits that at concentrations not exceeding the maximum non cytotoxic concentration (MNCC), these compounds completely prevented Dengue virus infection in vero cells as indicated by the absence of cytopathic effects in a dose-dependent manner. The high potency of Bz-Trp-TSC against all four types of Dengue virus infection elevates Thiosemicarbazide as a lead antiviral agent for Dengue disease. Screening small molecules for antiviral activity against the most rapidly spreading mosquito-borne viral disease is being explored by several research groups. Our findings would help to augment the efforts to identify the lead compounds for antiviral therapy to combat the Dengue disease. J. Med. Virol. 89:546-552, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Resultssupporting

confidence: 88%

Antiviral activity of Thiosemicarbazones derived from α‐amino acids against Dengue virus

Padmanabhan

Sheriff

Kaveri

et al. 2016

Journal of Medical Virology

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“…As far as we are aware, this substance is the most potent inhibitor uncovered to date using a cell-based DENV replicon assay. 5,6,[8][9][10][11][12][13][15][16][17]19,20,26,31,32 ■ CHEMISTRY…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives as a New Class of Potent Dengue Virus Inhibitors

et al. 2012

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The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antidengue activity relationship studies. Among the series of 2,4-diaminoquinazoline derivative probed, 4o was observed to display both the highest antiviral potency (EC(50) = 2.8 nM, SI > 1000) and an excellent pharmacokinetic profile.

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“…Data from Section is summarized in Table . 6‐Methyl‐7‐deazapurine ribonucleoside ( 35a ) showed potent anti‐dengue activity both in a replicon assay (EC 50 = 0.877 μM) and in an infectivity assay . Unfortunately, cytotoxicities against host cells were not reported in this study, however, 6‐methyl‐7‐deazapurine ribonucleoside ( 35a ) was shown to be highly cytotoxic towards human fibroblasts and therefore anti‐dengue activity caused by unspecific cytotoxicity of the compound 35a cannot be ruled out.…”

Section: Nucleosides With Antiviral Activitiesmentioning

confidence: 79%

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

Perlíková

Hocek

2017

Medicinal Research Reviews

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Abstract7‐Deazapurine (pyrrolo[2,3‐d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five‐membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base‐pairing in DNA or RNA or better binding to enzymes. Several types of 7‐deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7‐hetaryl‐7‐deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6‐hetaryl‐7‐deazapurine and thieno‐fused deazapurine ribonucleosides, is not yet known. Many 7‐deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar‐modified derivatives of 7‐deazapurine nucleosides are also strong antivirals. Most important are 2′‐C‐methylribo‐ or 2′‐C‐methyl‐2′‐fluororibonucleosides with anti‐HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.

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Synthesis of a 6-Methyl-7-deaza Analogue of Adenosine That Potently Inhibits Replication of Polio and Dengue Viruses

Cited by 52 publications

References 40 publications

Antiviral activity of Thiosemicarbazones derived from α‐amino acids against Dengue virus

Antiviral activity of Thiosemicarbazones derived from α‐amino acids against Dengue virus

Discovery and Optimization of 2,4-Diaminoquinazoline Derivatives as a New Class of Potent Dengue Virus Inhibitors

Pyrrolo[2,3‐d]pyrimidine (7‐deazapurine) as a privileged scaffold in design of antitumor and antiviral nucleosides

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