Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus

Yu, Yongshi; Tazeem,; Xu, Zhichao; Du, Liaoqi; Jin, Mengyu; Dong, Chune; Zhou, Hai‐Bing; Wu, Shuwen

doi:10.1039/c8md00474a

Cited by 10 publications

(6 citation statements)

References 41 publications

(64 reference statements)

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“…Finally we chose to obtain compound 9 with a nitrobenzenesulfonamide moiety as a structural particular element of the dinucleoside. Indeed, as a global observation in medicinal chemistry the N-arylsulfonamide motif is regularly found in antitumor agents as in some antiviral inhibitors [19,20]. Further, we explored the combination of the nitro group with another substituent (MeO, CF 3 , Cl) at diverse positions in the phenyl ring resulting in the compounds 10e13 and we also removed the nitro group in 14 (Scheme 3).…”

Section: Rational Design Of Bisubstrate Compoundsmentioning

confidence: 99%

“…In the synthetic pathway of dinucleoside 1, the intermediate 19 bearing a 4-Ns-amide group was prepared. In view of the valuable properties of such motif in some antiviral or anticancer drugs [19,20] it seemed interesting to us to obtain dinucleoside 9 by simple acidic deprotection of 19. Of special interest, compound 9 showed a good and specific inhibition on SARS-CoV nsp14 confirming that the nosyl group contributes to the inhibitory activity with specificity.…”

Section: Rna Methyltransferase Activity Assaysmentioning

confidence: 99%

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Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase

Ahmed‐Belkacem

Sutto-Ortiz

Guiraud

et al. 2020

European Journal of Medicinal Chemistry

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The spreading of new viruses is known to provoke global human health threat. The current COVID-19 pandemic caused by the recently emerged coronavirus SARS-CoV-2 is one significant and unfortunate example of what the world will have to face in the future with emerging viruses in absence of appropriate treatment. The discovery of potent and specific antiviral inhibitors and/or vaccines to fight these massive outbreaks is an urgent research priority. Enzymes involved in the capping pathway of viruses and more specifically RNA N7-or 2 0 O-methyltransferases (MTases) are now admitted as potential targets for antiviral chemotherapy. We designed bisubstrate inhibitors by mimicking the transition state of the 2 0-O-methylation of the cap RNA in order to block viral 2 0-O MTases. This work resulted in the synthesis of 16 adenine dinucleosides with both adenosines connected by various nitrogen-containing linkers. Unexpectedly, all the bisubstrate compounds were barely active against 2 0-O MTases of several flaviviruses or SARS-CoV but surprisingly, seven of them showed efficient and specific inhibition against SARS-CoV N7-MTase (nsp14) in the micromolar to submicromolar range. The most active nsp14 inhibitor identified is as potent as but particularly more specific than the broad-spectrum MTase inhibitor, sinefungin. Molecular docking suggests that the inhibitor binds to a pocket formed by the S-adenosyl methionine (SAM) and cap RNA binding sites, conserved among SARS-CoV nsp14. These dinucleoside SAM analogs will serve as starting points for the development of next inhibitors for SARS-CoV-2 nsp14 N7-MTase.

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Section: Rational Design Of Bisubstrate Compoundsmentioning

confidence: 99%

Section: Rna Methyltransferase Activity Assaysmentioning

confidence: 99%

Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase

Ahmed‐Belkacem

Sutto-Ortiz

Guiraud

et al. 2020

European Journal of Medicinal Chemistry

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“…[17][18][19] Huge number of studies conducted the MDCK cell-line for the cell viability studies. [20][21][22][23][24][25][26][27][28] Alongside their availability, the non-cancerous MDCK cell-lines were chosen.…”

Section: Discussionmentioning

confidence: 99%

The Evaluation of Antiproliferative Effect of Imatinib Derivatives against Breast and Colon Cell-Lines

Abdul‐Rasheed¹,

Hussein²,

Mahdi³

et al. 2020

ijpqa

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Background: Cancer is considered as one of the major leading causes of death. Tyrosine kinase inhibitors are recognized for their potential antiproliferative effects. Materials and methods: In the previous study, the authors designed, synthesized, and characterized two imatinib derivatives. These derivatives were biologically evaluated with the utilization of MCF-7, HCT116, and MDCK cell lines. Results: In respect to the imatinib standard, compound 2b has superior activity against HCT116 cell line (IC50; 15.88 μg/mL against 18.52 μg/mL for imatinib) and an improved cytotoxic activity on MDCK cell line (IC50; 0.654 mg/mL against 0.272 mg/mL for imatinib). Conclusion: The two synthesized compounds showed biological activity against cancerous cell lines and improved cytotoxic activity against normal non-cancerous cell line with respect to the imatinib standard.

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“…[17][18][19][20][21][22][23][24][25][26][27][28] Imidazopyrimidines, imidazopyrazines, and imidazopyridines, which are imidazo-fused bicyclic heterocycles, are privileged pharmacophores in the field of organic and medicinal chemistry. These moieties can be used to treat cancer, [29] inflammation, [30] bacterial infection, [31] HIV, [32] cancer-induced osteoporosis, [33] Alzheimer's disease, [34] and diabetes. [35] Many commercially available drugs based on this moiety have been developed, including an anxiolytic drug (alpidem), [36] a hypnotic drug (zolpidem), [37] an anti-ulcer drug (zolimidine), [38] sedative agents (saripidem & necopidem), [39] and used in the treatment of HIV infection (GSK812397) [40] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Visible‐Light‐Promoted Synthesis of Fusesd Imidazoheterocycle by Eosin Y under Metal‐Free and Solvent‐Free Conditions

et al. 2021

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A mild, efficient, solvent free, metal free and operationally simple visible light promoted multicomponent reaction of styrene, 2-aminopyrimidine, and t-butyl isocyanide have been been gathered to provide a variety of fusesd fused imidazoheterocycle using Eosin Y as a photocatalyst. This approach delivers good to excellent yields of imidazoheterocycle using readily accessible and economical starting materials under ambient conditions. The reaction provides a broad substrate scope and is compatible with several functional groups.

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Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus

Abstract: A novel series of heteroaromatic-based benzenesulfonamide derivatives were identified as potent inhibitors of H5N1 influenza A virus.

Cited by 10 publications

References 41 publications

Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase

Synthesis of adenine dinucleosides SAM analogs as specific inhibitors of SARS-CoV nsp14 RNA cap guanine-N7-methyltransferase

The Evaluation of Antiproliferative Effect of Imatinib Derivatives against Breast and Colon Cell-Lines

Visible‐Light‐Promoted Synthesis of Fusesd Imidazoheterocycle by Eosin Y under Metal‐Free and Solvent‐Free Conditions

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