Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus

Kongkamnerd, Jarinrat; Cappelletti, Luca; Prandi, Adolfo; Seneci, Pierfausto; Rungrotmongkol, Thanyada; Jongaroonngamsang, Nutthapon; Rojsitthisak, Pornchai; Frecer, Vladimı́r; Milani, Adelaide; Cattoli, Giovanni; Terregino, Calogero; Capua, Ilaria; Beneduce, Luca; Gallotta, Andrea; Pengo, Paolo; Fassina, Giorgio; Miertus, Stanislav; De-Eknamkul, Wanchai

doi:10.1016/j.bmc.2012.01.026

Cited by 19 publications

(8 citation statements)

References 25 publications

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“…9-14 Zanamivir and oseltamivir (OS) are good leads to be optimized in the search for novel inhibitors. [15][16][17][18] Based on their structures, a few derivatives with selective NA inhibitory activities have been discovered, such as compounds 4 19 , 5 20 and 6. 21 Compounds 4 and 5, designed with the 150-cavity, are N1-selective inhibitors, but these compounds exhibit low inhibitory activities.…”

Section: Introductionmentioning

confidence: 99%

Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

Xie

Huang

et al. 2014

J. Med. Chem.

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To discover group-1-specific neuraminidase (NA) inhibitors that are especially involved in combating the H5N1 virus, two series of oseltamivir derivatives were designed and synthesized by targeting the 150-cavity. Among these, compound 20l was the most potent N1-selective inhibitor, with IC50 values of 0.0019, 0.0038, and 0.0067 μM against NAs from three H5N1 viruses. These values are better than those of oseltamivir carboxylate. Compound 32 was another potent N1-selective inhibitor that exhibited a 12-fold increase in activity against the H274Y mutant relative to oseltamivir carboxylate. Molecular docking studies revealed that the 150-cavity was an auxiliary binding site that may contribute to the high selectivity of these compounds. The present work is a significant breakthrough in the discovery of potent group-1-specific neuraminidase inhibitors, which may be further investigated for the treatment of infection by the H5N1 virus.

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Section: Introductionmentioning

confidence: 99%

Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

Xie

Huang

et al. 2014

J. Med. Chem.

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“…The spread and treatment of this disease is combated with vaccination and anti-influenza drugs. Several compounds targeting the virus neuraminidase have been synthesized, tested and approved for use in humans as anti-influenza agents [35][36][37] . Recently, a large group of angelicin derivatives was synthesized and tested as inhibitors of the influenza A/WSN/33 (H1N1) virus strain induced cytopathic effect 38 .…”

Section: Methods Model and Calculationsmentioning

confidence: 99%

Modeling the Relationships Between Molecular Structure and Inhibition of Virus-Induced Cytophatic Effects: Anti-Hiv-1 and Anti-H1n1 (Influenza A) Activities as Examples

Alarcón¹,

Gatica-Díaz²,

Gómez-Jeria³

2013

J. Chil. Chem. Soc.

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In this paper we tested the hypothesis that the building up of model-based methods to correlate molecular structure with the concentration required for the production of some biological effects such as giant cell formation, reduction of the number of viable cells, etc. is possible. We provide data supporting this model presenting structure-relationships results for two sets of molecules displaying inhibitory activity against some effects of HIV-1 and H1N1 viruses. The local atomic reactivity indices were calculated at the ZINDO/1 level of the theory. We found several statistically significant equations showing that some process is charge-, orbital-and/or steric-controlled. The main and most important conclusion is that the method, originally designed only for in vitro molecule-site equilibrium constants, nicely works for other properties like cytopathicity protection and cytostatic concentrations. This opens an entirely new research field and raises the possibility that this methodology be applied to other types of reports of biological activity data. We conjecture that this method is superior to the Hansch approach and that it is related in a still unknown form to the Hammett methodology.

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“…Recently continuous flow synthesis of ethyl shikimate, a key intermediate of industrial production route is also reported by Sagandira and Watts [136] in which esterification with ethanol using (COCl) 2 was carried out. Though there are also several reports [137][138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156] for the designed and synthesis of Tamiflu analogues as a safeguard against a mutation in influenza virus not described herein to make this article concise (Figure 5).…”

Section: Tamiflu Analoguesmentioning

confidence: 99%

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

2020

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Tamiflu (oseltamivir phosphate), clinically working antiviral chiral drug, is most effective against the infectious disease caused by both influenza A and B. It is also the last resort drug for the treatment of N1H1 virus infection at a high cost with minimal global availability. The current industrial method uses natural (‐)‐shikimic acid obtained from Chinese star anise and coffee beans, hence the limited natural resource and scarcity restricted the Tamiflu production. While most of the synthetic methods reported were composed of natural chiral pools and relatively low‐cost reagents, however, the industrial process is fundamentally limited to the use of hazardous azide or tedious purification methods. In case of an influenza outbreak, producing the Tamiflu according to its demand may be difficult. This document detailed the synthetic progress of chemistry over the last two decades emphasizing the starting materials, hazards of reagents, time needed, number of steps, and overall yields etc. for the interest in academia as well as industrial research.

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Synthesis and in vitro study of novel neuraminidase inhibitors against avian influenza virus

Cited by 19 publications

References 25 publications

Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

Discovery of N-Substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase

Modeling the Relationships Between Molecular Structure and Inhibition of Virus-Induced Cytophatic Effects: Anti-Hiv-1 and Anti-H1n1 (Influenza A) Activities as Examples

Synthetic Advancement of Neuraminidase Inhibitor “Tamiflu”

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