tetano
Editor, Senior Moderator
Medchemcomm. 2018 Nov 23;10(1):89-100. doi: 10.1039/c8md00474a. eCollection 2019 Jan 1. [h=1]Design and synthesis of heteroaromatic-based benzenesulfonamide derivatives as potent inhibitors of H5N1 influenza A virus.[/h]
Yu Y[SUP]1,[/SUP][SUP]2[/SUP], Tazeem[SUP]2,[/SUP][SUP]3[/SUP], Xu Z[SUP]2[/SUP], Du L[SUP]1[/SUP], Jin M[SUP]2[/SUP], Dong C[SUP]2[/SUP], Zhou HB[SUP]2[/SUP], Wu S[SUP]1[/SUP].
[h=3]Author information[/h] 1 State Key Laboratory of Virology , College of Life Sciences , Wuhan University , Wuhan 430072 , China . Email: shuwenwu@hotmail.com. 2 Hubei Province Key Laboratory of Allergy and Immunology , Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals , Wuhan University School of Pharmaceutical Sciences , Wuhan 430071 , China . Email: zhouhb@whu.edu.cn. 3 Department of Chemistry , Shia P. G. College (University of Lucknow) , Lucknow , Uttar Pradesh 226020 , India.
[h=3]Abstract[/h] Influenza A virus is an enveloped negative single-stranded RNA virus that causes febrile respiratory infection and represents a clinically challenging threat to human health and even lives worldwide. Even more alarming is the emergence of highly pathogenic avian influenza (HPAI) strains such as H5N1, which possess much higher mortality rate (60%) than seasonal influenza strains in human infection. In this study, a novel series of heteroaromatic-based benzenesulfonamide derivatives were identified as M2 proton channel inhibitors. A systematic investigation of the structure-activity relationships and a molecular docking study demonstrated that the sulfonamide moiety and 2,5-dimethyl-substituted thiophene as the core structure played significant roles in the anti-influenza activity. Among the derivatives, compound 11k exhibited excellent antiviral activity against H5N1 virus with an EC[SUB]50[/SUB] value of 0.47 μM and selectivity index of 119.9, which are comparable to those of the reference drug amantadine.
PMID: 31559005 PMCID: PMC6735340 [Available on 2019-11-23] DOI: 10.1039/c8md00474a
Yu Y[SUP]1,[/SUP][SUP]2[/SUP], Tazeem[SUP]2,[/SUP][SUP]3[/SUP], Xu Z[SUP]2[/SUP], Du L[SUP]1[/SUP], Jin M[SUP]2[/SUP], Dong C[SUP]2[/SUP], Zhou HB[SUP]2[/SUP], Wu S[SUP]1[/SUP].
[h=3]Author information[/h] 1 State Key Laboratory of Virology , College of Life Sciences , Wuhan University , Wuhan 430072 , China . Email: shuwenwu@hotmail.com. 2 Hubei Province Key Laboratory of Allergy and Immunology , Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals , Wuhan University School of Pharmaceutical Sciences , Wuhan 430071 , China . Email: zhouhb@whu.edu.cn. 3 Department of Chemistry , Shia P. G. College (University of Lucknow) , Lucknow , Uttar Pradesh 226020 , India.
[h=3]Abstract[/h] Influenza A virus is an enveloped negative single-stranded RNA virus that causes febrile respiratory infection and represents a clinically challenging threat to human health and even lives worldwide. Even more alarming is the emergence of highly pathogenic avian influenza (HPAI) strains such as H5N1, which possess much higher mortality rate (60%) than seasonal influenza strains in human infection. In this study, a novel series of heteroaromatic-based benzenesulfonamide derivatives were identified as M2 proton channel inhibitors. A systematic investigation of the structure-activity relationships and a molecular docking study demonstrated that the sulfonamide moiety and 2,5-dimethyl-substituted thiophene as the core structure played significant roles in the anti-influenza activity. Among the derivatives, compound 11k exhibited excellent antiviral activity against H5N1 virus with an EC[SUB]50[/SUB] value of 0.47 μM and selectivity index of 119.9, which are comparable to those of the reference drug amantadine.
PMID: 31559005 PMCID: PMC6735340 [Available on 2019-11-23] DOI: 10.1039/c8md00474a