Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity

Standard

Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity. / Khramchikhin , Andrey V. ; Skryl’nikova, Mariya A. ; Esaulkova , Iana L. ; Sinegubova , Ekaterina O. ; Zarubaev , Vladimir V. ; Gureev, Maxim A. ; Puzyk, Aleksandra M. ; Ostrovskii , Vladimir A. .

In: Molecules (Basel, Switzerland), Vol. 27, No. 22, 7940, 16.11.2022.

Research output: Contribution to journal › Article › peer-review

Author

Khramchikhin , Andrey V. ; Skryl’nikova, Mariya A. ; Esaulkova , Iana L. ; Sinegubova , Ekaterina O. ; Zarubaev , Vladimir V. ; Gureev, Maxim A. ; Puzyk, Aleksandra M. ; Ostrovskii , Vladimir A. . / Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity. In: Molecules (Basel, Switzerland). 2022 ; Vol. 27, No. 22.

BibTeX

@article{826271a7f98b497097ef46950450668f,

title = "Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity",

abstract = "This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.",

keywords = "Drug Design, annelated heterocycles, influenza virus, anti-viral activity, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines, drug design, Triazoles/pharmacology, Antiviral Agents/pharmacology, Thiadiazines/pharmacology, Influenza A Virus, H1N1 Subtype, Ligands",

author = "Khramchikhin, {Andrey V.} and Skryl{\textquoteright}nikova, {Mariya A.} and Esaulkova, {Iana L.} and Sinegubova, {Ekaterina O.} and Zarubaev, {Vladimir V.} and Gureev, {Maxim A.} and Puzyk, {Aleksandra M.} and Ostrovskii, {Vladimir A.}",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

day = "16",

doi = "10.3390/molecules27227940",

language = "English",

volume = "27",

journal = "Molecules",

issn = "1420-3049",

publisher = "MDPI AG",

number = "22",

}

RIS

TY - JOUR

T1 - Novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine Derivatives: Synthesis, Anti-Viral In Vitro Study and Target Validation Activity

AU - Khramchikhin , Andrey V.

AU - Skryl’nikova, Mariya A.

AU - Esaulkova , Iana L.

AU - Sinegubova , Ekaterina O.

AU - Zarubaev , Vladimir V.

AU - Gureev, Maxim A.

AU - Puzyk, Aleksandra M.

AU - Ostrovskii , Vladimir A.

PY - 2022/11/16

Y1 - 2022/11/16

N2 - This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.

AB - This study of the interaction system of binucleophilic 3-substituted 4-amino-4H-1,2,4-triazole-5-thiols and 3-phenyl-2-propynal made it possible to develop a new approach to synthesis of such isomeric classes as 7-benzylidene-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine and 8-phenyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepine. Among the 20 compounds studied in vitro against influenza A/Puerto Rico/8/34 (H1N1) virus, half of them demonstrated selectivity index (SI) of 10 or higher and one of them (4-((3-phenylprop-2-yn-1-yl)amino)-4H-1,2,4-triazole-3-thiol) possessed the highest (SI > 300). Docking results and values showed that the preferred interactant for our ligands was M2 proton channel of the influenza A virus. Protein-ligand interactions modeling showed that the aliphatic moiety of ligands could negatively regulate target activity level.

KW - Drug Design

KW - annelated heterocycles

KW - influenza virus

KW - anti-viral activity

KW - [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

KW - [1,2,4]triazolo[3,4-b][1,3,4]thiadiazepines

KW - drug design

KW - Triazoles/pharmacology

KW - Antiviral Agents/pharmacology

KW - Thiadiazines/pharmacology

KW - Influenza A Virus, H1N1 Subtype

KW - Ligands

UR - https://www.mendeley.com/catalogue/50a2f62a-c314-3956-8989-f3c6c72dacd0/

UR - http://www.scopus.com/inward/record.url?scp=85142663787&partnerID=8YFLogxK

U2 - 10.3390/molecules27227940

DO - 10.3390/molecules27227940

M3 - Article

C2 - 36432042

VL - 27

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 22

M1 - 7940

ER -

ID: 100489051