scholarly journals Isothiazolo[4,3-b]pyridines as inhibitors of cyclin G associated kinase: synthesis, structure–activity relationship studies and antiviral activity

MedChemComm ◽  
2015 ◽  
Vol 6 (9) ◽  
pp. 1666-1672 ◽  
Author(s):  
Jiahong Li ◽  
Sona Kovackova ◽  
Szuyuan Pu ◽  
Jef Rozenski ◽  
Steven De Jonghe ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Cyclin G

Starting from a known isothiazolo[4,3-b]pyridine scaffold, different series of novel, potent GAK ligands were synthesized.

scholarly journals Filovirus Antiviral Activity of Cationic Amphiphilic Drugs Is Associated with Lipophilicity and Ability To Induce Phospholipidosis

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Antonia P. Gunesch ◽  
Francisco J. Zapatero-Belinchón ◽  
Lukas Pinkert ◽  
Eike Steinmann ◽  
Michael P. Manns ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Chemical Properties ◽  
Structure Activity Relationship ◽  
Marburg Virus ◽  
Cell Entry ◽  
Activity Relationship ◽  
Common Mechanism ◽  
Structure Activity ◽  
Cationic Amphiphilic Drugs ◽  
Amphiphilic Drugs

ABSTRACT Several cationic amphiphilic drugs (CADs) have been found to inhibit cell entry of filoviruses and other enveloped viruses. Structurally unrelated CADs may have antiviral activity, yet the underlying common mechanism and structure-activity relationship are incompletely understood. We aimed to understand how widespread antiviral activity is among CADs and which structural and physico-chemical properties are linked to entry inhibition. We measured inhibition of Marburg virus pseudoparticle (MARVpp) cell entry by 45 heterogeneous and mostly FDA-approved CADs and cytotoxicity in EA.hy926 cells. We analyzed correlation of antiviral activity with four chemical properties: pKa, hydrophobicity (octanol/water partitioning coefficient; ClogP), molecular weight, and distance between the basic group and hydrophobic ring structures. Additionally, we quantified drug-induced phospholipidosis (DIPL) of a CAD subset by flow cytometry. Structurally similar compounds (derivatives) and those with similar chemical properties but unrelated structures (analogues) to those of strong inhibitors were obtained by two in silico similarity search approaches and tested for antiviral activity. Overall, 11 out of 45 (24%) CADs inhibited MARVpp by 40% or more. The strongest antiviral compounds were dronedarone, triparanol, and quinacrine. Structure-activity relationship studies revealed highly significant correlations between antiviral activity, hydrophobicity (ClogP > 4), and DIPL. Moreover, pKa and intramolecular distance between hydrophobic and hydrophilic moieties correlated with antiviral activity but to a lesser extent. We also showed that in contrast to analogues, derivatives had antiviral activity similar to that of the seed compound dronedarone. Overall, one-quarter of CADs inhibit MARVpp entry in vitro, and antiviral activity of CADs mostly relies on their hydrophobicity yet is promoted by the individual structure.

scholarly journals Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

PLoS ONE ◽  
2010 ◽  
Vol 5 (8) ◽  
pp. e12309 ◽  
Author(s):  
David Tyssen ◽  
Scott A. Henderson ◽  
Adam Johnson ◽  
Jasminka Sterjovski ◽  
Katie Moore ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Dual Action ◽  
Relationship Of
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