A series of nineteen amino acid analogues of amantadine (Amt) and rimantadine (Rim) were synthesized and their antiviral activity was evaluated against influenza virus A (H3N2). Among these analogues, the conjugation of rimantadine with glycine illustrated high antiviral activity combined with low cytotoxicity. Moreover, this compound presented a profoundly high stability after in vitro incubation in human plasma for 24 h. Its thermal stability was established using differential and gravimetric thermal analysis. The crystal structure of glycyl-rimantadine revealed that it crystallizes in the orthorhombic Pbca space group. The structure-activity relationship for this class of compounds was established, with CoMFA (Comparative Molecular Field Analysis) 3D-Quantitative Structure Activity Relationships (3D-QSAR) studies predicting the activities of synthetic molecules. In addition, molecular docking studies were conducted, revealing the structural requirements for the activity of the synthetic molecules.
- MeSH
- adamantan analogy a deriváty chemická syntéza chemie farmakologie MeSH
- antivirové látky chemická syntéza chemie farmakologie MeSH
- buněčná smrt účinky léků MeSH
- buňky MDCK MeSH
- diferenční termická analýza MeSH
- krystalografie rentgenová MeSH
- kvantitativní vztahy mezi strukturou a aktivitou * MeSH
- lidé MeSH
- metoda nejmenších čtverců MeSH
- molekulární konformace MeSH
- Orthomyxoviridae účinky léků MeSH
- počítačová simulace * MeSH
- proteinové domény MeSH
- proteiny virové matrix chemie MeSH
- psi MeSH
- rimantadin krev chemie MeSH
- simulace molekulového dockingu MeSH
- stabilita léku MeSH
- teplota MeSH
- vazebná místa MeSH
- vodíková vazba MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
