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.

• Klíčová slova
• 3D-QSAR, LC–MS/MS., X-Ray crystallography, adamantane derivatives, amino acids, mass spectrometry, molecular docking, plasma stability,
• 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
• Názvy látek
• adamantan MeSH
• antivirové látky MeSH
• M2 protein, Influenza A virus MeSH Prohlížeč
• proteiny virové matrix MeSH
• rimantadin MeSH