Relationship between chemical structure and growth-inhibitory activity of monoterpenoids against pneumonia causing...

Volatile monoterpenoids represent promising candidates for inhalation-based therapies of respiratory infections due to their volatility and antimicrobial properties. Using the broth microdilution volatilization method, this study assessed the in vitro growth-inhibitory effect of 31 monoterpenoids against common pneumonia-causing pathogens, including Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes, with the aim to determine the relationship between their chemical structure and antibacterial activity in vapor phase. Among all compounds tested, β-thujaplicin, carvacrol, thymol, and thymoquinone produced the strongest antibacterial effect. A comprehensive structure-activity relationship analysis of the chemical structure indicated that monoterpenoids bearing hydroxyl or ketone functional groups on six- or seven-membered ring structures, double bonds and hydrophobic groups exhibited enhanced antibacterial potency, in vapor phase. Furthermore, statistical analysis of molecular descriptors identified critical physicochemical characteristics which are linked to their antibacterial efficacy. Those include increased polar atom content, higher electronegativity, overall hydrophobicity, and π-electron distribution. The findings of this study add valuable insights into structural and molecular determinants of antimicrobial activity and provide theoretical background for development of inhalation therapies of respiratory infections based on volatile antimicrobial terpenoids.