Abstract
Betulinic and melaleucic acids, lupan-skeleton triterpenes with very similar structure, present marked differences in anti-malarial activity. While betulinic acid and some of its analogs exhibit strong activity, melaleucic acid is inactive. In the present work, a theoretical approach was used to explain such differences, using Austin Model 1 (AM1) and density functional theory (DFT)/Becke, three-parameter, Lee-Yang-Parr (B3LYP) approaches, and AutoDock Vina calculations. The initial results showed no significant differences between structural and electronic properties. On the other hand, studies of the geometry of molecular clusters with both compounds revealed significant differences. Melaleucic acid clusters were shown to be stable enough to influence the substrate-protein interaction, unlike betulinic acid, which was unable to form clusters comparable to melaleucic acid ones. The present study suggests the molecular clusters as a new factor that has a great influence on the mechanism of biomolecular activity.
Highlights
The activities of organic compounds are closely associated with the characteristics of the individual molecules, such as geometry, functional groups and structural rigidity
We analyze the isolated molecules of betulinic acid (BetAc) and melaleucic acid (MelAc) while searching for differences that could justify the great difference between their activities
The total single point energy (ET) indicates that BetAc is in a higher level of energy than MelAc, which suggests that, at C14 position, COOH leads to lower energies than CHCl3 and (CH3) (Table S2, SI section)
Summary
The activities of organic compounds are closely associated with the characteristics of the individual molecules, such as geometry, functional groups and structural rigidity. Since BetAc and MelAc are close analogs, the difference in activities may be due to two causes: (i) a fundamental difference in some structural or electronic properties between the triterpenes; and (ii) an extramolecular factor, during the interaction and organization between several molecules, while forming stable molecular agglomerates (clusters).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
