Terpene Derivatives: A Comprehensive Computational Insights in Drug-likeness and ADMT Properties, and DFT Study

Year 2024, Volume: 11 Issue: 2, 869 - 888, 15.05.2024

Goncagül Serdaroğlu

Abstract

In this study, the terpene-like compounds were investigated to explore the possible reactivity tendency using DFT/B3LYP/6-311G** level and evaluation of absorption, distribution, and metabolism characteristics. The lipophilicity indexes of terpenes revealed that the T1 and T2 molecules were more lipophilic than the other molecules, whereas the T5 and T6 molecules were less lipophilic. The water solubility scores obtained from ALI and ESOL approaches indicated that T5 and T6 functionalized with the -C=O group's most soluble compounds, while T2 was the least soluble among the compounds. Regarding absorption, the T5 molecule was determined to be a promising structure among the compounds. Also, all compounds' VD (L/kg) values were determined in the optimal range of 0.04-20 L/kg. The terpenes T1-T3 would exhibit a BBB Penetration at a medium level, while they would not be suitable structures for PPB %. The terpenes T4-T6 could be quite promising in distribution except for BBB Penetration. T6 structure was determined to be more suitable in terms of metabolism than the other terpenes. NBO analyses revealed that cieplak (σ→ σ*) interactions for T1-T4 would lower the stabilization energy, predicted at 7.04 kcal/mol. In contrast, the resonance (π→ π*) interaction for T5 was predicted with the energy of 20.26 kcal/mol, which was the highest contributed interaction to E(2). FMO analyses indicated that T5 (0.204 au) could prefer electron donation more than terpenes, while T4 (0.108 au) would prefer electron donation less. MEP plots implied that the surround of the oxygen atom for T3-T6 molecules would be the electron-rich region for the electrophiles, whereas the around of the double bonds of T1 and T2 would be possible sites for the electrophiles. According to the NPA approach, the atomic charge of the O1 atom of terpenes T4-T6 was predicted at -0.76279, -0.55670, and -0.55395, whereas the O28 atom' charge was found to be at -0.77131, remarkable. The findings from this study are anticipated to provide invaluable insights into the relationship between electronic structure, ADM properties, and toxicity. This could potentially guide the future discovery, development, and refinement of terpene-based therapeutics.

Keywords

Terpene, ADMT study, FMO, MEP

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