Abstract
Alternaramide is a cyclic pentadepsipeptide isolated from marine sources that has been shown to present weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus as well as inhibitory effects on inflammatory mediator expressions. Thus, this work reports the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide considering a CDFT-based computational peptidology (CDFT-CP) methodology that results from the combination of the chemical reactivity descriptors that arise from conceptual density functional theory (CDFT) together with some cheminformatics tools that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related to the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features. The results represent a new confirmation of the superiority of the MN12SX density functional in the fulfilment of the Janak and ionization energy theorems through the proposed KID procedure. This has been useful for the accurate prediction of the CDFT reactivity descriptors that help in understanding the chemical reactivity. The computational pharmacokinetics study revealed the potential ability of alternaramide as a therapeutic drug by interacting with GPCR ligands and protease inhibitors. The ADMET indices confirm this assertion through the absence of toxicity and good absorption and distribution properties.
Highlights
Another study demonstrated that the alternaramide cyclopentadepsipeptide displays inhibitory effects on inflammatory mediator expressions [10]
In light of these potential therapeutic properties, we present the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide using a CDFT-based computational peptidology (CDFT-CP) methodology [12,13,14,15,16,17,18,19,20], which is Journal of Chemistry based on the combination of chemical reactivity descriptors derived from conceptual density functional theory (CDFT) [21,22,23,24,25,26], together with some cheminformatics tools [27,28,29,30,31,32,33,34] that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related the ADMET features [35, 36]
Conceptual Density Functional eory (DFT) Calculations. e optimized molecular structure of alternaramide marine cyclopentadepsipeptide calculated according to the procedure presented in the Materials and Methods section is shown in Figure 2, while Figure 3 shows a schematic representation of the cyclopeptide showing an internal H-bond formed between O (5) and the H atom attached to N (9)
Summary
A CDFT-Based Computational Peptidology (CDFT-CP) Study of the Chemical Reactivity and Bioactivity of the Marine-Derived Alternaramide Cyclopentadepsipeptide. E first synthesis of alternaramide was presented by Horton and coworkers using solution phase coupling protocols and macrolactonization and macrolactamization routes while its structure was determined by single crystal X-ray analysis [11] In light of these potential therapeutic properties, we present the results of a computational study of the chemical reactivity and bioactivity properties of this cyclopentadepsipeptide using a CDFT-based computational peptidology (CDFT-CP) methodology [12,13,14,15,16,17,18,19,20], which is Journal of Chemistry based on the combination of chemical reactivity descriptors derived from conceptual density functional theory (CDFT) [21,22,23,24,25,26], together with some cheminformatics tools [27,28,29,30,31,32,33,34] that can be used to estimate the associated physicochemical parameters, to improve the process of virtual screening through a similarity search, and to identify the ability of the peptide to behave as a potential useful drug, complemented with an analysis of its bioactivity and pharmacokinetics indices related the ADMET (absorption, distribution, metabolism, excretion, and toxicity) features [35, 36]
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