Abstract
As a continuation of our research on the chemical reactivity, pharmacokinetics and ADMET properties of cyclopeptides of marine origin with potential therapeutic abilities, in this work our already presented integrated molecular modeling protocol has been used for the study of the chemical reactivity and bioactivity properties of the Veraguamides A–G family of marine natural drugs. This protocol results from the estimation of the conceptual density functional theory (CDFT) chemical reactivity descriptors together with several chemoinformatics tools commonly considered within the process of development of new therapeutic drugs. CP-CDFT is a branch of computational chemistry and molecular modeling dedicated to the study of peptides, and it is a protocol that allows the estimation with great accuracy of the CDFT-based reactivity descriptors and the associated physical and chemical properties, which can aid in determining the ability of the studied peptides to behave as potential useful drugs. Moreover, the superiority of the MN12SX density functional over other long-range corrected density functionals for the prediction of chemical and physical properties in the presence of water as the solvent is clearly demonstrated. The research was supplemented with an investigation of the bioactivity of the molecular systems and their ADMET (absorption, distribution, metabolism, excretion, and toxicity) parameters, as is customary in medicinal chemistry. Some instances of the CDFT-based chemical reactivity descriptors’ capacity to predict the pKas of peptides as well as their potential as AGE inhibitors are also shown.
Highlights
Understanding the ability of the natural world to produce secondary metabolites is crucial in a number of fields, including medication development
The objective of this work is to report the results of a computational study of the bioactivity properties and chemical reactivity of the members of this family of cyclic peptides on the basis of the CDFT-based computational peptidology (CDFT-CP) methodology [15,16,17,18,19] founded on the combination of the chemical reactivity descriptors from conceptual density functional theory (CDFT) [25,26,27,28,29,30] with some cheminformatics tools [31,32,33,34,35,36,37,38] which may be utilized to assess the associated physicochemical properties to enhance the virtual screening procedure and to detect the ability of the molecules to act as a possible useful drugs, complemented with an analysis of its bioactivity and pharmacokinetics characteristics linked to the ADMET features [39,40,41]
It is evident that within the Generalized Kohn-Sham (GKS) version of Density Functional Theory (DFT), some relationships exist between the KID methodology and the ionization energy theorem, which is a corollary of the Janak theorem [20,21,22,23,24]
Summary
Understanding the ability of the natural world to produce secondary metabolites is crucial in a number of fields, including medication development. The marine environment is the largest terrestrial ecosystem and prolific producer of biologically active compounds, accounting for more than 70% of the Earth’s surface due to its tremendous richness, which is mostly unexplored compared to terrestrial habitats. Marine habitats contain a large number of unique bioactive compounds with significant therapeutic promise. To cope with abnormal environmental conditions such as oxidative stress, photodynamic damage, and high temperatures, marine animals have been known to produce bioactive chemicals. The variety of bioactive marine compounds with great therapeutic potential is unrivaled, and the chemical and physical conditions of the sea play a role in their development. Many academics are investigating marine natural chemicals with a wide variety of biological activity as a possible source for developing human health-care and management drugs [1,2,3]
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