Chemical Reactivity Theory and Empirical Bioactivity Scores as Computational Peptidology Alternative Tools for the Study of Two Anticancer Peptides of Marine Origin

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 6; p. 1115
• Main Authors: Frau, Juan, Flores-Holguín, Norma, Glossman-Mitnik, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.03.2019; MDPI
• Subjects: AGEs inhibition ability; Amino acids; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aquatic Organisms - chemistry; bioactivity scores; Biological activity; Cancer; Chemical interactions; Chemical reactions; chemical reactivity theory; Computational chemistry; Computer applications; Drugs; Glycation End Products, Advanced - chemistry; Glycation End Products, Advanced - pharmacology; Glycosylation; Models, Molecular; Molecular Conformation; Molecular docking; Molecular structure; Peptides; Peptides - chemistry; Peptides - pharmacology; Pharmaceutical sciences; pKa; Reactivity; soblidotin; Software; Structure-Activity Relationship; tasidotin; tasidotin; AGEs inhibition ability; soblidotin; bioactivity scores; chemical reactivity theory; pKa
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24061115

This work presents an account of the reactivity behavior of the anticancer marine drugs, Soblidotin and Tasidotin, based on the calculation of the global and local descriptors resulting from Chemical Reactivity Theory (CRT), also known as Conceptual DFT, for their consideration as a useful complement to approximations based on Molecular Docking. The information on the global and local reactivity descriptors of the Soblidotin and Tasidotin molecules, obtained through our proposed methodology, may be used for the design of new pharmaceutical analogs by relying on the chemical interactions between these peptides and their protein-type biological receptors. It can be concluded that the CRT approximation to the global and local chemical reactivity, based on the descriptors, can provide interesting information for the consideration of both molecules as potential therapeutic drugs. This is complemented by a study on Advanced Glycation Endproduct (AGE) inhibition, by comparison with the usual molecular systems considered for the task, as a re-purposing study. Finally, the bioactivity scores for Soblidotin and Tasidotin are predicted through an empirical procedure, based on comparison with molecular structures with well-known pharmacological properties.