Global reactivity indexes and nonparametric statistics in the study of the proapoptotic activity of coumarins

Abstract

Coumarins are widely distributed as secondary metabolites and are popular structural motifs among known anticancer agents; their planarity and electronic environment are very important building blocks for bioactive compounds. Due to the broad scope of their biological activity, anticancer properties of these molecules remain an important goal for medicinal chemistry. In this work, the knowledge and understanding of the correlation between electronic environment and global reactivity of a series of hydroxycoumarins lead to develop a statistical model to study the proapoptotic activity of this type of compounds. Thus, the analysis of the charge distribution within the molecule and experimental data of proapoptotic activity of known coumarins are analyzed through a regression model. This model offers the possibility of predicting whether a structural related coumarin will show the desired activity or not, which increases the ability to a target‐directed approach in the development of anticancer therapeutic agents.

Study of Local Reactivity of Isatoic Anhydride Applying Quantum Molecular Similarity

“…[12] In addition, the relationship between s with a variety of descriptors has been already applied to other molecules. [13][14][15][16][17] The original idea is centred on the study of the behaviour of a similarity measure defined by the Euclidean distance, established in a three-dimensional space. Thus, the substituted molecules of benzoic acid are represented by three-dimensional vectors, the quantum fingerprint, whose components are the QTAIM descriptors evaluated at the Bond Critical Points (BCP) of the corresponding bond paths; Popelier calls this set, the BCP three-dimensional space.…”

Mannich bases of hydroxycoumarins: synthesis, DFT/QTAIM computational study and assessment of biological activity

“…For these derivatives, it has been recognized that the position of the hydroxy substituents within the coumarin structure plays an important role for its biological activity [6][7][8] and, in the quest of nding a specic and oriented activity in certain pathways of neoplastic disease, some studies have been made to relate their electronic density distribution with their antineoplastic activity. 9,10 On another hand, their highly delocalized p conjugated system, their planarity, their electronic environment and the feasibility for modifying their substitution pattern, have made them extensively studied, both theoretically 11 and experimentally, resulting in a ne tuning of their electronic properties, 12 yielding interesting applications of their photophysical properties in materials chemistry and light-driven biologically signicant processes, such as photodynamic therapy (PDT) 13,14 and uorescent probes for many relevant analytes. 15 Concerning functionalized hydroxycoumarins, Mannich bases of 7-hydroxycoumarins are the products of the Mannich reaction, which is a classical, yet important electrophilic substitution reaction used as a synthetic tool in aromatic heterocyclic chemistry yielding a growing number of interesting compounds with potential in medicinal chemistry.…”