Green Production of Indolylquinones, Derivatives of Perezone, and Related Molecules, Promising Antineoplastic Compounds

Abstract

A green approach to produce the indolyl derivatives from four natural quinones (perezone, isoperezone, menadione, and plumbagin) was performed; in this regard, a comparative study was accomplished among the typical mantle heating and three nonconventional activating modes of reaction (microwave, near-infrared, and high speed ball milling or tribochemical), under solventless conditions and using bentonitic clay as a catalyst. In addition, the tribochemical production of isoperezone from perezone is also commented on. It is also worth noting that the cytotoxicity of the synthesized indolylquinones in human breast cancer cell was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, with the 3-indolylisoperezone being the most active. The structural attribution of the target molecules was performed by typical spectroscopic procedures; moreover, the experimental and computed1H and13C NMR chemical shifts data, with previous acquisition of the corresponding minimum energetic structures, were in good agreement.

Computational Characterization of Perezone, Isoperezone and their Sulfur‐Derivatives: Anti‐inflammatory Activity.

“…Similar behavior was observed with the isoperezone derivatives in C1=O1, C1‐C2, C2‐C3, C3‐C4 and C5‐C6. This change of geometrical parameters has been also reported for others quinonic derivatives …”

“…Table shows the atomic charges of the perezone and isoperezone sulfur derivatives. The theoretical calculations, evaluated by the scheme of Natural Populations Analysis (NPA), indicated that the most negative charge is localized on the oxygen atom of the hydroxyl group, appropriately explained by a strong intramolecular hydrogen bond between the hydroxyl group with the adjacent carbonyl group (O−H⋅⋅⋅O=C) in all the target molecules.…”

“…This molecule has been the target of many chemical studies, it has also been used as a pigment showing in addition several pharmacological effects, vg the release of mitochondrial Ca 2+ . In addition, perezone and some of its derivatives are able to produce cytotoxic activity …”

In silico Study of the Pharmacologic Properties and Cytotoxicity Pathways in Cancer Cells of Various Indolylquinone Analogues of Perezone

“…As a part of our ongoing research interest in the implementation of green synthetic strategies to synergize and modify the pharmacological activities of single known compounds through the construction of novel hybrid molecules [ 17 , 18 , 19 , 20 , 21 , 22 ], in a recent work, we reported the cytotoxic effects on a human breast cancer cell line of a set of four indolylquinones 1 – 4 obtained from perezone, isoperezone, plumbagine and menadione, respectively [ 23 ]. Based on the corresponding cytotoxicity IC 50 values the studied compounds could be ranked as follows: indolylisoperezone > indolylplumbagine > indolylperezone > indolylmenadione, i.e., 2 was the most active compound and 4 the least active, while 1 was less active than 3 .…”

A DFT Study of the Geometrical, Spectroscopical and Reactivity Properties of Diindolylmethane-Phenylboronic Acid Hybrids

“…Thus, the GIAO methodology and Tomasi’s polarizable continuum model (PCM) were used, considering the agreement among experimental and theoretical data observed in previous works [ 30 , 31 ]. However, in this case, the linear regression analysis of the data set of 1 H-NMR shifts with the gas phase data, provided a regression coefficient of 0.1047, indicating a disagreement in the theoretical and experimental data.…”