Synthesis, Structure and Impact of 5-Aminoorotic Acid and Its Complexes with Lanthanum(III) and Gallium(III) on the Activity of Xanthine Oxidase.

Lozan Todorov,Luciano Saso,Abderahmane Linani,Khedidja Benarous,Irena Kostova,Maria Traykova

doi:10.3390/molecules26154503

Abstract

The superoxide radical ion is involved in numerous physiological processes, associated with both health and pathology. Its participation in cancer onset and progression is well documented. Lanthanum(III) and gallium(III) are cations that are known to possess anticancer properties. Their coordination complexes are being investigated by the scientific community in the search for novel oncological disease remedies. Their complexes with 5-aminoorotic acid suppress superoxide, derived enzymatically from xanthine/xanthine oxidase (X/XO). It seems that they, to differing extents, impact the enzyme, or the substrate, or both. The present study closely examines their chemical structure by way of modern methods—IR, Raman, and 1H NMR spectroscopy. Their superoxide-scavenging behavior in the presence of a non-enzymatic source (potassium superoxide) is compared to that in the presence of an enzymatic source (X/XO). Enzymatic activity of XO, defined in terms of the production of uric acid, seems to be impacted by both complexes and the pure ligand in a concentration-dependent manner. In order to better relate the compounds’ chemical characteristics to XO inhibition, they were docked in silico to XO. A molecular docking assay provided further proof that 5-aminoorotic acid and its complexes with lanthanum(III) and gallium(III) very probably suppress superoxide production via XO inhibition.

Highlights

The importance of the superoxide radical, O2 −, for human health and disease has been known for a long time [1,2,3]
The nature of Ga(III) and La(III) complexes was confirmed by IR, Raman, and 1 H NMR spectroscopy
The relative differences between the superoxidescavenging activities of these compounds were in agreement with their previously observed affinity to participate in interactions with stable free radicals via electron transfer reactions [54,55]

Summary

Introduction

The importance of the superoxide radical, O2 − , for human health and disease has been known for a long time [1,2,3] It plays a crucial role in normal biological processes [4,5,6,7,8] as well as in the initiation of pathological conditions [9,10,11,12,13,14,15,16]. The formation of O2 − is inevitable in the living body It is involved in a number of normal physiological processes as well as in cellular malignization, tumor proliferation, and malignant cell death [20,21]. It is capable of helping eradicate malignant cells by varying their redox homeostasis

Methods

Results

Conclusion