Structural Study of a La(III) Complex of a 1,2,3-Triazole Ligand with Antioxidant Activity.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lanthanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels, and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculated/experimental IR and Raman spectra. The best DFT method appeared to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. The potential free radical scavenging activity of both the ligand and the complex was investigated in several radical-generating model systems. The potential mechanisms of antioxidant action (hydrogen atom transfer (HAT) and single-electron transfer (SET)) were elucidated.

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs.

Since the accidental discovery of the anticancer properties of cisplatin more than half a century ago, significant efforts by the broad scientific community have been and are currently being invested into the search for metal complexes with antitumor activity. Coordination compounds of transition metals such as platinum (Pt), ruthenium (Ru) and gold (Au) have proven their effectiveness as diagnostic and/or antiproliferative agents. In recent years, experimental work on the potential applications of elements including lanthanum (La) and the post-transition metal gallium (Ga) in the field of oncology has been gaining traction. The authors of the present review article aim to help the reader "catch up" with some of the latest developments in the vast subject of coordination compounds in oncology. Herewith is offered a review of the published scientific literature on anticancer coordination compounds of Pt, Ru, Au, Ga and La that has been released over the past three years with the hope readers find the following article informative and helpful.

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

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.

Does dihydropyrimidine dehydrogenase level modify plasma antioxidant capacity in colorectal cancer patients treated with fluoropyrimidines?

INTRODUCTION: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD). AIM: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen. MATERIALS AND METHODS: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study. RESULTS: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients' plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases. CONCLUSIONS: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals' antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient's oxidative status.

In Vitro Interaction of 5-Aminoorotic Acid and Its Gallium(III) Complex with Superoxide Radical, Generated by Two Model Systems.

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.

Developments in the Application of 1,2,3-Triazoles in Cancer Treatment.

BACKGROUND: The impact of cancer on modern society cannot be emphasized enough in terms of both economic and human costs. Cancer treatments are known, unfortunately, for their side effects - frequently numerous and severe. Drug resistance is another issue medical professionals have to tackle when dealing with neoplastic illnesses. Cancer rates are rising worldwide due to various factors - low-quality nutrition, air and water pollution, tobacco use, etc. For those and many other reasons, drug discovery in the field of oncology is a top priority in modern medical science. OBJECTIVE: To present the reader with the latest in cancer drug discovery with regard to 1,2,3-triazole- containing molecules in a clear, concise way so as to make the present review a useful tool for researchers. METHODS: Available information present on the role of 1,2,3-triazoles in cancer treatment was collected. Data was collected from scientific literature, as well as from patents. RESULTS: A vast number of triazole-containing molecules with antiproliferative properties have been proposed, synthesized and tested for anticancer activity both in vitro and in vivo. The substances vary greatly when considering molecular structure, proposed mechanisms of action and affected cancer cell types. CONCLUSION: Triazole-containing molecules with anticancer activity are being widely synthesized and extensively tested. They vary significantly in terms of both structure and mechanism of action. The methods for their preparation and administration are well established and with proven reproducibility. These facts suggest that triazoles may play an important role in the discovery of novel antiproliferative medications with improved effectiveness and safety profile.

Lanthanum, Gallium and their Impact on Oxidative Stress.

The role metals play in living organisms is well established and subject to extensive research. Some of them participate in electron-exchange reactions. Such reactions cause generation of free radicals that can adversely impact biological systems, as a result of oxidative stress. The impact of 'non-biological' metals on oxidative stress is also a worthy pursuit due to the crucial role they play in modern civilization. Lanthanides (Ln) are widely used in modern technology. As a result, human exposure to them is increasing. They have a number of established medical applications and are being extensively researched for their potential antiviral, anticancer and anti-inflammatory properties. The present review focuses on lanthanum (La) and its impact on oxidative stress. Another metal, widely used in modern high-tech is gallium (Ga). In some respects, it shows certain similarities to La, therefore it is a subject of the present review as well. Both metals exhibit ionic mimicry which allows them to specifically target malignant cells, initiating apoptosis that makes their simple salts and coordination complexes promising candidates for future anticancer agents.