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.

Degradation of Human Serum Albumin by Infrared Free Electron Laser Enhanced by Inclusion of a Salen-Type Schiff Base Zn (II) Complex.

A salen-type Schiff base Zn(II) complex included in human serum albumin (HSA) protein was examined by UV-Vis, circular dichroism (CD), and fluorescence (PL) spectra. The formation of the composite material was also estimated by a GOLD program of ligand-protein docking simulation. A composite cast film of HSA and Zn(II) complex was prepared, and the effects of the docking of the metal complex on the degradation of protein molecules by mid-infrared free electron laser (IR-FEL) were investigated. The optimum wavelengths of IR-FEL irradiation to be used were based on experimental FT-IR spectra and vibrational analysis. Using TD-DFT results with 6-31G(d,p) and B3LYP, the IR spectrum of Zn(II) complex could be reasonably assigned. The respective wavelengths were 1652 cm-1 (HSA amide I), 1537 cm-1 (HSA amide II), and 1622 cm-1 (Zn(II) complex C=N). Degradation of HSA based on FT-IR microscope (IRM) analysis and protein secondary structure analysis program (IR-SSE) revealed that the composite material was degraded more than pure HSA or Zn(II) complex; the inclusion of Zn(II) complex enhanced destabilization of folding of HSA.

Investigation by DFT Methods of the Damage of Human Serum Albumin Including Amino Acid Derivative Schiff Base Zn(II) Complexes by IR-FEL Irradiation.

An infrared free electron laser (IR-FEL) can decompose aggregated proteins by excitation of vibrational bands. In this study, we prepared hybrid materials of protein (human serum albumin; HSA) including several new Schiff base Zn(II) complexes incorporating amino acid (alanine and valine) or dipeptide (gly-gly) derivative moieties, which were synthesized and characterized with UV-vis, circular dichroism (CD), and IR spectra. Density functional theory (DFT) and time dependent DFT (TD-DFT) calculations were also performed to investigate vibrational modes of the Zn(II) complexes. An IR-FEL was used to irradiate HSA as well as hybrid materials of HSA-Zn(II) complexes at wavelengths corresponding to imine C=N, amide I, and amide II bands. Analysis of secondary structures suggested that including a Zn(II) complex into HSA led to the structural change of HSA, resulting in a more fragile structure than the original HSA. The result was one of the characteristic features of vibrational excitation of IR-FEL in contrast to electronic excitation by UV or visible light.

On the connection between the complexation and aggregation thermodynamics of oxyethylene nonionic surfactants.

Density and sound velocity data for aqueous solutions containing nonionic surfactants of the homologue series of polyoxyethylene(n) nonyl phenyl ethers (NPEn, n = 5 and 40) were analyzed in the absence and presence of beta-cyclodextrin (beta-CD) at 298 K. Thus, the critical micelle concentration of the surfactants and their apparent and partial molar volumes and compressibilities were measured. From a pseudophase separation model, the partial molar volumes and compressibilities of both pure surfactants in the micelle state and those of NPE40 in the monomer phase have been determined directly. For the ternary systems, increases of the molar volumes and compressibilities of NPE5 and NPE40 at infinite dilution and shifts of the cmc were observed compared to the binary systems. Luminescent measurements of the complexation process between NPE40 and beta-CD showed 1:1 + 1:2 (NPEn/2 beta-CD) stoichiometries for the complexes, with thermodynamic equilibrium constants that were in good agreement with previous results for NPE5 in the presence of beta-CD. This resemblance allowed us to use these results to indirectly determine the molar partial properties of NPE5 in the monomer state and understand the changes in the thermodynamic properties of NPE5 due to aggregation. From the aggregation and complexation data, a folding of the surfactants at the monomer state, in which the hydrophobic moieties of NPEn are surrounded by the EO chain, has been found. The oxyethylene group contributions at the monomer and micelle state of the NPEn homologue series have been estimated. The values of the transfer thermodynamic properties of both surfactants and beta-CD at infinite dilution conditions have been discussed in terms of a new extended model, in which the balance between the released water from the cavities of two beta-CDs and the different hydrophobic moieties of the surfactant that enter the macrocycle was considered.