Can a Small Change in the Heterocyclic Substituent Significantly Impact the Physicochemical and Biological Properties of (Z)-2-(5-Benzylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic Acid Derivatives?

Rhodanine-3-acetic acid derivatives are attractive compounds with versatile effects. What is very important is that compounds of this type have many biological properties. They are tested, among others, as fluorescent probes for bioimaging and aldose reductase inhibitors. Rhodanine-3-acetic acid derivatives also have antibacterial, antifungal and anticancer activity. The presented work demonstrates that a slight change in the five-membered heterocyclic substituent significantly affects the properties of the compounds under consideration. Three rhodanine-3-acetic acid derivatives (A-1-A-3) were obtained in the Knoevenagel condensation reaction with good yields, ranging from 54% to 71%. High thermal stability of the tested compounds was also demonstrated above 240 °C. The absorption and emission maxima in polar and non-polar solvents were determined. Then, the possibility of using the considered derivatives for fluorescence bioimaging was checked. Compounds A-1 and A-2 were successfully used as fluorescent dyes of fixed cells of mammalian origin. In addition, biological activity tests against bacteria and fungi were carried out. Our results showed that A-1 and A-2 showed the most excellent antimicrobial activity among the newly synthesized compounds, especially against Gram-positive bacteria.

The assessment of physicochemical properties of Cisplatin complexes with purines and vitamins B group.

The positively charged products of Cisplatin hydrolysis can form bonds with Guanine and Adenine, showing the ability to crosslink with nucleobases within the double helical DNA, and leading to apoptosis of the neoplastic cell. It has been proved that the presence of chemicals other than nucleobases, compound of aromatic rings with a nitrogen lone pair on the ring, such as B vitamins, may have a competitive character in relation to a chemotherapeutic drug. A theoretical study confirms the stability of bonds formed not only between Cisplatin and Guanine/Adenine but also Cisplatin and B vitamins, namely Thiamine (vit.B1), Niacin (vit.B3), Riboflavin (vit.B2) and Pyridoxal phosphate (vit.B6). That is why it seems to be justified to conduct the research on the physicochemical, thermochemical and optical properties of mono and diaqua complexes of Cisplatin with nucleobases and B vitamins. Equally important is carrying out such research as spectroscopic measurements, bond order analysis and vibrational analysis of the studied complexes. The complexation reaction is spontaneous and thermodynamically favored with the high electronegativity value, a shift of the electron density from the metal zone towards organic compounds, a reduction the value of gap parameter and a shift of the maximum absorbance ΔλABS towards longer wavelengths. Moreover, the performed density variation upon photoexcitation showed the contributions from HOMO→LUMO transition, where the maximum of the absorption band shifts towards shorter wavelengths compared to the cisPt derivatives, thereby lowering the photoexcitation energy. The formation of complexes causes the reduction of energy gap (ΔEgap) values and show higher kinetic stability with high values of gap. The bonding energies between Cisplatin and the target molecules were performed. Cisplatin forms the strongest bonds with Guanine and Pyridoxal phosphate (vit.B6). The vibrations of Pt-N7 bond in complexes occur in the low range of frequencies with low intensities. Only in case of nucleobases appeared vibrations of Pt-N7 in high frequencies. The highest intensity is shown by symmetry and asymmetry stretching vibrations of H-O(H2O) bonds in the high range of frequencies. The vibrations related with ammonium groups (NH3) of great importance appear in the medium and high range of frequencies. The complexes with Guanine show the highest intensities. A theoretical IR spectra were studied. The obtained calculated IR spectra for native nucleobases and vitamins from B group were compared with their experimental FT-IR. So the conducted research provides theoretical knowledge in practical terms regarding the physicochemical and spectral properties of the formed Cisplatin complexes with both nucleobases and B vitamins. Theoretical and partially experimental studies of the molecular and electronic structure or prediction of spectroscopic characteristics are quite useful for better understanding of the reactivity of this drug with physiological target molecules.

The Affinity of Carboplatin to B-Vitamins and Nucleobases.

Platinum compounds have found wide application in the treatment of various types of cancer and carboplatin is one of the main platinum-based drugs used as antitumor agents. The anticancer activity of carboplatin arises from interacting with DNA and inducing programmed cell death. However, such interactions may occur with other chemical compounds, such as vitamins containing aromatic rings with lone-pair orbitals, which reduces the anti-cancer effect of carboplatin. The most important aspect of the conducted research was related to the evaluation of carboplatin affinity to vitamins from the B group and the potential impact of such interactions on the reduction of therapeutic capabilities of carboplatin in anticancer therapy. Realized computations, including estimation of Gibbs Free Energies, allowed for the identification of the most reactive molecule, namely vitamin B6 (pyridoxal phosphate). In this case, the computational estimations indicating carboplatin reactivity were confirmed by spectrophotometric measurements.

Simultaneous Malignant and Benign Nonepithelial Neoplasms of the Larynx-A Case Report and Literature Review.

Nonepithelial tumors of the larynx are relatively rare neoplasms of the head and neck. The chondrosarcoma, which develops commonly from cricoid and thyroid cartilage, stands for 0.2% of the laryngeal malignant neoplasms. The rhabdomyoma is even more uncommon benign tumor developing from the laryngeal striated muscles. The clinical manifestation and the treatment options depend on the histopathological evaluation, tumor localization, and its size. In presented case, the simultaneous occurrence of benign and malignant tumors of mesenchymal origin in the patient's larynx was provoking hoarseness, globus sensation, and dysphagia. To the best of authors' knowledge, no other case of the concomitance of rhabdomyoma and chondrosarcoma of the larynx have been reported in the literature.

Optimizing the optical and biological properties of 6-(1H-benzimidazole)-2-naphthalenol as a fluorescent probe for the detection of thiophenols: a theoretical study.

The study presents the influence of structure modulation by introduction of selected donor and acceptor substituents on the properties of 6-(1H-benzimidazole)-2(2,4-dinitrobenzenesulfonate)naphthalene used in thiophenol identification. The presence of -OH and -OR groups enhances the non-linear optics (NLO) response of the marker. The -NO2 substituent maximizes the non-linear response and increases the amount of transferred charge and the charge-transfer distance. The introduction of the -OH, -NO2 and -CN groups into the marker structure significantly improves the solubility and optical availability. The -NO2 group however contributes to mutagenicity and carcinogenicity. The -OH and -OR groups can be successfully used in bioimaging to detect specific molecules containing the -SH group in their structure. At the same time, the -OR group minimizes the energy barrier necessary to break the bond between the chromophore and the linker. The paper also includes a comparison of optical and biological properties of structures before and after identification of thiophenols.

Synthesis, photophysical and biological properties of a new oxazolone fluorescent probe for bioimaging: an experimental and theoretical study.

In this study, a new oxazolone derivative 4-{N,N-bis[2-phenyl-4-benzylidene-1,3-oxazol-5(4H)-one]amino}benzaldehyde (PB3) was synthesized and investigated as a fluorescent dye. The spectroscopic properties in different solvents were thoroughly studied. The experimental data were supported by quantum-chemical calculations using density functional theory. Measurements and theoretical calculations showed that the PB3 dye is characterized by non-monotonic solvatochromism, a strongly polar charge transfer excited state, a large Stokes' shift, a high fluorescence quantum yield and a high fluorescence lifetime. Bioconjugate complexes (PB3-concanavalin A) were studied by circular dichroism (CD) spectroscopy. The results showed that the secondary structure of concanavalin A was not significantly influenced by the PB3-fluorophore. Conventional fluorescence microscopy imaging of Candida albicans cells, incubated with the PB3-concanavalin A, was demonstrated. The results from cytochemistry experiments demonstrate that the PB3 dye has valuable advantages compared to the other long-wavelength dyes in typical fluorescence-based cell labeling applications. In vitro tolerance was evaluated by the MTT method in the human colon adenocarcinoma cell line HT29. The PB3 and bioconjugate complexes (PB3-concanavalin A), in the range of concentrations tested, were not considerably toxic. The AutoDock simulations showed LYS46 as the most likely active site for covalent bond formation during PB3-concanavalin A conjugation. In addition, theoretical studies have shown that PB3 is characterized by good bioavailability and absorption/transmission across the cell membrane. This molecule will not bioaccumulate in living organisms and should be excreted in urine without interacting with other drugs. This work provided promising results for the red fluorescent probe (PB3) as a valuable alternative to commercial probes designed for cellular labeling in biological and biomedical research.