Current Organic Synthesis - Volume 22, Issue 8, 2025

Thiazoles and bis-thiazoles are recognized for their anticancer and antitubercular properties, making them crucial in medicinal chemistry. This study focuses on synthesizing and evaluating novel bis-thiazole derivatives.

Bis-thiosemicarbazone derivative 3 was used as a precursor to synthesize bis-thiazole (6a-f, 12a-h) and bis-thiazolone (9a-d) derivatives through reactions with appropriate reagents. Anticancer activity was screened using the MTT assay on HCT-116 cells, while antitubercular activity was tested using the microplate Alamar blue assay (MABA). The derivatives were synthesized under optimized reflux conditions and characterized using spectroscopic techniques. Biological assays evaluated their therapeutic potential.

The compounds displayed variable cytotoxicity and antitubercular efficacy. Molecular docking studies on dihydrofolate reductase (DHFR) revealed significant interactions, suggesting potential mechanisms of action.

The results highlight the influence of structural features on biological activity, with active compounds showing favorable interactions and docking scores.

Bis-thiazole and bis-thiazolone derivatives exhibit promising anticancer and antitubercular potential, warranting further investigation for therapeutic applications.

Hofmann rearrangement reactions are important organic reactions used to obtain carbamates, which are formed via isocyanate as an intermediate compound. Since carbamates have applications in various fields, such as pharmaceuticals, agricultural chemistry, and herbicides, this research focuses on synthesizing carbamates using environmentally friendly methods like solid catalysts and electrical techniques due to their unique characteristics in enhancing selectivity and minimizing solvents. Additionally, a comparison between the two methods was made.

In this study, two methods were employed to obtain carbamate. The first method utilized heterogeneous catalysis with sodium halide-modified aluminum oxide to achieve a high basic surface area alongside sodium hypochlorite as a safe and inexpensive oxidant. The second method employs electrochemical catalysis using a carbon anode and a zinc cathode, with sodium halides serving as intermediates.

Sodium chloride modified with aluminum oxide demonstrated better results than sodium bromide and iodide. A higher yield of carbamates was obtained in a shorter time and at moderate temperatures. In contrast, in the electrochemical method, sodium bromide demonstrated the best performance, achieving 75% conversion under ambient conditions.

The comparison between the two methods revealed that the electrochemical method significantly outperformed, as it managed to avoid side products and directed the reaction towards the target compound under mild conditions. Whereas the solid catalytic method (Al2O3/NaCl) obtained lower yields and produced side products in a shorter reaction time.

The decreased anticancer activity of paclitaxel was associated with many factors. The inactivity of p53 was one of the important causes. Some chalcones and their derivatives were found to inhibit the MDM2-p53 interaction. Therefore, the conjugation of chalcones with paclitaxel might be an effective strategy for enhancing the antitumor activity of paclitaxel.

Here, three novel chalones, compounds 1a, 1b, and 1c were first designed and synthesized, followed by the conjugation of them with paclitaxel to prepare compounds 2a, 2b, and 2c. The anti-tumor activity of the aforementioned three novel paclitaxel-chalcone conjugates was evaluated by the MTT method, mitochondrial membrane potential analysis, apoptosis assay, and molecular docking.

The MTT assay demonstrated that compound 2a exhibited superior cytotoxicity compared to 2b and 2c toward breast cancer MCF-7 cells and MDA-MB-231 cells, with the differential activity correlating with electronic effects of their chalcone substituents: compound 2a possessed two electron-withdrawing chlorine groups, compound 2b lacked substitution, and compound 2c featured an electron-donating morpholine. Compared to paclitaxel, compound 2a exhibited a 1.7-fold enhancement in cytotoxic activity against MCF-7 cells and a 2.5-fold increase in potency against MDA-MB-231 cells. Further investigation showed that compound 2a could effectively decrease the mitochondrial membrane potential and induce cell apoptosis. Computational docking studies showed compound 2a formed two hydrogen bonds and one π-H interaction with MDM2, with a docking score of -8.5317.

Research findings demonstrate that the designed chalcone derivatives can effectively inhibit MDM2 activity, with the inhibitory potency closely associated with the substituents on the chalcone core. Notably, the introduction of chlorine substituents not only enhances the binding affinity to MDM2 but also improves the antitumor activity of its hybrid with paclitaxel. Molecular docking analysis reveals that the chlorine-substituted chalcone forms a π-H interaction with Gln72 of MDM2, a feature absent in the other two designed chalcone structures. Furthermore, the chlorine substituent may increase the lipophilicity of the hybrid, facilitating cellular uptake and thereby potentiating its anticancer efficacy.

These findings indicated that the conjugation of paclitaxel with chalones might be an effective strategy for strengthening the anticancer activity of paclitaxel.

Over the past decade, tetrazines have emerged as key molecules in metal complexation, anion binding, and molecular recognition. However, limited research has focused on combining tetrazine rings into the polymer backbones.

This research aimed to focus on synthesizing novel 1,2,4,5-polyacetyl-tetrazines through 1,3-dipolar self-cycloaddition. In this process, bis-α-keto-hydrazonoyl compounds, in the presence of a base, were rapidly converted into bisnitrilimine intermediates. These intermediates then underwent head-to-tail self-polymerization via 1,3-dipolar cycloaddition, resulting in the formation of poly(1,2,4,5-polyacetyltetrazines). The polymers were found to be soluble in various organic solvents, resistant to oxidative degradation, and thermally stable. Characterization of these compounds was performed using techniques, such as proton and carbon nuclear magnetic resonance (NMR) spectroscopy and thermogravimetric analysis (TGA).

In this study, polyacetyl-tetrazines were synthesized by employing a [3+3] self-cycloaddition mechanism, involving the reaction of hydrazonoyl compounds to form six-membered tetrazine rings within the polymer backbone.

The synthesis of new polyacetyltetrazines validated the effectiveness of this method. This method will be useful due to its low cost, mild reaction conditions, and the commercial availability of the chemicals. It could potentially offer a novel pathway for synthesizing tetrazine-based polymers with unique properties.

This study investigated many cancer medicines using a wide range of degree sum-based topological indices and entropy. These numerical numbers, commonly referred to as topological indices or molecular descriptors, depict a substance’s molecular structure. They have been successfully used to properly reflect different physicochemical properties in a number of Quantitative Structure-Property Relationship (QSPR) and Quantitative Structure-Activity Relationship (QSAR) research studies.

The purpose of the study was to investigate the relationships between topological neighborhood indices and physicochemical properties using the QSPR model and linear regression methodology.

We employed linear regression methodology within the QSPR model to examine the connections between physicochemical characteristics and topological neighborhood indices.

The results revealed a significant correlation between the neighborhood indices under scrutiny and the physicochemical features of the potential drugs under investigation.

As a result, both neighborhood topological indices and entropy demonstrate potential as valuable tools for future QSPR investigations when evaluating anticancer medications.

In mathematical chemistry (particularly in chemical graph theory), reverse degree-based topological indices provide good correlations with respect to both mathematical and chemical perspectives for the prediction of biological activities of diverse nature with a variety of relationships between physical, chemical, and thermodynamic parameters.

The main aim of this study is to provide the reverse degree-based graph polynomial, along with its corresponding topological indices. The objective of this methodology is to estimate the physical and chemical properties of specific molecular parameters through an innovative approach, biquadratic regression analysis.

Reverse degree-based graph polynomials are utilized to compute various reverse degree-based topological indices. The outcomes of this study are utilized to perform an innovative approach, biquadratic regression analysis, to estimate the various physicochemical properties of NSAID drugs. This approach provides the best approximations for the said properties.

The main focus of the research is the connection between changes in topological indices and physical characteristics. Based on these findings, this article may aid chemists and pharmaceutical industry professionals in the development of novel pharmaceuticals. A similar relationship can be found between topological indices and the physical characteristics of newly discovered medications for treating specific diseases to assess the physical characteristics of those medications. This study provides a QSPR experiment using biquadratic regression models to yield greater estimates for the properties of the NSAIDs.

Through the utilization of Biquadratic regression models, we have discovered that the indices that we have presented have a close relationship with both the chemical and physical parameters.