Current Organic Synthesis - Online First

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.

Soil sample pretreatment is a critical step in soil analysis, often involving complex processes and the use of organic solvents, which can lead to environmental pollution and inefficiency. In this regard, traditional methods are time-consuming and prone to human error, rendering them unsuitable for large-scale soil surveys. To address these challenges, this study proposes a novel rapid soil pretreatment method employing a device that integrates ultrasonic extraction with pure water and capillary electrophoresis using capacitively coupled contactless conductivity detection (CE-C4D). This study aims to enhance the efficiency and accuracy of soil nutrient analysis while minimizing environmental impact.

Ultrasonic extraction using pure water as a solvent, combined with CE-C4D detection, was employed for rapid and efficient analysis of soil nutrients, particularly potassium and phosphorus. Parameters influencing ultrasonic extraction, including frequency, treatment time, and the relationship between solution factors and cavitation yield, were optimized through both simulations and experiments. Cavitation yield was assessed using iodine release, conductivity measurement, and fluorescence analysis. Additionally, the sound pressure distribution within the extraction tube was simulated, and temperature changes during ultrasonic treatment were monitored. The pretreatment device and detection method were validated using standard soil samples.

The optimal ultrasonic extraction parameters were identified as a frequency of 1.7 MHz and a treatment time of 10 minutes, resulting in the most effective cavitation yield. The use of pure water as a solvent improved both the efficiency of soil pretreatment and the environmental sustainability of the process. The CE-C4D system successfully detected available potassium and phosphorus in standard soil samples with high accuracy, showing trends consistent with standard values and relative standard deviations (RSD, n=4) of less than 5%. Blind tests on soil samples also demonstrated minimal error, with RSD (n=4) below 4%.

This study presents a portable and efficient ultrasonic extraction device for soil pretreatment coupled with a custom-designed CE-C4D detector for the rapid analysis of available potassium and phosphorus. The use of pure water as a solvent significantly reduces environmental impact, simplifies the process, and enhances testing efficiency, reducing the required testing time from 15-20 days to within 30 minutes. This innovation provides a reliable solution for on-site soil analysis, offering potential applications in large-scale soil surveys and routine soil testing.

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.

Ripasudil hydrochloride or 4-Fluoro-5-{[(2S)-2-Methyl-1,4-diazepan-1-yl] sulfonyl isoquinoline hydrochloride known as K-115 is used for the treatment of glaucoma and ocular hypertension. In the API industry, to achieve and ensure the quality of drug substances, there is a need for impurity identification, synthesis, and characterization. The impurities are formed during the process, either side reaction or degradation or carried over from the starting material.

The present study explores two new process impurities of Ripasudil Hydrochloride dihydrate, specifically Impurity-1(4-fluoro-5-{[(3R)-3-methyl-4-(2-nitrolbenzenesulfonyl)-1,4-diazepan-1-yl] sulfonyl} isoquino line) and Impurity-2 (4-fluoro-N, N-dimethyl isoquinoline-5-sulfonamide). These impurities are critical to the quality of both the drug substance and the final drug product.

The API crude samples were subjected to LC-mass spectrometry for the identification of unknown impurities and further based on the observed mass values, a strategic synthetic route was designed for the synthesis of unknown impurities. The synthetic routes for these impurities were developed to avoid column purification, achieving high yields and purity.

The above synthesized impurities were subjected to spectral analysis like mass spectrometry, ¹H NMR, and ¹³C NMR and confirmed the desired structure of the unknown impurities. So, as far as we know, the two impurities are new process impurities and have not been reported in the literature.

The two new process impurities have been prepared and used as impurities for the method development and quality evaluation of the Ripasudil drug substance. Given the regulatory significance of Ripasudil hydrochloride, our successful synthesis and characterization efforts have proven to be valuable. This research offers valuable insights into the generic pharmaceutical industry

L-type amino acid transporter-1 is a drug that stimulates the functions of the brain’s central nervous system. Membrane transporters have evolved, leading to a distinct approach in L-type amino acid transporter-1 drug delivery. One of the transporters used for transporting drugs across biological membranes is the L-type amino acid transporter-1. It is widely discussed in the medicinal field.

Numerous investigations indicate a close connection between the properties of alkanes and the diversity of central nervous system drugs in the brain, specifically log P and molecular weight. One important study that analyzes structural properties is focused on topological descriptors. Recently, topological indices have found application in the development of quantitative structure-activity relationships. These indices are correlated with the physicochemical properties of BCNS-acting drugs and their biological activity.

The study employs significant methods of calculating topological indices: the edge set partition method and the Djokovi´c-Winkler relation (cut method) are utilized to calculate the values of these descriptors.

The results of distance and degree-based topological descriptors have been derived. The strong correlation between topological descriptors and the physicochemical properties of BCNS-acting drugs has been studied.

This article identifies important topological features for various CNS medications, aiming to support researchers in understanding the properties of molecules and their biological activity. Furthermore, we demonstrate how strongly these behaviors correspond to the physicochemical properties of central nervous system drugs.