A new series of thiazolyl-pyrazoline derivatives (4a–d, 5a–d 6a, b, 7a–d, 8a, b, and 10a, b) have been designed and synthesized through the combination of thiazole and pyrazoline moieties, starting from the key building blocks pyrazoline carbothioamides (1a–b). These eighteen derivatives have been designed as anticipated EGFR/HER2 dual inhibitors. The efficacy of the developed compounds in inhibiting cell proliferation was assessed using the breast cancer MCF-7 cell line. Among the new synthesized thiazolyl-pyrazolines, compounds 6a, 6b, 10a, and 10b displayed potent anticancer activity toward MCF-7 with IC₅₀ = 4.08, 5.64, 3.37, and 3.54 µM, respectively, when compared with lapatinib (IC₅₀ = 5.88 µM). In addition, enzymatic assays were also run for the most cytotoxic compounds (6a and 6b) toward EGFR and HER2 to demonstrate their dual inhibitory activity. They revealed promising inhibition potency against EGFR with IC₅₀ = 0.024, and 0.005 µM, respectively, whereas their IC₅₀ = 0.047 and 0.022 µM toward HER2, respectively, compared with lapatinib (IC₅₀ = 0.007 and 0.018 µM). Both compounds 6a and 10a induced apoptosis by arresting the cell cycle of the MCF-7 cell line at the G1 and G1/S phases, respectively. Molecular modeling studies for the promising candidates 6a and 10a showed that they formed the essential binding with the crucial amino acids for EGFR and HER2 inhibition, supporting the in vitro assay results. Furthermore, ADMET study predictions were carried out for the compounds in the study.

Four simple, specific, easy, precise and accurate spectrophotometric methods were developed for the first time to examine ciprofloxacin and metronidazole in combination, without having been separated beforehand by the developed methods. Ciprofloxacin and metronidazole were determined by utilizing advanced absorbance subtraction (AAS), spectrum subtraction, bivariate and ratio difference methods. Precision, repeatability, robustness, and accuracy were all determined to be within acceptable levels after each of these procedures underwent validation in accordance with ICH recommendations. Each method’s benefits and drawbacks are illustrated, and the proposed and reported methodologies were statistically compared.

Thiazoles and pyrazolines represent a class of heterocyclic compounds with attractive and considerable interest in medicinal chemistry due to their diverse pharmacological activities. Hybridizing thiazole and pyrazoline moieties has emerged as an innovative approach to drug discovery, enabling the synthesis of novel compounds with enhanced therapeutic potential. The hybridization of thiazole and pyrazoline scaffolds allows for incorporating different functional groups and substitution patterns, which can influence the compound's bioactivity, selectivity, and pharmacokinetic profile. The hybridization of these two heterocyclic moieties has resulted in compounds with diverse pharmacological properties, such as antimicrobial, antitumor, anti-inflammatory, and antioxidant. Furthermore, thiazolyl-pyrazolines' ability to interact with specific molecular targets, such as enzymes, receptors, or signalling pathways, makes them attractive candidates for drug development. This abstract provides an overview of the hybridization strategy and highlights the medicinal chemistry aspects and biological activities of thiazolyl-pyrazolines.

Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are straightforward, specific, easy to use, and provide exact and accurate results. The determination was conducted through the utilization of several approaches, including zero order (dual wavelength, zero crossing, advanced absorption subtraction and spectrum subtraction), derivative (first derivative of zero crossing), ratio (ratio difference, ratio derivative) and mathematical (bivariate, simultaneous equation, and Q-absorbance) techniques. After undergoing validation in accordance with ICH criteria, it was established that each of these methods achieved acceptable levels of precision, repeatability, robustness, and accuracy. The advantages and disadvantages of each method are demonstrated, and the proposed and reported methodologies were statistically compared. Graphical Abstract

A simple, specific, accurate and precise spectrophotometric method was established for simultaneous determination of acetaminophen and caffeine in pure form and in their pharmaceutical formulation commercially known as Panadol Extra®. Spectrum subtraction has been used in simultaneous determination of both drugs without prior separation. Spectrum subtraction method parameters were validated according to ICH guidelines in which accuracy, precision, repeatability and robustness were found in accepted limits (98-102%). The linearity range was 7.5-45 µg/mL for caffeine and 4-22 µg/mL for acetaminophen with correlation coefficients ≥0.9990 for both drugs. Advantages and disadvantages of spectrum subtraction were discussed and statistical comparison between the proposed method and the reference one was performed.