Future Journal of Pharmaceutical Sciences最新文献

Background

As of 2025, the World Health Organization (WHO) reports that cancer remains a leading cause of death globally. The global Healthy Life Expectancy (HALE) at birth was estimated at 63.5 years in 2019, reflecting the average number of years a person can expect to live in full health. Chronic diseases like cancer significantly impact HALE, underscoring the need for effective interventions. The epidermal growth factor receptor (EGFR) is a validated therapeutic target, especially in cancers with EGFR overexpression or mutations. EGFR tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved clinical outcomes; however, resistance and limited efficacy in some patients demand the development of novel inhibitors. Heterocyclic scaffolds, such as thiazole and pyrazole, have garnered attention for their broad-spectrum anticancer properties, including EGFR inhibition. The synthesis of hybrid molecules combining thiazole and pyrazole cores has further enriched the scope of potential EGFR-targeted anticancer agents.

MainText

This review presents an in-depth analysis of thiazole, pyrazole, and their hybrid derivatives as promising EGFR-TKIs. We have summarized literature from 2008–2025, highlighting structure–activity relationship (SAR) trends, biochemical assay outcomes, and computational insights. The most potent compounds demonstrated submicromolar IC₅₀ values against EGFR and robust cytotoxicity in various cell lines. Conversely, least potent analogs often lacked these structural features or bore bulky or electron-donating groups at critical positions. Biochemical assays confirmed selective EGFR inhibition, while molecular docking and dynamics studies supported the favorable binding profiles of active compounds within the ATP-binding pocket of EGFR.

Conclusion

Thiazole, pyrazole, and their hybrids represent a promising class of EGFR-targeted anticancer agents. A combination of rational SAR-based modifications, supportive biochemical assay results, and computational modeling has laid the foundation for their further optimization. Continued efforts in hybrid design, guided by structural insights, may lead to the development of next-generation EGFR-TKIs capable of overcoming current therapeutic limitations.

Graphic abstract

Background

The present study aims to improve safety and quality assurance of swimming pools located in Sharkia governorate, Egypt. A total of 144 water samples were collected from eight pools. The water quality of the tested pools was assessed according to national swimming pool quality standards in terms of physiochemical and microbial characterization. Microbial contamination was assessed by the detection and enumeration of standard indicator organisms. 16S rDNA sequencing and phylogenetic analysis were utilized for further identification of most resistant bacterial isolate. Antimicrobial susceptibility to various natural potentially antimicrobial agents; including aqueous, alcoholic plant extracts and essential oils was conducted. Both MIC and MBC for tested natural antimicrobial agents were determined. Finally, field application of the most effective antimicrobial agents was carried out to highlight the cons and pros of their usage in field, in order to possess a broader scope of both theoretical and practical aspects of this study.

Results

In terms of physical analysis; 82.9% of tested samples were nonconformed to temperature standard, while 100% were conformed to color and odor. Regarding chemical analysis; 54.3% and 53.3% of samples were nonconformed to alkalinity and combined chlorine, respectively. Assessment of microbial contamination indicated the prevalence of Pseudomonas aeruginosa as a main contaminator of tested pool water (57.1%) followed by total coliforms which ranked second among detected microorganisms (52.4%). Upon performing antimicrobial susceptibility testing of plant extracts and essential oils, cinnamon hot water extract and essential oil showed narrowest MIC ranges. Upon testing various combinations between different tested antimicrobial agents, combination of cinnamon hot water extract and clove essential oil was identified as a promising synergetic combination against resistant isolates. In field application of the most effective antimicrobial compounds resulted in that compatibility markedly decreased for physical standards and slightly for chemical standards. However, microbial pollution was totally eliminated after treatment, which was considered and discussed within the context of the study.

Conclusion

This study targeted full assessment of pools water in Egypt, one of the most prominent findings of this study is prevalence of P. aeruginosa as the main resistant microorganism responsible for microbial pollution of pool water. Cinnamon hot water extract and clove essential oil were identified as the most effective natural antimicrobial agents used in the study. Field application of these antimicrobial agents was a significant step confirming the validity and credibility of current results highlighting the pros and cons of practical application of the suggested pool decontaminators.

Acute lymphoblastic leukaemia (ALL) is a crippling childhood cancer where usually a rare white blood cell runs amok, multiplying uncontrollably. Pegasparaginase, a vital weapon in the ALL arsenal, starves leukaemic cells by depleting asparagine, their lifeline. However, current treatments are plagued by issues like debilitating hypersensitivity, fleeting enzyme stability, and inadequate delivery methods. This review explores groundbreaking solution, the immobilization of pegasparaginase using fungal chitosan for direct intravenous administration. Cutting-edge computational modeling to optimize the enzyme–nanoparticle interaction ensures potent and long-lasting activity. IoT and IoMT integration with smart sensor would enable improved efficiency, decision making, and remote monitoring, while AI and ML can be utilized for drug discovery processes, optimizing drug design for therapeutic applications and forming nanomedicine-based treatment outcomes, respectively. Key parameters like enzyme loading, cross-linking density, and nanoparticle size were meticulously adjusted for peak therapeutic performance. The encapsulation process shields pegasparaginase from the harsh realities of the body, enabling controlled release and sustained enzyme activity. This transformed enzyme boasts improved pharmacokinetics, a longer lifespan and reduced hypersensitivity reactions overcoming the crippling limitations of existing therapies. This approach is particularly aligned with the needs of paediatric ALL patients, who are the majority and highly susceptible to side effects of treatment. Chitosan-based fungal nanoparticles offer a superior, controlled, and biocompatible delivery system, maximizing therapeutic potential of pegasparaginase, while minimizing immunogenic risks. To sum up, this study presents a novel and potent strategy for pegasparaginase immobilization, combining computational brilliance with experimental innovation to conquer the most pressing challenges in ALL treatment. These findings strongly suggest the potential of delivery systems to curb adverse reactions and amplify enzyme efficacy, making them a prime candidate for clinical applications. Future research should focus on scaling up production and conducting clinical trials to validate these findings and explore broader applications for enzyme-based therapies in other diseases. This review underscores the immense potential of integrating nanotechnology and permissible biocompatible materials to revolutionize therapeutic approaches in oncology.

Graphical Abstract

Background

The major focus of the research was to optimize and validate an eco-friendly, cost-effective, high-performance and throughput RP-HPLC technique for the quantification of Cinnarizine in marketed formulation and also evaluate intrinsic stability. Further, the proposed analytical method efficiency was compared with three reported methods using green and white algorithmic matrix viz., AES, AGREE, GAPI, RGB and BAGI.

Results

Chromatographic conditions were optimized with Inertsil ODS-3V column (250 × 4.6 mm, 5 μm) with methanol and 0.1% v/v orthophosphoric acid (pH 2.5) in a 95:05 v/v ratio as mobile phase. The analytical wavelength and flow rate were fixed to 254 nm and 0.5 mL min⁻¹, respectively. Inherent stability profile was also carried out as per ICH Q₁A R₂ guidelines. The Cinnarizine was eluted from the column at 3.328 min and the method was validated in accordance with ICH Q₂ R₁. The optimum linearity of the analytical method was fitting over the range of 2–14 µg mL⁻¹ with a correlation constant of 0.9992. The limits of detection and quantification were 0.00621 µg mL⁻¹ and 0.0207 µg mL⁻¹, respectively. The Cinnarizine was found to be stable in acidic, thermal and photolytic conditions. Whereas, maximum degradation has taken place in basic and oxidative degradation. The Greenness and whiteness of the optimized chromatographic conditions were better than those reported methods.

Conclusion

Overall, the optimized RP-HPLC method can be utilized for the quantification of Cinnarizine in the tablet formulation and to generate the stability profile.

Background

Understanding how a disease develops and the factors that influence any deviation from the balance created by the body is critical in tailoring appropriate treatment for each patient. Existing literature discusses each factor separately, and simply touches on the interaction by recognizing its existence. The objective of this study is to delve in to the relationship between the immune system and the gut microbiota, and how they in turn affect each other and ultimately lead to a diseased state.

Methods

To locate relevant published research, a comprehensive search of electronic databases was performed. Eligible studies were chosen based on predetermined inclusion criteria, which included original research publications exploring the link between the immune system and gut microbiome in IBD patients. Data extraction and quality evaluation followed the PRISMA recommendations. The included studies used a variety of techniques, including observational cohort studies, case–control studies, and experimental research.

Results

Changes in systems from homeostatic function include a dysregulated immune response with heightened pro-inflammatory cytokines, disrupted gut barrier permeability due to increased epithelial permeability and disrupted tight junctions, reduced microbial diversity with elevated levels of pathogenic strains and bacteriophages. Short-chain fatty acids which promote gut barrier integrity and possess anti-inflammatory effects are reduced in patients with IBD.

Discussion

Key findings from the literature review emphasize the role of gut microbiota in immunological responses in IBD, as well as the reciprocal impact of immune dysregulation on microbiome composition. Further research is needed to understand the molecular interaction between the immune system and the gut microbiota (Caron et al. in J Crohns Colitis 18:ii3–ii15, 2024. https://doi.org/10.1093/ECCO-JCC/JJAE082).

The aryl hydrocarbon receptor (AHR) ligand, 6-formylindolo[3,2-b]carbazole (FICZ), plays a pivotal role in modulating various biological processes, including circadian rhythms and maintenance of cellular homeostasis. This study aimed to investigate the pharmacokinetics, tissue distribution, and metabolic clearance of FICZ in vivo using high-performance liquid chromatography (HPLC) with fluorescence detection and an ethoxyresorufin-O-deethylase (EROD) assay. FICZ was administered intraperitoneally to rats in varying doses (42.6 µg/kg, 85.2 µg/kg, 127.9 µg/kg, and 426.4 µg/kg) at multiple time points (1, 3, and 6 h). The liver was identified as the primary organ for FICZ distribution, with peak concentrations observed at 1 h, whereas metabolism by cytochrome P450 enzymes, particularly CYP1A1, led to a significant reduction in FICZ levels over time. Additionally, heart, testis, and brain tissues exhibited varying FICZ accumulation patterns, with dose-dependent distribution observed in testes. The findings highlight the tissue-specific pharmacokinetics of FICZ, with its distribution influenced by both dose and exposure time. EROD activity, a marker for CYP1A1 induction, peaked at 3-h post-administration and was inversely correlated with FICZ degradation. The rapid metabolism of FICZ, exacerbated by its susceptibility to photodegradation, complicates the detection and quantification of endogenous FICZ in vivo. This study presents the first comprehensive assessment of FICZ pharmacokinetics and tissue distribution in various rat tissues, including the liver, heart, brain, prostate, and testis, while also exploring its link to CYP1A1 modulation. This study underscores the complexity of FICZ’s pharmacokinetic, suggesting that both dose- and tissue-specific responses play crucial roles in AHR activation and subsequent enzyme activity. These results contribute to a deeper understanding of FICZ’s biological effects, offering insights into its therapeutic potential and toxicological implication.

Background

The present work aims to develop and validate an LC–MS/MS method for the bioanalysis of a fixed-dose combination containing 325 mg of paracetamol and 50 mg of camylofin in human serum.

Results

A selective, sensitive and fast LC–MS/MS method was developed and validated for quantitative bioanalysis of the analytes from human serum, using protein precipitation technique and diphenylamine as an internal standard (IS). Chromatographic separation was performed on Agilent Zorbax SB C18 column (50 mm × 2.1 mm, 5 μm), using a mixture of 0.1% formic acid and methanol (50: 50 v/v) as mobile phase at a flow rate of 0.5 mL/min, with a run time of 6 min. Tandem mass spectrometry (MS/MS) was employed for the analysis, utilising positive ionisation mode and a multiple reaction monitoring (MRM) scan type. The method was established with a linear range of 100–20,000 ng/mL for paracetamol and 0.25–200 ng/mL for camylofin using 200 μL of human serum.

Conclusion

The developed bioanalytical method was validated as per the Bioanalytical Method Validation Guidance for Industry of the United States Food and Drug Administration (US-FDA)-CDER. The developed method is reliable and easy to use and was applied successfully to a clinical pharmacokinetic study involving twelve healthy Indian subjects under fasting and fed conditions.

Purpose

Patients on regular hemodialysis (HD) are at the highest risk of developing anemia. Vitamin D deficiency is more prevalent in HD patients. Recent studies have suggested that improving vitamin D status can reduce both anemia and the need for higher recombinant human erythropoietin (EPO) dosing. This study is to demonstrate the pleiotropic effects of two regimens of cholecalciferol intake on the hemoglobin (Hgb) levels, ferritin levels, transferrin saturation (TSAT), total iron-binding capacity (TIBC) and the erythropoietin sensitivity index (ERI) in HD patients.

Methods

A prospective, randomized, single blinded trial was conducted to evaluate the effect of weekly versus monthly cholecalciferol administration on anemia parameters and erythropoietin sensitivity in hemodialysis (HD) patients. Fifty eligible patients undergoing HD were randomly allocated to receive either weekly doses of 50,000 IU or monthly doses of 200,000 IU cholecalciferol. Various parameters including Hgb levels, ferritin levels, TSAT, TIBC, ERI, and cumulative dose of erythropoietin (EPO) were evaluated both at baseline and at endpoint. This study was registered at Clinicaltrial.gov, identifier number (NCT05922696), registered 2023/06/20 (Retrospectively registered).

Results

Adding weekly or monthly cholecalciferol to standard HD care for three months resulted in a 72% reduction in EPO doses for thirty-six out of fifty patients. Both regimens significantly increased Hgb levels, with the weekly regimen showing a greater increase (+ 2.67 g/dl vs. + 0.70 g/dl; P < 0.001). The weekly regimen also led to a significant increase in TSAT (P = 0.005) and a decrease in ferritin levels (P = 0.03). Moreover, the weekly regimen significantly reduced EPO doses (−11,600 IU vs. −6,160 IU) and ERI (−4.76 vs. −2.68; P < 0.001) compared to the monthly regimen.

Conclusion

Cholecalciferol demonstrated a beneficial impact on anemia in HD patients. Weekly 50,000 IU regimen had better control over Hgb, TSAT, TIBC, EPO dosing, and erythropoietin sensitivity compared to the monthly 200,000IU regimen.

ClinicalTrials.gov registration number: NCT05922696.

Antimicrobial resistance remains a major global public health challenge, contributing to increased mortality rate and treatment failures in an effort to address this growing challenge, the present research work focused on the synthesis and evaluation of new hydrazone scaffold and pyrazoline derivatives (coded HS6–HS10) as potential antimicrobial agents. The target compounds were synthesized via one-pot condensation reactions and characterized using FTIR, ¹H, and ¹³C NMR techniques. Their antimicrobial activities were assessed in vitro against a panel of Gram-positive, Gram-negative bacteria, and fungal strains.  However, their assessment revealed broad spectrum of antimicrobial activity, where the compounds bearing biaryl-substituted hydrazones with electron-donating or electron-withdrawing groups at para- and or meta-positions showed highest potency. However, MIC values of 12.5 mg/mL were observed against clinical isolates such as E. coli, S. typhi, and P. aeruginosa, while S. aureus, B. subtilis, and S. pneumoniae were inhibited at 12.5–25 mg/mL, while MIC values of 50 mg/mL were recorded against Aspergillus niger, indicating weak antifungal activity. The molecular docking studies conducted using target microbial enzymes such as dihydrofolate reductase (DHFR) and squalene epoxidase (SQLE) against the ligands HS7 and HS8 have strong binding affinities towards DHFR (− 9.6 and − 9.4 kcal/mol) and SQLE (− 9.8 and − 10.2 kcal/mol), respectively, outperforming standard reference drugs ciprofloxacin (− 7.4 kcal/mol) and terbinafine (− 9.8 kcal/mol). Meanwhile, the in silico ADME analysis confirmed that all compounds satisfied Lipinski’s rule of five, suggesting favourable drug-like properties. In conclusion, these findings suggest that substituted hydrazone and pyrazoline derivatives possess considerable promising scaffolds for developing better novel antimicrobial agents that are capable of combating resistant pathogens.

Background

Quality by design (QbD) adverts toward gaining of few expected quality with predetermined and desired specifications. Analytical quality by design (AQbD) approach toward the development of analytical method can significantly lead toward the rugged and robust method specially the assessment and risk management compared to traditional approaches. The aim of present study is to develop an analytical method for the estimation of Picroside II in bulk and pharmaceutical dosage form through RP-HPLC assisted by AQbD.

Result

The important critical parameters were methodically optimized by the experimental design space of Box–Behnken, and model graphs were plotted by utilizing Design Expert Software trial version 13.0. The Picroside II separation was successfully done on the HPLC system of Waters equipped through UV-Visible detector on Waters X Bridge RP C18 column having dimensions (4.6 mm × 150 mm, 5.0 μm), mobile phase containing 0.1% formic acid and acetonitrile (77:23%v/v), and rate of flow at 1.0 mL/min. The wavelength for detection was 266 nm; retention time of Picroside II was between 6.0 and 6.2 min with a total duration run time of 10 min. The proposed developed technique was found to be specific, precise (% RSD < 2%), linear (6–14 μg/mL), and robust (% RSD < 1%). Additionally, forced degradation studies were established and the % drug assay was found to be 99.46 ± 0.86% including the results of specificity in terms of peak purity suggesting no interference of any unidentified peak with the chromatographic peak of Picroside II. The results of all the method validation parameters were within the recommended limit of ICH Q2(R1) guidelines. The proposed method was proved to be green as performed by green assessment tools.

Conclusion

The AQbD-based developed method helped in the design and operating space generating with the knowledge of all the method validation characteristics, and the developed RP-HPLC method on the AQbD-based approach was very useful for Picroside II estimation in bulk and pharmaceutical dosage forms.