Khaled Abouzid Mohamed Abouzid

Background/Objectives: Direct intratumoral injection of doxorubicin (DOX) can increase local drug exposure, but rapid escape from the tumor limits retention and contributes to systemic toxicity. This study developed a thermoreversible chitosan/β-glycerophosphate (CS/β-GP) hydrogel designed to form an in situ depot and prolong local DOX delivery. Methods: A three-factor Box–Behnken design was used to optimize CS, β-GP, and DOX concentrations against gelation temperature, gelation time, viscosity, and 7-day cumulative release. The optimized formulation was characterized by rheology, injectability, degradation, swelling, porosity, and 4T1 cytotoxicity. Intratumoral retention, plasma and organ biodistribution, antitumor efficacy, body-weight changes, and cardiac toxicity were then evaluated in 4T1 tumor-bearing BALB/c mice. Results: The optimized hydrogel contained 1.684% w/v CS, 6.601% w/v β-GP, and 0.200% w/v DOX, gelled at 36.3 ± 0.55 °C within 1.65 ± 0.28 min, and released 84.66 ± 8.38% of DOX over 7 days. DOX-loaded hydrogel preserved concentration-dependent cytotoxicity. During in vivo studies, hydrogel delivery lowered the observed plasma DOX peak by approximately 55% and retained measurable intratumoral DOX for 168 h, whereas free DOX solution was no longer detectable. Tumor growth suppression was sustained, with tumor volumes of 205.62 ± 36.85 versus 701.69 ± 69.35 mm³ for free DOX solution on day 24. Repeated hydrogel treatment also markedly attenuated cardiac troponin-I (cTnI) and creatine kinase-MB (CK-MB) elevations relative to free DOX solution. Conclusions: Thermoreversible CS/β-GP delivery reshaped DOX exposure from a rapidly dispersing intratumoral dose into a sustained local depot, improving tumor control while reducing the early plasma peak and attenuating cardiac-injury biomarker elevations.

1. Breast cancer is one of the most prevalent cancer types among women worldwide. This returns back to holding a substantial burden on health systems and societies. According to the World Health Or...

Pyrrolopyrimidine has emerged as a privileged scaffold in medicinal chemistry, owing to its synthesis with variable substitutions and the capacity to exhibit potent, diverse pharmacological profiles. In recent years, the development of dual‐target agents has emerged as a research hotspot in cancer therapy, driven by their ability to overcome drug resistance, enhance pharmacokinetic and safety profiles, and improve patient compliance. The current review focuses on the concept of dual‐targeted anticancer agents, with particular emphasis on pyrrolopyrimidine‐based compounds capable of simultaneously modulating two distinct targets within cancer cells. Furthermore, it highlights resistance mechanisms, development strategies, target mechanisms, in vitro activity profiles, in vivo efficacy data, and available clinical findings, providing a comprehensive overview of their therapeutic potential and future prospects in oncology.

1. Estrogen receptor (ER), is a member of the nuclear receptor family of transcription factors; it is involved in numerous biological functions, such as reproduction and bone physiology [1,2]. The ...

To overcome FLT3 mutations, especially ITD, this review highlights dual inhibitors targeting multiple pathways simultaneously and irreversible inhibitors ensuring permanent FLT3 inhibition, alongside effective PROTACs and combination therapies.

Inhibiting the p53‐MDM2 interaction restores the function of the tumour suppressor protein, p53, and offers a promising avenue for anticancer therapies. Herein, a novel series of pyrazoline‐derived compounds was developed and synthesised to serve as potential inhibitors of the p53‐MDM2 interaction. Scaffold hopping was adopted via replacing the cis ‐imidazoline core of Nutlin‐2 with a pyrazoline core, and molecular docking confirmed the binding orientation of the designed compounds at the p53‐MDM2 interaction site. The antiproliferative activities of these compounds were evaluated against the NCI60 cell lines, where compounds 6c , 6d and 9d displayed the highest inhibitory activities. Subsequently, compound 6d was selected for the five‐doses NCI60 cell panel assay to afford a mean GI ₅₀ value of 8.39 μM. Moreover, 6d significantly reduced MDM2 expression and elevated the expression of p53 in an ELISA‐based assay, yielding a biochemical IC ₅₀ value of 13.8 μM against MDM2, which was confirmed by Western blot as well. Cytotoxicity study confirmed the selectivity of 6d towards cancerous cell lines over normal cell lines. Additionally, X‐ray crystallography was used to check the stereochemistry of compound 6d . These newly identified MDM2 inhibitors represent promising candidates for the development of novel targeted anticancer agents.

The escalating threat of antimicrobial resistance calls for novel therapeutic agents. This study employed a ligand-based design approach to develop three series of N-arylpyrrole derivatives (Va-e, VIa-e, and VIIa-e), refined through molecular modeling. Synthesized compounds were evaluated against ESKAPE pathogens, MRSA, and Mycobacterium phlei. Series Va-e showed the most promise, with compounds Vb, Vc, and Ve outperforming levofloxacin against MRSA (MIC = 4 μg/mL vs. 8 μg/mL). Vc also exhibited activity against E. coli, K. pneumoniae, and A. baumannii, and showed significant inhibition against M. phlei (MIC = 8 μg/mL). Compounds were evaluated for antibiofilm and antivirulence properties, targeting resistance mechanisms linked to infection persistence and dissemination. Most exhibited broad-spectrum biofilm inhibition and antivirulence activity. Cytotoxicity studies revealed selectivity for bacterial cells. ADMET studies supported drug-like properties. Docking studies suggested UPPP inhibition as the potential mechanism. SAR analysis was conducted to support future optimizations.