Norfloxacin Derivative with Carbazole at C-7 FQB-1 Induces Cytotoxic, Antiproliferative, and Antitumor Effects in an Experimental Lung Carcinoma Model

<b>Background:</b> Cancer remains a leading cause of morbidity and mortality worldwide. According to the World Health Organization (WHO), lung cancer is the most prevalent type of cancer among both men and women. Despite the various pharmacological and biological treatments available for...

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Main Authors: Alondra Bocanegra-Zapata, Hiram Hernández-López, Socorro Leyva-Ramos, Rodolfo Daniel Cervantes-Villagrana, Marisol Galván-Valencia, L. Angel Veyna-Hurtado, Norma Guadalupe Ramírez Tovar, Damaris Albores-García, Juan Armando Flores de la Torre, Alberto Rafael Cervantes-Villagrana
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/5/664
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Summary:<b>Background:</b> Cancer remains a leading cause of morbidity and mortality worldwide. According to the World Health Organization (WHO), lung cancer is the most prevalent type of cancer among both men and women. Despite the various pharmacological and biological treatments available for lung cancer, their effectiveness has often fallen short, and the side effects can be severe. Therefore, there is an ongoing need to identify and develop novel compounds with enhanced anti-tumor efficacy and improved safety profiles. Research has shown that fluoroquinolone derivatives exhibit a broad cytotoxic spectrum comparable to other drugs used in clinical chemotherapy. <b>Objective:</b> The aim of this work was to synthesize and evaluate the cytotoxic, anti-proliferative, and anti-tumor effects of FQB-1, a novel fluoroquinolone derivative. <b>Results:</b> In silico molecular docking analysis demonstrated a strong interaction between FQB-1 and human topoisomerase, with a binding affinity score of –9.8 kcal/mol. In vitro cytotoxicity and anti-proliferative assays were conducted using the Lewis Lung Carcinoma (LLC) cell line. FQB-1 was tested at concentrations of 2.5, 5.0, 25.0, 50.0, 100.0, and 150.0 µg/mL. Significant cytotoxic and anti-proliferative effects were observed at concentrations of 50–150 µg/mL after 24 h of treatment. To evaluate FQB-1′s efficacy in vivo, a syngeneic tumor model was established in C57BL/6 mice. Treatment with FQB-1 (100 mg/kg) resulted in a marked reduction in tumor volume compared to the untreated control group. Histopathological analysis of tumor tissues from treated animals revealed a decrease in mitotic index and an increase in necrotic regions, indicating compromised tumor viability. <b>Conclusions:</b> FQB-1 exhibits cytotoxic and anti-proliferative effects and can reduce tumor growth while compromising tumor viability.
ISSN:1424-8247