Evaluation of antiproliferative activity, acute activity, and anticancer activity of three quinazolinone-based hydroxamic acids in a white mouse mode

Abstract

The study investigated the antiproliferative activity, acute toxicity, and anticancer potential of three quinazolinone-based hydroxamic acid derivatives using in vitro and in vivo models. Cytotoxicity against the HEK-293A cell line was evaluated using the MTT assay, revealing IC₅₀ values ranging from 1.00 to 2.83 µg/ml. These results indicate moderate to strong antiproliferative activity. Acute toxicity was assessed in ICR mice to determine the safety profiles of the compounds. Compound 14a exhibited moderate toxicity with an LD₅₀ of 1504.17 mg/kg, whereas compound 14i showed no significant toxic effects at doses up to 5000 mg/kg, demonstrating a favorable safety margin. Anticancer efficacy was further examined in a white mouse tumor model. Treatment with compound 14a at 100 mg/kg did not inhibit tumor, while compound 14i administered at doses of 250 and 500 mg/kg significantly reduced tumor progression compared with the control group. These findings indicate that compound 14i possesses promising anticancer activity combined with low acute toxicity, supporting its potential for further preclinical development as a safe and effective anticancer agent.