Ultrasound-Assisted Synthesis of Novel Chromone-Based Thiosemicarbazone Derivatives as Potential Anticancer Agents and Their Apoptotic, Cell Cycle, Autophagy, Molecular Docking, and ADMET Prediction Studies.

Abstract

A series of novel chromone derivatives bearing a thiosemicarbazone moiety (3a-i and 5) at the C-3 position was efficiently synthesized using ultrasound irradiation. The compounds were evaluated for in vitro cytotoxicity against T24 (bladder transitional cell carcinoma) and PC3 (human prostate adenocarcinoma) cell lines. Compounds 3b (R ═ Me) and 3g (R ═ benzyl) exhibited the most potent cytotoxicity, outperforming doxorubicin. These two compounds significantly induced late apoptosis and necrosis, arrested the cell cycle at distinct phases in both cell lines, and demonstrated potential for autophagic induction. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions for them indicated favorable drug-like properties for these compounds, supporting their potential as anticancer agents. Molecular docking studies for both 3b and 3g revealed strong interactions with VEGFR-2 receptor, further highlighting their promise as scaffolds for novel antitumor drug development.