Acridine/Acridone–Carborane Conjugates as Strong DNA‐Binding Agents with Anticancer Potential
Daria Różycka, Aleksandra Kowalczyk, Marta Denel‐Bobrowska, Olga Kuźmycz, Magdalena Gapińska, Paweł Stączek, Agnieszka B. Olejniczak
Abstract
Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine (30) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propanamido]acridine (29) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.