Synthesis, DNA interaction, in vitro/in silico topoisomerase II inhibition and photodynamic therapy activities of two cationic BODIPY derivatives

Abstract

A new series of BODIPY 3 and 6 with two dimethylamino and diethylamino moieties at their 3,5-positions were prepared via Knoevenagel condensation of BODIPY 2 and 5 with 3,4-bis{3-[3-(dimethylamino)phenoxy]propoxy}benzaldehyde and 4-{3-[3-(dimethylamino)phenoxy]propoxy}benzaldehyde. Water soluble BODIPY-3a and BODIPY-6a were synthesized by treating BODIPY 3 and 6 with an excess of CH3–I in DMF. Singlet oxygen quantum yields, DNA binding and cleavage, topoisomerase II inhibition and photodynamic therapy activities of two cationic BODIPY derivatives (BODIPY-3a and BODIPY-6a) were examined utilizing different methods. The singlet oxygen quantum yield values of compounds were found to be 0.07 and 0.13 in TBS. BODIPY-3a and BODIPY-6a interacted with CT-DNA with Kb values of 5.18±(0.15) × 103 and 2.88±(0.05) × 103 M−1, respectively. The agarose gel electrophoresis experiments indicated that BODIPY-3a and BODIPY-6a had marked photocleavage activities on supercoiled plasmid DNA. The topoisomerase II inhibition studies showed that BODIPY-6a had higher inhibitory effect than BODIPY-3a, which was in line with the theoretical DNA-topoisomerase complex binding studies via molecular docking method. Based on MTT assay results, the IC50 values of BODIPY-3a and BODIPY-6a ranged from > 100 μM to 27.20 μM for 24, 48 and 72 h without and with light irradiation. Finally, LpBODIPY-6a and NpBODIPY-6a were prepared and their cytotoxic and phototoxic properties were determined using MTT assay. The IC50 values of LpBODIPY-6a were found > 100 μM and 33.63 μM, while the IC50 values of NpBODIPY-6a were 26.01 μM and 5.66 μM without/with irradiation. The presented studies suggested that nanoparticle formulation was found the most promising delivery vehicle for BODIPY-6a.