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

Barut B., COBAN O., YALÇIN C. Ö., Bas H., SARI S., Biyiklioglu Z., ...More

DYES AND PIGMENTS, vol.174, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 174
  • Publication Date: 2020
  • Doi Number: 10.1016/j.dyepig.2019.108072
  • Journal Name: DYES AND PIGMENTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chimica, Communication Abstracts, Compendex, INSPEC, Metadex, Civil Engineering Abstracts
  • Keywords: Synthesis, BODIPY, Colorectal, Molecular docking, Topoisomerase, Nanoparticle, COMBINATION THERAPY, PHTHALOCYANINES, NANOPARTICLES, ZINC(II), BINDING
  • Karadeniz Technical University Affiliated: Yes


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 K-b values of 5.18 +/-(0.15) x 10(3) and 2.88 +/-(0.05) x 10(3) 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 mu M to 27.20 mu M 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 mu M and 33.63 mu M, while the IC50 values of NpBODIPY-6a were 26.01 mu M and 5.66 mu M without/with irradiation. The presented studies suggested that nanoparticle formulation was found the most promising delivery vehicle for BODIPY-6a.