Novel water soluble BODIPY compounds: Synthesis, photochemical, DNA interaction, topoisomerases inhibition and photodynamic activity properties

• Published in: European journal of medicinal chemistry 2019-12, Vol.183, p.111685, Article 111685
• Main Authors: Barut, Burak, Yalçın, Can Özgür, Sari, Suat, Çoban, Özlem, Keleş, Turgut, Biyiklioglu, Zekeriya, Abudayyak, Mahmoud, Demirbaş, Ümit, Özel, Arzu
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; BODIPY; Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Boron Compounds - pharmacology; Cell Line, Tumor; Colorectal; Colorectal Neoplasms - drug therapy; DNA Cleavage - drug effects; DNA Topoisomerases - metabolism; Humans; Molecular Docking Simulation; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Topoisomerase Inhibitors - chemical synthesis; Topoisomerase Inhibitors - chemistry; Topoisomerase Inhibitors - pharmacology; Water
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2019.111685

In this study, BODIPY compounds (2, 3, 5 and 6) bearing 3,4-bis(3-pyridin-3-ylpropoxy)benzyl, 4-(3-pyridin-3-ylpropoxy)benzyl groups were synthesized for the first time and further functionalized in a Knoevenagel condensation reaction with 3,4-bis(3-pyridin-3-ylpropoxy)benzaldehyde and 4-(3-pyridin-3-ylpropoxy)benzaldehyde. The water soluble derivatives of BODIPY compounds (3a and 6a) were synthesized by treating BODIPY compounds 3 and 6 with excess iodomethane in DMF. The photochemical properties and DNA binding modes of 3a and 6a were determined using ct-DNA by UV–Vis spectrophotometer and viscometer. DNA cleavage and topoisomerases inhibition properties were studied DNA using agarose gel electrophoresis. Their topoisomerase inhibition mechanisms were investigated at molecular level and correlations with the in vitro results were searched for using molecular docking method. In addition, cytotoxicity and phototoxicity of both compounds were performed on colorectal cancer cells (HCT-116) using MTT assay for 24 h. Annexin V-FITC/PI test was performed to determine the cell death mechanism of 6a induced by irradiation. Finally, 6a-loaded liposomes (LP6a) and PLGA nanoparticles (NP6a) were prepared and their cytotoxic and phototoxic effects were evaluated by MTT assay. The results claimed that 6a had great potential as photosensitizer agent for colorectal cancer owing to its photochemical, DNA interaction and phototoxic properties. [Display omitted] •Synthesis of water soluble 3a and 6a.•Photochemical studies and DNA interaction of water soluble 3a and 6a.•Topoisomerase I, II inhibitory effects of water soluble 3a and 6a.•Phototoxic effect of 3a and 6a on HCT-116 cells.•Preparation of 6a-loaded LP and PLGA NP and their phototoxic effects on HCT-116 cells.