BODIPY‐Based Photosensitizers as Potential Anticancer and Antibacterial Agents: Role of the Positive Charge and the Heavy Atom Effect

Abstract

Boron‐dipyrromethene derivatives, including cationic and iodinated analogs, were obtained and subjected to physicochemical and in vitro photodynamic activity studies. Iodinated derivatives revealed a substantial heavy atom effect manifested by a bathochromic shift of the absorption band by about 30 nm and fluorescence intensity reduced by about 30–35 times, compared to that obtained for non‐iodinated ones. In consequence, singlet oxygen generation significantly increased with ΦΔ values in the range 0.69–0.97. The in vitro photodynamic activity was evaluated on Gram‐positive Staphylococcus aureus, Gram‐negative Escherichia coli, and on human androgen‐sensitive prostate adenocarcinoma cells (LNCaP). The novel cationic, iodinated BODIPY, demonstrated the highest activity toward all studied cells. An excellent cytotoxic effect was found against LNCaP cells with an IC50 value of 19.3 nM, whereas the viability of S. aureus was reduced by >5.6 log10 at 0.25 μM concentration and by >5.3 log10 in the case of E. coli at 5 μM. Thus, this analog seems to be a very promising candidate for the application in both anticancer and antimicrobial photodynamic therapy.

Novel BODIPYs with dimethylamine substituents and their cationic and iodinated derivatives for anticancer and antibacterial photodynamic therapy

“…All derivatives showed high molar absorption coefficients in the range of 4.54-4.80, favorable for the use in PDT. The non-iodinated BODIPY derivatives 2 and 3 showed low singlet oxygen generation capacity, in contrast to iodinated derivatives 4 and 5, which revealed exceptionally high singlet oxygen generation quantum yields (0.69-0.97) [7]. It is caused by the aforementioned increase in the formation of the triplet state, in which the compound can react with molecular oxygen to form highly reactive singlet oxygen.…”

“…Due to the best photodynamic activity, derivative 5 was also assessed under hypoxic conditions with an oxygen content reduced to 1%. It was shown that lowering the oxygen concentration inhibited the activity of derivative These results indicate that oxygen is essential for the activity of this compound and the mechanism of action is most likely related to the generation of singlet oxygen, the formation of which depends on the presence of molecular oxygen[7].…”

“…BODIPY 2 was iodinated to obtain a new derivative 4 or quaternized to give amphiphilic BODIPY 3. This derivative was then subjected to iodination, which increased the obtained BODIPY's 5 lipophilicity [7,8].…”

“…Iodinated derivatives 4 and 5 showed high activity at a low concentration of 0.25 μM, while non-iodinated BODIPYs 2 and 3 required a 10-fold higher concentration. However, for Gram-negative Escherichia coli, high inactivation was obtained only for cationic, iodinated derivative 5 at a concentration of at least 5 μM[7].Log 10 reductions of S. aureus and E. coli treated withBODIPYs 10 >5.3 log 10 >5.4 log 10 >5.3 log 10Results and discussion -In vitro photodynamic anticancer activityBoth iodinated derivatives 4 and 5 showed high photodynamic anticancer activity with IC 50 values of 48.3 nmol and 19.3 nmol, respectively. Due to the best photodynamic activity, derivative 5 was also assessed under hypoxic conditions with an oxygen content reduced to 1%.…”

“…Normalized absorption spectra of BODIPYs 2-5 in methanol.Maximum absorption (λ max ) and molar absorption coefficients (logε) for derivatives 2Results and discussion -emission propertiesThe non-iodinated derivatives 2 and 3 showed high fluorescence efficiency. The introduction of iodine atoms to the structure of derivatives 4 and 5 caused a 30-35-fold reduction in fluorescence efficiency[7]. This phenomenon, called the heavy atom effect, is caused by an increase in the intersystem crossing from the first singlet excited state to the triplet excited state and resulting reduction in fluorescence intensity.…”