Design, synthesis and antitumor study of novel NO-type porphyrin–ferulic acid derivatives for chemotherapy and photodynamic therapy†

Abstract

Photodynamic therapy (PDT) is a minimally invasive treatment that shows promise in replacing traditional surgery, chemotherapy, and radiotherapy. In this study, 15 NO-type porphyrin ferulic acid derivatives were synthesized using acyl chlorination, substitution, and complexation with metal salts. After 10 s of light irradiation, the NO-type porphyrin–ferulic acid derivatives could effectively quench DPBF, among which compounds 6a–6e and compounds 7a–7e reduce the fluorescence intensity of DPBF to below 30, indicating that they have a good ability to produce singlet oxygen. Additionally, NO-type porphyrin–ferulic acid derivatives rapidly released NO in 5 min and substantially increased its level within 60 min. The anti-tumour activity experiments showed that NO porphyrin ferulic acid derivatives could produce different degrees of phototoxicity toward A549 cells and HepG2 cells under light conditions. The compounds with shorter alkyl chains showed better antitumor activity, while the elongation of alkyl chains reduced the activity of the compounds. Among these compounds, compound 7a showed optimal inhibition (IC₅₀ = 43.82 ± 2.50) and had the potential to be a combination therapeutic agent for photodynamic therapy and chemotherapy.