Synthesis and In Situ Studies of New Porphyrin–Curcumin Analog Conjugates for Photodynamic Cancer Therapy

Photodynamic therapy (PDT) has attracted significant attention as an alternative approach to traditional cancer therapies such as radiotherapy, chemotherapy, and surgery. In this work, the synthesis and photophysical properties of conjugates ( 1 – 4 ) of tetraphenylporphyrin and curcumin analogs were prepared and studied as candidates for PDT. The porphyrin components were shown to have fluorescence quantum yields (Φ FL ) in the 0.12–0.15 range, singlet oxygen quantum yields (Φ ∆ ) of 0.33–0.66, and reasonable solubilities in a 1:9 solution of DMSO/water. All four compounds were tested against pancreatic ductal adenocarcinoma (PDAC, AsPC‐1) and lung cancer (A549) cell lines using resazurin assays and FACS and flow cytometry analysis and exhibited little to no dark cytotoxicity (cellular viabilities ranging from 90% to 100%), whereas high cytotoxicity was observed upon irradiation at 640 nm (ranging from 58% to 67% for AsPC‐1 and 54%–69% for A549). Fluorescence imaging indicated significant uptake of 1 – 4 in the mitochondria. The significant cytotoxicity of 1 – 4 is therefore attributed to their accumulation in tumor cells followed by singlet oxygen generation leading to cell death.