Autophagy induction in TNBC cells by 5,15-diazaporphyrins: synthesis, X-ray structure, ROS generation and photodynamic efficiencies

A series of novel 5,15-diazaporphyrins having N-substitutions in place of C-5 and C-15 atoms were synthesized and characterized. The substitution of N-5 and N-15 atoms in the core led to highly planar diazaporphyrin ring and intense absorption band between 640 and 700 nm. All the diazaporphyrins exhibited strong fluorescence around 640 nm with 4–29 % emission quantum yields. The in-vitro photocytotoxicity studies of diazaporphyrins on triple-negative breast cancer cells revealed excellent autophagy activation. The homoleptic diazaporphyrin displayed excellent IC₅₀ value (1.1 µM) in combination with chloroquine. The diazaporphyrins colocalized in the endoplasmic reticulum and caused stress in cancer cells. One of the diazaporphyrin acted as excellent autophagy inducer and enhanced the expression of autophagy marker proteins as established by western blot analysis. The autophagy inducing 5,15-diazaporphyrins are promising candidates as theragnostic agents for triple negative breast cancer.