New long-wavelength ethanolamino-substituted hypocrellin: photodynamic activity and toxicity to MGC803 cancer cell

Abstract To improve hydrophilicity and photoactivity of the new type of therapeutic agent, hypocrellin, a novel long-wavelength ethanolamino-substituted hypocrellin B (EAHB) was synthesized and its molecular structure was characterized by IR, NMR, MS, and UV–vis spectrometers, and EAHB had strong absorption at the phototherapeutic window (600–900 nm). Illumination of deoxygenated DMSO solution containing EAHB generated a strong electron paramagnetic resonance (EPR) signal, which was assigned to the semiquinone anion radical of EAHB (EAHB − ). Absorption measurements displayed that the absorptive bands at 632 and 565 nm (shoulder) arose from the semiquinone anion radical (EAHB − ) and the absorptive bands at 519 and 450 nm (shoulder) belonged to hydroquinone (EAHBH 2 ), which were formed via the decay of EAHB − in water-contained solution. Superoxide anion radical (O 2 − ) was produced via electron transfer from EAHB − (the precursor) to ground state oxygen. The presence of NADH, a bio-electron donor, significantly enhanced production of EAHB − and O 2 − . Singlet oxygen O 2 ( 1 Δ g ) could be produced via energy transfer from triplet EAHB to ground state oxygen molecules. The quantum yield of O 2 ( 1 Δ g ) and the relative quantum yield of O 2 − of EAHB were 0.15 and 0.76, respectively, with the parent compound hypocrellin B (HB) as the standard. It was inferred that Type I pathway was possibly a major photodynamic mechanism of EAHB. The study on photobiological action of EAHB on MGC803 cancer cells revealed that EAHB kept the same good phototoxic ability as HB but reduced 4 times cytotoxicity than HB, and also its photopotentiation factor increased 4-folds.