Chemists obtaine and explore compounds for possible photodynamic antitumor therapy

A group of scientists from INEOS RAS synthesized a series of β-maleimide substituted porphyrins for cancer treatment by the light. Their biological activity was explored by Albina Petrova, a biochemist, RUDN staff member. New porphyrins were found to generate new forms of oxygen when radiating tumor cells via monochromatic light, which could make them effective compounds for antitumour photodynamic therapy. The results were published in the journal Dyes and Pigments.

In cancer treatment, much is anticipated from photodynamic therapy, an approach based on the generation of active forms of oxygen in tumor cells by light radiation. This approach implies the use of fotosensibilisators, compounds that make tissues more sensitive to light by radiation. However, low quantum efficiency, toxicity and poor accumulation in tissues limit a large number of fotosensibilisators, inhibiting their usage. A search for new fotosensibilisators to become medicine agents for photodynamic therapy, is required.

The article authors obtained a new series of β-Maleimide substituted meso-arylporphyrins. The important advantage of Maleimide substitute is the ability to react selectively with thiol groups of cysteine in proteins, which is a useful strategy for regioselective delivery of photosensitisers to targeting cells. β-Maleimide substitutes of porphyrins have been derived by the interaction of porphyrins β-amino group with maleic anhydride followed by cyclization of forming amids of maleic acid. The authors also explored fixation of the maleimide group of porphyrins with cysteine as a model reaction. A series of boronated porphyrins with mercapto carboranes to be used in tumor photodynamics and boron neutron capture therapy was obtained. Fixation with albumin, the main medicine transporter in a body, optical properties, such as fluorescence and its quantum efficiency. Experiments in vitro on the tumor cells were also conducted.

The researchers found that the derived compounds' quantum efficiency of single oxygen reaches more than 70%. Albina Petrova found that the best results were shown by boronated derivative {3-[(о-carboranyl-1'-yl)thio]pirrolidine-2,5-dione-1-yl}-5,10,15,20-tetraphenylporphyrin. This compound didn't appear toxic towards tumor cells in the dark, but when radiating by the light the generalization of active forms of oxygen appeared in the first minutes. This process brought to intercellulary membrane destruction and quick death of tumor cells by the necrosis mechanism.

The authors came to the conclusion that β-maleimide battered porphyrins and meso-aryl porphyrins and their boron derivatives are the perspective compounds for photodynamic and Boron neutron capture therapy, as well as for deep exploration as multifunctional biologically active substances.

Photoactive compounds may be used for antimicrobial therapy. Pathogenic bacterium form associates where they cooperate (biofilms). "Antibiotics' activity is week in these associations. But if bacterium are loaded by porphyrins and exposed to light, an explosion will cause microbes' death. These actions help to treat wound infection and clear urethral and gallstones", noticed Albina Petrova.

More information:
Valentina A. Ol'shevskaya et al. β-Maleimide substituted meso-arylporphyrins: Synthesis, transformations, physico-chemical and antitumor properties, Dyes and Pigments (2019). DOI: 10.1016/j.dyepig.2019.107760

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