Development of novel porphyrin/combretastatin A-4 conjugates for bimodal chemo and photodynamic therapy: Synthesis, photophysical and TDDFT computational studies

Anticancer photodynamic therapy (PDT) in recent years has gained attention among therapists due to its low systemic toxicity and non-invasive nature. Today, one of the big trends in the development of photosensitizers for photodynamic therapy is a construction of advanced multifunctional molecules, which can overcome known problems for conventional drugs. In this paper, we made an attempt to create bimodal conjugates consisting of a meso-tetraphenylporphyrin (photosensitizer) and E-combretastatin A-4 (chemotherapeutic drug), which under light irradiation could: 1) participate in photodynamic treatment by ROS generation; 2) participate in chemotherapy by liberation of low-toxic E-combretastatin A-4 followed by its photoisomerization into more cytotoxic Z-combretastatin A-4. We believe, that such conjugates should demonstrate a low dark toxicity and significant light-induced antitumor properties due to step-by-step transformation of E-combretastatin A-4 into Z-combretastatin A-4. Thus, we describe the design, synthesis, photophysical and TDDFT computational studies for the new class of porphyrin/combretastatin A-4 conjugates.