Effects of α-tocopherol on phototoxicity of 8 - methoxypsoralene

Effects of singlet oxygen extinguisher α-tocopherol on combined effects of psoralens and UV on erythema photosensitized with 8-methoxypsoralene were investigated. The leading role of the reactions of photocompounds in induction of PUVA - erythema is considered. A characteristic feature of biologically active psoralens is the high value of quantum output of intercombination conversion, due to which, after absorption of light quants, a significant number of psoralen molecules are formed in a triplet excited state. Psoralen derivatives differ greatly in their ability to photosensitize the skin. In the example of 8-psoralens, a correlation was found between the ability to induce erythema by photocompound to double-spiral DNA in vitro. A clear correlation was identified between the ability to photosensitize erythema and form diadducts. Α-tocopherol has been shown to protect the skin from PUVA erythema if presents during irradiation. In the case of application of α-tocopherol after irradiation, the inhibitory effect was not exhibited.

Photodynamic Therapy (PDT): An Alternative Approach for Combating COVID-19

The COVID-19 disease initially originated in Wuhan (China) and then spread worldwide has been declared a pandemic by the World Health Organization (WHO). Many attempts are ongoing to find an effective therapeutic treatment and vaccine to cure or prevent the disease, but the success is very little. Even some of the approved vaccines are also disputed for safety issues. This is the time where we should think of alternative treatments to control the disease effectively. Photodynamic therapy (PDT) is a technique that is widely used in cancer treatment and against various microbes. In this technique, a light-induced photosensitizer generates reactive oxygen species (ROS), ultimately killing the target cells. Considering these facts, an attempt has been made to review the current literature on viral inactivation using PDT approach. Accordingly, the mechanism of PDT action has been discussed, along with an update on the use of various photosensitizers (PSs) and nanoparticles. The capsid proteins and nucleic acid (RNA) of SARS-CoV-2 can be a possible target for PDT. To understand this interaction further, computational modeling studies have been discussed to help design effective PSs. Overall, the PDT technique has therapeutic potential and should be tested as a complementary or alternative treatment for control of COVID-19 using the PSs like curcumin, psoralen derivatives, riboflavin, etc. This review discusses COVID-19, its outbreak, diagnosis, the existing treatment modalities, and how PDT can be an effective alternative treatment for controlling the disease.

Psoralen Derivatives: Recent Advances of Synthetic Strategy and Pharmacological Properties

Psoralen or furocoumarin is a linear three ring heterocyclic compound. Psoralens are planar, tricyclic compounds, consisting of a furan ring fused to a coumarin moiety. Psoralen has been known for a wide spectrum of biological activities, spanning from cytotoxic, photosensitizing, insecticidal, antibacterial to antifungal effect. Thus, several structural changes were introduced to explore the role of specific positions with respect to the biological activity. Convenient approaches utilized for the synthesis of psoralen skeleton can be categorized into two parts: (i) the preparation of the tricyclic ring system from resorcinol, (ii) the exocyclic modification of the intact ring system. Furthermore, although psoralens have been used in diverse ways, we mainly focus in this work on their clinical utility for the treatment of psioraisis, vitiligo and skin-related disorder.

Psoralen Derivatives as Inhibitors of Mycobacterium tuberculosis Proteasome

Protein degradation is a fundamental process in all living organisms. An important part of this system is a multisubunit, barrel-shaped protease complex called the proteasome. This enzyme is directly responsible for the proteolysis of ubiquitin- or pup-tagged proteins to smaller peptides. In this study, we present a series of 92 psoralen derivatives, of which 15 displayed inhibitory potency against the Mycobacterium tuberculosis proteasome in low micromolar concentrations. The best inhibitors, i.e., 8, 11, 13 and 15, exhibited a mixed type of inhibition and overall good inhibitory potency in biochemical assays. N-(cyanomethyl)acetamide 8 (Ki = 5.6 µM) and carboxaldehyde-based derivative 15 (Ki = 14.9 µM) were shown to be reversible inhibitors of the enzyme. On the other hand, pyrrolidine-2,5-dione esters 11 and 13 irreversibly inhibited the enzyme with Ki values of 4.2 µM and 1.1 µM, respectively. In addition, we showed that an established immunoproteasome inhibitor, PR-957, is a noncompetitive irreversible inhibitor of the mycobacterial proteasome (Ki = 5.2 ± 1.9 µM, kinact/Ki = 96 ± 41 M−1·s−1). These compounds represent interesting hit compounds for further optimization in the development of new drugs for the treatment of tuberculosis.