Prospective pharmacological effects of psoralen photoxidation products and their cycloadducts with aminothiols: chemoinformatic analysis

Abstract

Psoralens are medicinal photosensitizing furocoumarins which are used in photochemotherapy and photoimmunotherapy of dermatoses. Psoralen photooxidation products may be involved in therapeutic effects, but the possible mechanisms of their action remain unclear. The study was aimed to assess the prospective pharmacological effects and mechanisms of activity for six previously identified ortho–hydroxyformyl-containing psoralen photooxidation products and their cycloadducts with aminothiols, as well as for structurally similar compounds (furocoumaric acid and tucaresol). Chemoinformatic analysis of the prospective pharmacological effects and mechanisms of action of these compounds was performed using the PASS and PharmaExpert software. The predicted pharmacological effects partially confirmed by previous studies highlight the possible involvement of psoralen photooxidation products in the effects of PUVA therapy or photopheresis during the course of dermatoses and proliferative disorders treatment. A broad spectrum of pharmacological effects found for furocoumaric acid and cycloadducts of coumarinic and benzofuranic photoproducts of psoralen with cysteine and homocysteine appoints new directions of research relating to therapeutic use of psoralens.

Twice as Nice: The Duff Formylation of Umbelliferone Revised

“…Furthermore, the prospective neuroprotective activity of the 6-FUmb cycloadducts with biologically abundant aminothiols (cysteine and homocysteine) was predicted using chemoinformatic analysis [24]. It is known that an elevated level and/or accumulation of homocysteine may result in a large number of neurological conditions (e.g., Alzheimer's disease, senile dementia, vascular disorders, nephropathy, etc.)…”

“…Considering the rising trend in the studies of 6-formylumbelliferone (6-FUmb) biological activities [21][22][23][24], its prospective beneficial spectral properties based on the relevance of 6-formyl vs. 8-formyl positioning [4,25], and the routine usage of 8-formylumbelliferone (8-FUmb) as a reference compound for the above-mentioned studies, we found it important to revise the Duff ortho-formylation of unsubstituted umbelliferone (Umb) and re-evaluate the 8-FUmb and 6-FUmb yields in this convenient and cost-effective reaction.…”

pH-Dependent Photoinduced Interconversion of Furocoumaric and Furocoumarinic Acids

“…The Z → E photoisomerization process was monitored by HPLC and spectrophotometry, and E -FCA was obtained in preparatively useful yield. Assuming a wide range of pharmacological effects previously predicted for E -FCA by means of chemoinformatic analysis [ 23 ], the preparative synthesis of E -FCA outlined in this work is particularly valuable.…”

“…Furocoumaric acid [( Z )-3-(6-hydroxybenzofuran-5-yl)acrylic acid; Z -FCA] is an α-pyrone ring-opening (photo)product of psoralen, while furocoumarinic acid [( E )-3-(6-hydroxybenzofuran-5-yl)acrylic acid; E -FCA] is E -isomer of Z -FCA ( Scheme 1 ). Recently, a wide range of pharmacological effects was predicted for E -FCA by means of chemoinformatic analysis [ 23 ]. These effects include a number of protective (i.e., neuro-, vaso-, and radioprotective) effects, antimutagenic, anticarcinogenic, antioxidant, and anti-inflammatory activities, and even a prospective dermatologic (in particular, antipsoriatic) therapeutic activity.…”