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

Skarga VV1,2, Zadorozhny AD1, Shilov BV1, Nevezhin EV1, Negrebetsky VV1, Maslov MA2, Lagunin AA1,3, Malakhov MV1
About authors

1 Pirogov Russian National Research Medical University, Moscow, Russia

2 MIREA — Russian Technological University, Moscow, Russia

3 Institute of Biomedical Chemistry (IBMC), Moscow, Russia

Correspondence should be addressed: Vladislav V. Skarga
Ostrovityanova, 1, Moscow, 117437; moc.liamg@dalvagraks

About paper

Funding: the study was supported by RFBR, project number 19-33-90277.

Author contribution: Skarga VV — literature analysis, data analysis and interpretation, manuscript writing and editing; Zadorozhny AD, Shilov BV — data acquisition and analysis; Nevezhin EV — literature analysis, data interpretation; Negrebetsky VV — data interpretation, manuscript writing; Maslov MA — study design; Lagunin AA — study design, literature analysis, manuscript writing; Malakhov MV — study design, literature analysis, data interpretation, manuscript writing and editing.

Received: 2020-08-27 Accepted: 2020-09-22 Published online: 2020-10-10

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.

Keywords: PASS, psoralens, coumarins, benzofurans, aldehydes, furocoumaric acid, aminothiols, (Q)SAR, PharmaExpert