Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery
Source abstract
Abstract
Psoriasis is a chronic autoimmune skin disorder characterized by the rapid overproduction of skin cells, resulting in the formation of red, inflamed, and scaly patches or plaques on the skin. Dithranol, also known as anthralin, is a very effective topical medication used in the treatment of psoriasis, with several shortcomings like photo-instability; staining skin, clothing, and bedding; and causing skin irritation. Antiproliferative dithranol is frequently used in combination therapy with keratolytic salicylic acid. We have therefore proposed a novel topical antipsoriatic prodrug comprising dithranol and salicylic acid joined together with an ester bond, specifically 8-hydroxy-9-oxo-9,10-dihydroanthracen-1-yl-2-hydroxybenzoate. An ester bond is cleavable by endogenous esterase hydrolyzing this bond and releasing dithranol and salicylic acid in a 1:1 stoichiometric ratio. We performed an exhaustive theoretical analysis of this molecule using the reliable computational methods of quantum chemistry and ADME in silico studies to investigate its biological and pharmacokinetic activities. We found its molecular structure, vibrational spectra, molecular orbitals, MEP (molecular electric potential), UV-VIS spectra, and TDOS (total density of states), and we performed an RDG (reduced density gradient) analysis. The obtained results may be useful for the understanding of its properties, which may assist in the synthesis and further experimental study of this possible antipsoriatic dual-action prodrug with reduced adverse effects and enhanced therapeutic efficacy.
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Research context
OpenAlex topics: Essential Oils and Antimicrobial Activity · Psoriasis: Treatment and Pathogenesis · Synthesis and biological activity
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Dermatovenereology, Faculty of Medicine, Comenius University and Bratislava University Hospital, Mickiewiczova 13, 813 69 Bratislava, Slovakia
Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 832 32 Bratislava, Slovakia
Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynská dolina F1, 842 48 Bratislava, Slovakia
Funding
Slovak Grant Agency VEGA
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