Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery
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 psoriasi...
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MDPI AG
2024-01-01
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| author | Natália Andrýsková Jozef Motyčka Melánia Babincová Peter Babinec Mária Šimaljaková |
| author_facet | Natália Andrýsková Jozef Motyčka Melánia Babincová Peter Babinec Mária Šimaljaková |
| author_sort | Natália Andrýsková |
| collection | DOAJ |
| description | 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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| last_indexed | 2024-03-08T04:01:01Z |
| publishDate | 2024-01-01 |
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| series | Applied Sciences |
| spelling | doaj.art-deefdf5405c543e4a9bfa255e6c8847f2024-02-09T15:07:42ZengMDPI AGApplied Sciences2076-34172024-01-01143109410.3390/app14031094Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug DeliveryNatália Andrýsková0Jozef Motyčka1Melánia Babincová2Peter Babinec3Mária Šimaljaková4Department of Dermatovenereology, Faculty of Medicine, Comenius University and Bratislava University Hospital, Mickiewiczova 13, 813 69 Bratislava, SlovakiaDepartment of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University Bratislava, Odbojárov 10, 832 32 Bratislava, SlovakiaDepartment of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynská dolina F1, 842 48 Bratislava, SlovakiaDepartment of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, Mlynská dolina F1, 842 48 Bratislava, SlovakiaDepartment of Dermatovenereology, Faculty of Medicine, Comenius University and Bratislava University Hospital, Mickiewiczova 13, 813 69 Bratislava, SlovakiaPsoriasis 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.https://www.mdpi.com/2076-3417/14/3/1094psoriasisdithranolsalicylic acidester bondprodrugquantum chemistry |
| spellingShingle | Natália Andrýsková Jozef Motyčka Melánia Babincová Peter Babinec Mária Šimaljaková Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery Applied Sciences psoriasis dithranol salicylic acid ester bond prodrug quantum chemistry |
| title | Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery |
| title_full | Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery |
| title_fullStr | Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery |
| title_full_unstemmed | Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery |
| title_short | Computational Design of a Novel Dithranol–Salicylic Acid Antipsoriatic Prodrug for Esterase-Activated Topical Drug Delivery |
| title_sort | computational design of a novel dithranol salicylic acid antipsoriatic prodrug for esterase activated topical drug delivery |
| topic | psoriasis dithranol salicylic acid ester bond prodrug quantum chemistry |
| url | https://www.mdpi.com/2076-3417/14/3/1094 |
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