Repurposing of FDA-approved Drugs as New Treatment for Skin Inflammatory Diseases Targeting TNF-α and IL-1α

Mohd Rusli, Siti Syahnaz (2022) Repurposing of FDA-approved Drugs as New Treatment for Skin Inflammatory Diseases Targeting TNF-α and IL-1α. [Project Paper] (Submitted)

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Abstract

Frequent use of topical corticosteroid as the primary treatment in skin inflammatory diseases remained insufficient due to relapse and regression in most of the treatment as well as the adverse effect on systemic level. TNF-α and IL-1α are examples of inflammatory cytokines that play important role as therapeutic targets for skin inflammatory conditions. Objective: In silico technique approaches were implemented to identify alternative treatment for skin inflammatory diseases via drug repurposing of existing FDA-approved drugs by targeting the TNF-α and IL-1α. Methodology: A total of 29 drugs that are frequently prescribed for treatment of skin diseases was chosen and classified into two different groups which are biologic and non-biologic drugs. A pharmacophore model for both drug groups was constructed via LigandScout 4.4.7. Next, a database of FDA-approved drugs obtained from DrugBank was subjected to virtual screening employing the previously constructed pharmacophore model and LigandScout 4.4.7 to yield possible hit compounds as drug candidates. Subsequently, molecular docking analysis using AutoDock Vina tool of the hit compounds against TNF-α and IL-1α was performed to determine the binding affinity of each hit compound with the proteins. Results: Docking results showed that the top binding affinity scores were exhibited by sulfasalazine and meclocycline to both TNF-α (at -8.3 kcal/mol and -7.6 kcal/mol respectively) and IL-1α (at -8.1 kcal/mol and -7.1 kcal/mol respectively). A number of strong, moderate and weak hydrogen bindings, hydrophobic interactions and pi-pi stacking were identified between the drugs and the proteins by using the visualizers. Discussion: Sulfasalazine and meclocycline expressed high pharmacophore fit scores which resulted in high binding affinity scores for docking analysis. These two compounds exhibited similar pharmacophore features as well as the immunological targets with the common skin inflammatory drugs that can target TNF-α and IL-1α. Conclusion: The study highlights the potential of in silico drug repurposing techniques to produce FDA-approved drug candidates as alternative treatment for skin inflammatory diseases.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	22 Aug 2023 06:49
Last Modified:	22 Aug 2023 06:49
URI:	http://psaspb.upm.edu.my/id/eprint/1403

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