In silico molecular docking of luteolin as a potential antihyperpigmentation agent

Lucienne Agatha Larasati Nugraha Putri; Ni Luh Ari Krisma Anjani; Ni Putu Linda Laksmiani; Ni Made Pitri Susanti

doi:10.51511/pr.61

Lucienne Agatha Larasati Nugraha Putri Department of Pharmacy, Faculty of Mathematics and Natural Science, Udayana University, Bukit Jimbaran, Badung, Bali 80361, Indonesia https://orcid.org/0009-0008-5259-3748
Ni Luh Ari Krisma Anjani Department of Pharmacy, Faculty of Mathematics and Natural Science, Udayana University, Bukit Jimbaran, Badung, Bali 80361, Indonesia
Ni Putu Linda Laksmiani Department of Pharmacy, Faculty of Mathematics and Natural Science, Udayana University, Bukit Jimbaran, Badung, Bali 80361, Indonesia https://orcid.org/0000-0002-5492-7923
Ni Made Pitri Susanti Department of Pharmacy, Faculty of Mathematics and Natural Science, Udayana University, Bukit Jimbaran, Badung, Bali 80361, Indonesia https://orcid.org/0000-0003-4010-1378

Keywords: antihyperpigmentation, hyperpigmentation, luteolin, in silico, molecular docking

Abstract

Excessive melanin synthesis, often triggered by overexposure to UV rays, is catalyzed by melanogenesis enzymes such as tyrosinase, tyrosinase-related protein 1, and D-dopachrome tautomerase. Derived from natural sources, the flavonoid compound luteolin is explored for its antihyperpigmentation potential. This study assesses luteolin’s efficacy as an antihyperpigmentation agent by analyzing its affinity and bond interactions with melanogenesis enzymes through an in silico approach. Molecular docking, facilitated by HyperChem 8 for test compound optimization and Chimera 1.11.1 for protein preparation, alongside method validation and docking with AutoDockTools 1.5.6, established the protocol’s validity with an RMSD value of ≤3 Å. Docking results reveal luteolin's higher affinity for the target proteins compared to native ligands, with binding energies of -5.63 kcal/mol for tyrosinase, -6.18 kcal/mol for tyrosinase-related protein 1, and -6.54 kcal/mol for D-dopachrome tautomerase. The interaction between luteolin and these proteins involves hydrogen, hydrophobic, electrostatic, and Van der Waals bonds, with amino acid residues His61, Lys129, Arg132 (tyrosinase); His192, His224, Val89 (tyrosinase-related protein 1); and Ile64, Asn73 (D-dopachrome tautomerase) participating in hydrogen bond formation. These findings suggest luteolin’s significant potential as an antihyperpigmentation agent by inhibiting melanogenesis enzymes.

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