Curcumin-Based Tyrosinase-Targeting Derivatives for Cell Imaging and Depigmenting Effect
- 1Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale F. Stagno d’Alcontres 31, 98166 Messina, Italy
- 2Proteomics and Tumor Biochemistry Group, Department of Experimental and Clinical Medicine, School of Medicine, Magna Græcia University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
- 3Fondazione “Prof. Antonio Imbesi”, 98123 Messina, Italy
Abstract
Targeting melanogenesis through tyrosinase inhibition represents a key therapeutic strategy, highlighting the need for novel molecules capable of modulating melanin synthesis and/or serving as fluorescent probes for cellular and melanoma tracking. In this study, two curcumin (CUR) derivatives, CUR-C3-PP 1 and CUR-CO-PP 2, were designed and successfully synthesized by strategic integration of a 4-(piperazin-1-yl)phenol pharmacophore into CUR skeleton. In vitro enzymatic assays against Agaricus bisporus tyrosinase (AbTYR) revealed that derivatives CUR-C3-PP 1 and CUR-CO-PP 2 amplified the diphenolase inhibitory capacity (IC50 values of 51.20 μM and 12.89 μM, respectively) when compared to parent curcumin (IC50 = 168.57 μM). Notably, CUR-CO-PP 2 emerged as the most potent candidate, significantly eclipsing native CUR and outperforming the standard inhibitor kojic acid (KA). Enzyme kinetics and molecular docking simulations rationalized this enhanced profile, and the mechanism of inhibitory effects for compounds CUR-C3-PP 1 and CUR-CO-PP 2. Cellular assays highlighted that CUR-C3-PP 1 retained functional intrinsic luminescence, displaying selective accumulation and intense fluorescence within the cytoplasm of B16-F10 melanoma cells alongside preferential cytotoxicity. Screening in zebrafish (Danio rerio) embryos confirmed that both derivatives maintain an excellent biocompatibility profile up to 20 μM. In vivo, both compounds elicited robust, dose-dependent depigmentation, with CUR-CO-PP 2 closely approaching the efficacy of the control 1-phenyl-2-thiourea (PTU). Collectively, our findings demonstrate that the imaging and anti-melanogenic properties of curcuminoids can be independently optimized through rational linker modification, establishing CUR-C3-PP 1 as a promising fluorescent tracer for imaging and CUR-CO-PP 2 as a candidate for depigmenting therapies.
Related
- Synergistic nanotheranostic platform for fluorescence/magnetic resonance bimodal imaging-guided near infrared photoimmuno-chemodynamic thermal targeting therapy.
- New depsidones from Garcinia parvifolia and their antidiabetic, anti-tyrosinase, and antioxidant activities.
- Eicosa-11Z,14Z,17Z-Trienoic Acid Suppresses Melanogenesis by Inhibiting Intracellular MITF/Tyrosinase Axis.
- Novel pathway for curcumin utilization found in diverse Gram-negative soil-dwelling bacteria with evidence of horizontal gene transfer
- Mechanistic Investigation of Cryptotanshinone and Curcumin Combination in Attenuating BVDV-1-Induced Injury in Bovine Ovarian Granulosa Cells.
BibTeX
@article{monforte2026curcuminbased,
title = {{Curcumin-Based Tyrosinase-Targeting Derivatives for Cell Imaging and Depigmenting Effect}},
author = {Maura Monforte and Marilena Pontoriero and Paola Maria Bonaccorsi and Antonella Calderaro and Leonardo Centorrino and Valeria D’Angelo and Laura De Luca and Maria Paola Germanò and Rosaria Gitto and Salvatore Mirabile and Giuseppe Tancredi Patanè and Stefano Putaggio and Domenica Scumaci and Chiara Maria Antonietta Gangemi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198759},
url = {https://www.mdpi.com/1422-0067/27/19/8759},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Curcumin-Based Tyrosinase-Targeting Derivatives for Cell Imaging and Depigmenting Effect
AU - Maura Monforte
AU - Marilena Pontoriero
AU - Paola Maria Bonaccorsi
AU - Antonella Calderaro
AU - Leonardo Centorrino
AU - Valeria D’Angelo
AU - Laura De Luca
AU - Maria Paola Germanò
AU - Rosaria Gitto
AU - Salvatore Mirabile
AU - Giuseppe Tancredi Patanè
AU - Stefano Putaggio
AU - Domenica Scumaci
AU - Chiara Maria Antonietta Gangemi
PY - 2026
DA - 2026/09/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198759
UR - https://www.mdpi.com/1422-0067/27/19/8759
AB - Targeting melanogenesis through tyrosinase inhibition represents a key therapeutic strategy, highlighting the need for novel molecules capable of modulating melanin synthesis and/or serving as fluorescent probes for cellular and melanoma tracking. In this study, two curcumin (CUR) derivatives, CUR-C3-PP 1 and CUR-CO-PP 2, were designed and successfully synthesized by strategic integration of a 4-(piperazin-1-yl)phenol pharmacophore into CUR skeleton. In vitro enzymatic assays against Agaricus bisporus tyrosinase (AbTYR) revealed that derivatives CUR-C3-PP 1 and CUR-CO-PP 2 amplified the diphenolase inhibitory capacity (IC50 values of 51.20 μM and 12.89 μM, respectively) when compared to parent curcumin (IC50 = 168.57 μM). Notably, CUR-CO-PP 2 emerged as the most potent candidate, significantly eclipsing native CUR and outperforming the standard inhibitor kojic acid (KA). Enzyme kinetics and molecular docking simulations rationalized this enhanced profile, and the mechanism of inhibitory effects for compounds CUR-C3-PP 1 and CUR-CO-PP 2. Cellular assays highlighted that CUR-C3-PP 1 retained functional intrinsic luminescence, displaying selective accumulation and intense fluorescence within the cytoplasm of B16-F10 melanoma cells alongside preferential cytotoxicity. Screening in zebrafish (Danio rerio) embryos confirmed that both derivatives maintain an excellent biocompatibility profile up to 20 μM. In vivo, both compounds elicited robust, dose-dependent depigmentation, with CUR-CO-PP 2 closely approaching the efficacy of the control 1-phenyl-2-thiourea (PTU). Collectively, our findings demonstrate that the imaging and anti-melanogenic properties of curcuminoids can be independently optimized through rational linker modification, establishing CUR-C3-PP 1 as a promising fluorescent tracer for imaging and CUR-CO-PP 2 as a candidate for depigmenting therapies.
SN - 1422-0067
ER -