Abstract
Tyrosinase-related protein 1 (TYRP1) is a member of tyrosinase enzyme family which is metal-containing glycoproteins localized in melanosomes where the melanin biosynthesis occurs. The downregulation of tyrosinase is the most protruding approach for the development of skin whitening and depigmentation agents, however, TYRP1 downregulation is considered a novel target for melanogenesis inhibition and is still under clinical investigations for treatment of malignant melanoma. In the present study, virtual screening using glide extra-precision docking of an in-house generated data base of 400 natural compounds belonging to family Apiaceae for TYRP1 inhibitors was performed for the first time. luteolin-7-apiosylglucoside from celery followed by 4-(beta-D-glucopyranosyloxy)benzoic acid then caffeoylquininc acid from anise showed highly potent melanogenesis inhibition even more than the synthetic standard inhibitors such as azelaic and kojic acids. These natural inhibitors exhibited good predicted skin permeability after processing with Qikprop module. Although they had slow predicted transdermal penetration rates, but these rates can be enhanced through optimizing their topical pharmaceutical formulations.
Highlights
Melanogenesis is a process of synthesis of melanin, which is responsible for human skin, eye and hair pigmentation
Plant species belonging to family Apiaceae have recently been established to biosynthesize prenyloxycoumarins; a wide series of oxyprenylated secondary metabolites, in particular umbelliferone derivatives (Taddeo et al, 2017)
We selected four Apiaceae species; Apium graveolens, P Pimpinella anisum, Ammi visnaga and Ammi majus for in-silico screening for novel phytoconstituents with tyrosinaserelated protein 1 (TYRP1) inhibitory activity
Summary
Melanogenesis is a process of synthesis of melanin, which is responsible for human skin, eye and hair pigmentation. Arbutin in its natural forms is unstable and can release hydroquinone which is metabolized to benzene with the prospective bone marrow toxicity (Zhou et al, 2009) For these reasons, a great interest in recent years to find natural, safer and effective alternatives for synthetic depigmenting agents has been evolved (Gholamhoseinian and Razmi, 2012). Insilico screening utilizing computational speed, being fast and cost-effective, possesses great advantages in analyzing large number of compounds for discovering new drugs with good pharmacokinetic potential (Shen et al, 2003) Few coumarins such as esculetin and umbelliferone have been proved to possess strong TYR inhibitory activity (Masamoto et al, 2004)(Ashraf et al, 2015). The virtual activity and predicted skin permeability of the top natural compounds were compared for the first time to that of the standard synthetic skin depigmenting agents aiming at discovering novel, effective and safe melanogenesis inhibitors
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