In-silico Screening of Selected Apiaceae Plants as Melanogenesis Inhibitors and their Predicted Skin Permeability

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.