Structural Optimization Of Cannabidiol As Multifunctional Cosmetic Raw Materials

Cannabidiol(CBD)is a secondary metabolite derived from the Cannabis sativa that possesses an array of biological characteristics,including immune response regulation and depression treatment.CBD is also employed in the cosmetics industry due to its antioxidant,anti-inflammatory,anti-wrinkle,and whitening effects.Nevertheless,its primary source,hemp extract,is subject to stringent regulations,thus prompting the search for cannabidiol derivatives with enhanced skin care benefits through structural optimization.In this study,computer-aided molecular design was coupled with experimental techniques to identify novel CBD derivatives with higher biological potency.The first chapter of this paper comprises five sections.The first section expounds on the exogenous factors and underlying mechanisms of oxidative stress,inflammatory response,wrinkle formation,and melanin precipitation in the skin.The second section discusses common treatments for skin problems,while the third section examines natural products that can be used to alleviate these issues.The fourth section focuses on the diverse skin care benefits of cannabidiol.Finally,the fifth section introduces cannabinoid receptor 1.The second chapter of this paper describes the investigation of the mode of action between cannabidiol(CBD)and its target protein,cannabidiol receptor 1(CB1),with the aim of identifying the key molecular skeleton.This skeleton was then used to virtually screen a large database of natural products with a similarity threshold of 70%.Subsequently,the ability of these compounds to bind to the cannabinoid receptor 1 was assessed using Discovery Studio’s CDOCKER module and Schr(?)dinger’s Glide module.The drug-likeness of the identified compounds was evaluated using the Lipinski and Veber rules.Cannabidiol derivatives that exhibited high similarity,phenolic hydroxyl structures,and favorable scoring values were selected based on the gradient of these screening criteria.In the third chapter of this paper,the target compounds were evaluated for their ability to scavenge extracellular ABTS radicals,DPPH radicals,and intracellular reactive oxygen species.Compounds with higher antioxidant capacity than cannabidiol were identified and selected for subsequent efficacy experiments.The fourth chapter of this paper focuses on the anti-inflammatory abilities of compounds exhibiting superior antioxidant capacity to cannabidiol.Specifically,the effects of these compounds on nitric oxide(NO),interleukin 6(IL-6),COX-2 protein,and iNOS protein expression levels in the RAW264.7 cell line were analyzed.Furthermore,the anti-wrinkle ability of these compounds was evaluated by examining the extracellular matrix and apoptosis rates of HFF-1 fibroblasts,including collagen,elastin,and fibrin.The impact of cannabidiol derivatives on melanin content and tyrosinase activity was also assessed.The virtual screening results showed that four cannabidiol derivatives(S-88614,S-88745,S-92151,S-92153)had excellent binding ability,phenolic hydroxyl structure,and high drug-likeness.Extracellular ABTS and DPPH radical scavenging experiments showed that S-88745 and S-92153 had stronger antioxidant capacity than cannabidiol.The experimental results of intracellular reactive oxygen species clearance experiment once again proved that S-88745 and S-92153 have excellent antioxidant capacity.Conopunds S-88745 and S-92153 can inhibit the expression of nitric oxide(NO),interleukin 6(IL-6),COX-2 protein and iNOS protein,and the anti-inflammatory abilities were sorted as S-92153>S-88745>cannabidiol;The results of anti-wrinkle experiments showed that S-88745 and S-92153 could alleviate cell damage caused by ultraviolet rays and promote the expression of collagen,elastin and fibronectin,among which the anti-wrinkle ability of S-92153 was higher than that of cannabidiol.In terms of whitening ability evaluation experiments,S-88745 and S-92153 could inhibit the production of melanin by B16F10 melanoma cells and significantly reduce the activity of intracellular tyrosinase in B16F10 melanoma cells,among which the whitening ability of S-92153 was higher than that of cannabidiol.And the MTT experiments of RAW264.7 and HFF-1 cells showed that cannabidiol was cytotoxic at high concentrations(20～100 μM),and cannabidiol had a killing effect on B16F10 cells from0.128 μM.S-88745 and S-92153 do not kill cells even at high concentrations.Consequently,our investigation yielded S-92153,which demonstrated superior antioxidant,anti-inflammatory,anti-wrinkle,whitening,and cytotoxic properties compared to cannabidiol.Similarly,S-88745,which exhibited comparable anti-wrinkle and skin whitening efficacy as cannabidiol,surpassed cannabidiol in antioxidant capacity,anti-inflammatory activity,and cytotoxicity.These findings suggest that S-88745 and S-92153 hold potential as multifunctional cosmetic ingredients that can replace cannabidiol.