scholarly journals Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Yasir Nazir ◽  
Hummera Rafique ◽  
Sadia Roshan ◽  
Shazia Shamas ◽  
Zaman Ashraf ◽  
...  

Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002   μ M , while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6   μ M in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5   μ M and IC50 of 16.69 ± 2.8   μ M , respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 μM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2477
Author(s):  
Yasir Nazir ◽  
Hummera Rafique ◽  
Naghmana Kausar ◽  
Qamar Abbas ◽  
Zaman Ashraf ◽  
...  

Targeting tyrosinase for melanogenesis disorders is an established strategy. Hydroxyl-substituted benzoic and cinnamic acid scaffolds were incorporated into new chemotypes that displayed in vitro inhibitory effects against mushroom and human tyrosinase for the purpose of identifying anti-melanogenic ingredients. The most active compound 2-((4-methoxyphenethyl)amino)-2-oxoethyl (E)-3-(2,4-dihydroxyphenyl) acrylate (Ph9), inhibited mushroom tyrosinase with an IC50 of 0.059 nM, while 2-((4-methoxyphenethyl)amino)-2-oxoethyl cinnamate (Ph6) had an IC50 of 2.1 nM compared to the positive control, kojic acid IC50 16700 nM. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound (Ph9) and Ph6 exhibited 94.6% and 92.2% inhibitory activity respectively while the positive control kojic acid showed 72.9% inhibition. Enzyme kinetics reflected a mixed type of inhibition for inhibitor Ph9 (Ki 0.093 nM) and non-competitive inhibition for Ph6 (Ki 2.3 nM) revealed from Lineweaver–Burk plots. In silico docking studies with mushroom tyrosinase (PDB ID:2Y9X) predicted possible binding modes in the catalytic site for these active compounds. Ph9 displayed no PAINS (pan-assay interference compounds) alerts. Our results showed that compound Ph9 is a potential candidate for further development of tyrosinase inhibitors.


2019 ◽  
Vol 17 (1) ◽  
pp. 3-11
Author(s):  
Ioannis Fotopoulos ◽  
Eleni Pontiki ◽  
Dimitra Hadjipavlou Litina

Background: Cinnamic acid is a key intermediate in shikimate and phenylpropanoid pathways. It is found both in free form, and especially in the form of esters in various essential oils, resins and balsams which are very important intermediates in the biosynthetic pathway of several natural products. The cinnamic derivatives play a vital role in the formation of commercially important intermediate molecules which are necessary for the production of different bioactive compounds and drugs. Different substitutions on basic moiety lead to various biological activities. Furthermore, combination of appropriate pharmacophore groups with cinnamic acid derivatives were developed to give hybrids in order to find out promising drug candidates as inhibitors of multiple biological targets associated with inflammation. We found interesting to continue our efforts to design and synthesise three series of novel cinnamic acid-based hybrids: a) nitrooxy esters of cinnamic acid, b) ethers and c) amides of cinnamic acids with arginine, as pleiotropic candidates against multiple targets of inflammation. Methods: The synthesis of cinnamic was established by a Knoevenagel-Doebner condensation of the suitable aldehyde either with malonic acid in the presence of pyridine and piperidine, or with phenylacetic acid in the precence of triethylamine in acetic anhydride. The synthesis of the corresponding esters was conducted in two steps. The ethers were synthesized in low yields, with 1,2 – dibromoethane in dry acetone, in the presence of K2CO3, to give oily products. The corresponding cinnamic amides were synthesised in a single step. The synthesised hybrids were tested as lipoxygenase (LOX) and cyclooxygenase (COX) inhibitors in vitro. In silico docking was applied to all the novel derivatives. Several molecular properties of the hybrids were calculated in order to evaluate their drug likeness. Results: A number of esters, ethers and amides of selected cinnamic acids, either phenyl substituted or not, has been synthesised and subjected to modelling studies. The compounds were studied in vitro/in vivo for their inhibitory activities on cox and lox, and as antioxidants. Log P values of all the title compounds except of 3a (5.38) were found to be less than 5 and are in agreement to Lipinski’s rule of five, suggesting satisfactory permeability across cell membrane. The molecular modelling study seems to be in accordance with the experimental results for LOX and COX-2. The result of antioxidant activity for amide 3b supports the anti-lox activity. Compound 5d presents the higher in vivo anti-inflammatory. Conclusion: According to the experimental findings compounds 3b and 5d can be used as lead compounds for the design of new molecules to target inflammation.


2012 ◽  
Vol 48 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Raquel da Silva Teixeira ◽  
Paula Rafaela Rocha ◽  
Hudson Caetano Polonini ◽  
Marcos Antônio Fernandes Brandão ◽  
Maria das Graças Afonso Miranda Chaves ◽  
...  

In order to treat hyperpigmentation-related problems, there has been a global trend in developing cosmetics claiming to have skin-whitening properties, which act by inhibiting melanin biosynthesis. The objective of this work was to evaluate the in vitro mushroom tyrosinase inhibitory activity of five Amazonian native flora oils, and so to verify the possibility of their incorporation into cosmetic products. In addition, the fatty acid composition of the essential oils was determined by gas chromatography-flame ionisation detection in order to determine the main components of these oils. The tyrosinase inhibitory activity of the tested oils was found to be in the following order: açaí (IA50 = 66.08 µg mL-1) > tucumã > patauá > pracaxi > castanha do Brasil. This study suggests that açaí oil has great potential in the treatment of hyperpigmentation and other related disorders, due to its considerable tyrosinase inhibitory activity.


2014 ◽  
Vol 71 (1) ◽  
Author(s):  
Shajarahtunnur Jamil ◽  
Siti Awanis Abdullah ◽  
Siti Mariam Abdul Lathiff ◽  
Hasnah Mohd Sirat

Tyrosinase inhibitory activity was studied on the crude extracts and flavonoids successfully isolated from the leaves and heartwoods of Artocarpus lowii King. The flavonoids were fully characterized spectroscopically as isobavachalcone (1), 4-hydroxyonchocarpin (2), 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone (3), 2',4'-dihydroxy-3,4-(2",2"-dimethylchromeno)-3'-prenyldihydrochalcone (4), artocarpin (5), cycloheterophyllin (6) and 4',5-dihydroxy-6,7-(2,2-dimethylpyrano)-2'-methoxy-8-γ,γ-dimethyl allylflavone (7). Tyrosinase inhibitory activity of the samples was determined against mushroom tyrosinase using ELISA microplate reader. Cycloheterophyllin (6) exhibited an excellent inhibitory activity against mushroom tyrosinase comparable to the standard kojic acid with the IC50 value of 52.5 µg/mL (88.3%).


Author(s):  
MUTHUSWAMY UMAMAHESWARI ◽  
Preetha Prabhu ◽  
KUPPUSAMY ASOKKUMAR ◽  
THIRUMALAISAMY SIVASHANMUGAM ◽  
Varadharajan Subhadradevi ◽  
...  

2016 ◽  
Vol 16 (1) ◽  
pp. 18 ◽  
Author(s):  
Vidyalakshmi Subramanian ◽  
Dhamodharan Sahithya

Tyrosinase inhibition is an important approach towards controlling hyper pigmentation. We aimed to screen alcoholic extracts of 11 plants extract for their tyrosinase inhibitory activity. These plants have been used traditionally in the treatment of skin ailments and for the improvement of skin complexion. The extracts were quantified for total phenols, alkaloids and tannins. <em>In vitro</em> tyrosinase inhibition was performed with kojic acid as the positive control. Cell viability was tested on B16 F0 melanoma cells. The extracts of <em>Rosa berberifolia</em>, <em>Punica granatum</em> and <em>Casiia angustifolia</em> showed more than 80% inhibition at 500 mg/ml concentration. Nine of the extracts were also shown to have a high phenolic content greater than 200 mg/g of the plant material. The tyrosinase inhibitory activity of the extracts of <em>Cassia angustifolia, Punica granatum </em>and<em> Rosa berberifolia</em> were comparable with that of the control, kojic acid. The three extracts also showed lesser than 50% cytotoxicity at the concentrations tested. From the screening assays, it is seen that three plants have appreciable tyrosinase inhibitory activity. Hence, these plants may be further evaluated for their use in cosmetics and hyper pigmentation.


2008 ◽  
Author(s):  
Yovani Marrero-Ponce ◽  
Gerardo Casañola-Martín ◽  
Mahmud Khan ◽  
Arjumand Ather ◽  
Kalid Khan ◽  
...  

Talanta ◽  
2012 ◽  
Vol 101 ◽  
pp. 233-239 ◽  
Author(s):  
Nuntaporn Moonrungsee ◽  
Tomoko Shimamura ◽  
Takehiro Kashiwagi ◽  
Jaroon Jakmunee ◽  
Keiro Higuchi ◽  
...  

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