- Investigation of the effect of the NH···OC hydrogen bond from Cys69 to PYP chromophore using novel active-center model compound
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A PYP active-center model compound containing a hydrogen bond to the conjugated carbonyl oxygen was synthesized and its effect on the electronic properties of the chromophore were investigated. The intramolecular hydrogen bond induces significant change i
- Okamoto, Kentaro,Hamada, Norio,Sumi, Toshiaki,Okamura, Taka-Aki,Ueyama, Norikazu,Yamamoto, Hitoshi
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- Synthesis of cinnamic amide derivatives and their anti-melanogenic effect in α-MSH-stimulated B16F10 melanoma cells
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Of the three enzymes that regulate the biosynthesis of melanin, tyrosinase and its related proteins TYRP-1 and TYRP-2, tyrosinase is the most important because of its ability to limit the rate of melanin production in melanocytes. For treating skin pigmentation disorders caused by an excess of melanin, the inhibition of tyrosinase enzyme is by far the most established strategy. Cinnamic acid is a safe natural product with an (E)-β-phenyl-α,β-unsaturated carbonyl motif that we have previously shown to play an important role in high tyrosinase inhibition. Since cinnamic acid is relatively hydrophilic, which hinders its absorption on the skin, fifteen less hydrophilic cinnamic amide derivatives (1–15) were designed as safe and more potent tyrosinase inhibitors and were synthesized through a Horner-Wadsworth-Emmons reaction. The use of conc-HCl and acetic acid for debenzylation of the O-benzyl-protected cinnamic amides 40–54 produced the following three results. 1) Cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group, irrespective of the amine type of the amides, produced complex compounds with high polarity. 2) Cinnamic amides 40–42, 44, 50–52, and 54 with a benzylamino, or diethylamino group produced the desired debenzylated cinnamic amides 1–3, 5, 10–13, and 15. 3) Cinnamic amides 45–47, and 49 with an anilino moiety provided 3,4-dihydroquinolinones 16–19 through intramolecular Michael addition of the anilide group. Notably, the use of BBr3 as an alternative debenzylating agent for debenzylation of cinnamic amides 45–49 with the anilino moiety provided our desired cinnamic amides 6–10 without inducing the intramolecular Michael addition. Debenzylation of cinnamic amides 43, 48, and 53 with a 2,4-dibenzyloxyphenyl group was also successfully accomplished using BBr3 to give 4, 9, and 14. Among the nine compounds that inhibited mushroom tyrosinase more potently at 25 μM than kojic acid, four cinnamic amides 4, 5, 9, and 14 showed 3-fold greater tyrosinase inhibitory activity than kojic acid. The docking simulation using tyrosinase indicated that these four cinnamic amides (?6.2 to ?7.9 kcal/mol) bind to the active site of tyrosinase with stronger binding affinity than kojic acid (?5.7 kcal/mol). All four cinnamic amides inhibited melanogenesis and tyrosinase activity more potently than kojic acid in α-MSH-stimulated B16F10 melanoma cells in a dose-dependent manner without cytotoxicity. The strong correlation between tyrosinase activity and melanin content suggests that the anti-melanogenic effect of cinnamic amides is due to tyrosinase inhibitory activity. Considering that the cinnamic amides 4, 9, and 14, which exhibited strong inhibition on mushroom tyrosinase and potent anti-melanogenic effect in B16F10 cells, commonly have a 2,4-dihydroxyphenyl substituent, the 2,4-dihydroxyphenyl substituent appears to be essential for high anti-melanogenesis. These results support the potential of these four cinnamic amides as novel and potent tyrosinase inhibitors for use as therapeutic agents with safe skin-lightening efficiency.
- Ullah, Sultan,Kang, Dongwan,Lee, Sanggwon,Ikram, Muhammad,Park, Chaeun,Park, Yujin,Yoon, Sik,Chun, Pusoon,Moon, Hyung Ryong
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- Green synthesis of isoxazoline derivatives using microwave irradiation and their antifungal activity
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Microwave irradiation method was used for synthesis of isoxazolines. Claisen Schmidt reaction of different aromatic aldehydes with acetanilide gave acrylamides (1a-1h) which on further reaction with hydroxylamine hydrochloride (in the presence of sodium hydroxide) afforded isoxazolines (2a-2h). Physical data of all the synthesized compounds were recorded. Isoxazolines were characterized by their IR and 1H NMR spectra. All the synthesized isoxazolines were screened for their antifungal activity against fungi namely Drechslera maydis and Rhizoctonia solani isolated from maize. Isoxazolines having chloro substitution on benzene ring found to be most effective followed by fluoro and nitro substituted compounds. None of the compound was registered as effective as Bavistin.
- Goyal, Akhil,Sharma, Sunita,Gaba, Jyoti,Kaur, Harleen
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p. 2169 - 2172
(2016/07/19)
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- Synthesis and structure-activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors
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Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure-activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities.
- Shi, Zhi-Hao,Li, Nian-Guang,Shi, Qian-Ping,Tang, Hao,Tang, Yu-Ping,Li, Wei,Yin, Lian,Yang, Jian-Ping,Duan, Jin-Ao
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p. 1206 - 1211
(2013/03/14)
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- Synthesis and structure-activity relationships of substituted cinnamic acids and amide analogues: A new class of herbicides
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In the present investigation, substituted cinnamic acids (3-hydroxy, 4-hydroxy, 2-nitro, 3-nitro, 4-nitro, 3-chloro, and 4-methoxy) and their amide analogues with four different types of substituted anilines have been synthesized. The synthesized compounds have been screened for their germination inhibition activity on radish (Raphanus sativus L. var. Japanese White) seeds at 50, 100, and 200 ppm concentrations, and the activity was compared with standard herbicide, metribuzin formulation (sencor). Significant activity was exhibited by all of the compounds. It was observed that with the increase in concentration of the test solution, the activity also increased. All of the compounds showed more than 70% inhibition at 100 ppm concentration except 4-hydroxy cinnamanilide. The compound, 2-chloro (4′-hydroxy) cinnamanilide was the best among the tested compounds, and it was found to be at par with the standard, metribuzin at all concentrations. Thus, it can be concluded that substituted cinnamic acids and their amide analogues may be developed as potential herbicides.
- Vishnoi, Shipra,Agrawal, Vikash,Kasana, Virendra K.
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experimental part
p. 3261 - 3265
(2010/06/14)
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