3158-56-3Relevant academic research and scientific papers
Synthesis, inhibitory activity and in silico docking of dual COX/5-LOX inhibitors with quinone and resorcinol core
Sisa, Miroslav,Dvorakova, Marcela,Temml, Veronika,Jarosova, Veronika,Vanek, Tomas,Landa, Premysl
, (2020/07/31)
Based on the significant anti-inflammatory activity of natural quinone primin (5a), series of 1,4-benzoquinones, hydroquinones, and related resorcinols were designed, synthesized, characterized and tested for their ability to inhibit the activity of cyclooxygenase (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) enzymes. Structural modifications resulted in the identification of two compounds 5b (2-methoxy-6-undecyl-1,4-benzoquinone) and 6b (2-methoxy-6-undecyl-1,4-hydroquinone) as potent dual COX/5-LOX inhibitors. The IC50 values evaluated in vitro using enzymatic assay were for compound 5b IC50 = 1.07, 0.57, and 0.34 μM and for compound 6b IC50 = 1.07, 0.55, and 0.28 μM for COX-1, COX-2, and 5-LOX enzyme, respectively. In addition, compound 6d was identified as the most potent 5-LOX inhibitor (IC50 = 0.14 μM; reference inhibitor zileuton IC50 = 0.66 μM) from the tested compounds while its inhibitory potential against COX enzymes (IC50 = 2.65 and 2.71 μM for COX-1 and COX-2, respectively) was comparable with the reference inhibitor ibuprofen (IC50 = 4.50 and 2.46 μM, respectively). The most important structural modification leading to increased inhibitory activity towards both COXs and 5-LOX was the elongation of alkyl chain in position 6 from 5 to 11 carbons. Moreover, the monoacetylation in ortho position of bromo-hydroquinone 13 led to the discovery of potent (IC50 = 0.17 μM) 5-LOX inhibitor 17 (2-bromo-6-methoxy-1,4-benzoquinone) while bromination stabilized the hydroquinone form. Docking analysis revealed the interaction of compounds with Tyr355 and Arg120 in the catalytic site of COX enzymes, while the hydrophobic parts of the molecules filled the hydrophobic substrate channel leading up to Tyr385. In the allosteric catalytic site of 5-LOX, compounds bound to Tyr142 and formed aromatic interactions with Arg138. Taken together, we identified optimal alkyl chain length for dual COX/5-LOX inhibition and investigated other structural modifications influencing COX and 5-LOX inhibitory activity.
Concise access to primin, miconidin and related natural resorcinols
Sisa, Miroslav,Dvorakova, Marcela,Vanek, Tomas
, p. 5297 - 5301 (2017/08/04)
An efficient and short synthetic procedures affording the biologically active natural products primin, miconidin, olivetol, grevillol, and cardol (adipostatin A) in high yields are reported. The two strategies involve Sonogashira and Suzuki cross-couplings as the crucial steps for the installation of the alkyl side-chains. Syntheses start from cheap, commercially available 1-bromo-3,5-dimethoxybenezene to obtain 1,3-dimethoxy-5-(alk-1-yn-1-yl)benzene as the key intermediate. This intermediate can be easily and economically oxidized to provide primin in excellent overall yield while avoiding undesired side products by the virtue of its symmetry. The demethylation of the key intermediate affords natural resorcinols olivetol, grevillol, and cardol, respectively. The reduction of primin provides its hydroquinone derivative miconidin.
Synthesis and inhibitory activities against colon cancer cell growth and proteasome of alkylresorcinols
Zhu, Yingdong,Soroka, Dominique N.,Sang, Shengmin
, p. 8624 - 8631 (2012/11/13)
We have identified alkylresorcinols (ARs) as the major active components in wheat bran against human colon cancer cell growth (HCT-116 and HT-29) using a bioassay-guided approach. To further study the structure-activity relationships, 15 ARs and their intermediates (1-15) were synthesized expediently by the modified Wittig reaction in aqueous media, and six 5-alkylpyrogallols and their analogues (16-21) were prepared by the general Grignard reaction. The synthetic AR analogues were evaluated for activities against the growth of human colon cancer cells HCT-116 and HT-29 and the chymotrypsin-like activity of the human 20S proteasome. Our results found that (1) AR C13:0 and C15:0 (13 and 14) had the greatest inhibitory effects in human colon cancer cells HCT-116 and HT-29, while decreasing or increasing the side chain lengths diminished the activities; (2) two free meta-hydroxyl groups at C-1 and C-3 on the aromatic ring of the AR analogues greatly contributed to their antitumor activity; (3) the introduction of a third hydroxyl group at C-2 (20 and 21) into the aromatic ring of the AR analogues yielded no significant enhancement in activity against HCT-116 cells and decimated the effects against HT-29 cells, but dramatically increased the activity against the chymotrypsin-like activity of the human 20S proteasome; and (4) AR C11:0 (12) was found to have the greatest effect in a series of AR C9:0-C17:0 against the chymotrypsin-like activity of the human 20S proteasome.
Synthesis and biological evaluation of bilobol and adipostatin A
Tanaka, Ayano,Arai, Yasuhiro,Kim, Su-Nam,Ham, Jungyeob,Usuki, Toyonobu
experimental part, p. 290 - 296 (2011/06/19)
Concise total synthesis of bilobol 5-pentadecenylresorcinol (1), isolated from Gingko biloba fruits, has been achieved in 10 steps with 51% overall yield from 3,5-dihydroxybenzoic acid (3). Adipostatin A (2), isolated from the fruits as well as from Streptomyces cyaneus 2299-SV1, has also been synthesized in two steps from methylated bilobol (10). The structure-activity relationship study of synthetic products was described by means of cytotoxic assay against human KB carcinoma cell lines.
Phytotoxic activity of quinones and resorcinolic lipid derivatives
Mizuno, Cassia S.,Rimando, Agnes M.,Duke, Stephen O.
scheme or table, p. 4353 - 4355 (2011/08/05)
On the basis of the reported phytotoxic activity of sorgoleone and resorcinolic lipids identified from the root extracts of Sorghum bicolor, 8 resorcinolic lipid derivatives and 10 quinones with various side chain sizes were synthesized. The phytotoxicity of the compounds was tested against a monocot and a dicot species. The quinones were phytotoxic, whereas the resorcinolic lipids were not. Of the quinones, 2-hydroxy-5-methoxy-3- pentylcyclohexa-2,5-diene-1,4-dione, having a five-carbon side chain, showed phytotoxic activity similar to that of natural compound sorgoleone. This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society.
Alkylresorcylic acid synthesis by type III polyketide synthases from rice Oryza sativa
Matsuzawa, Miku,Katsuyama, Yohei,Funa, Nobutaka,Horinouchi, Sueharu
experimental part, p. 1059 - 1067 (2011/03/20)
Alkylresorcinols, produced by various plants, bacteria, and fungi, are bioactive compounds possessing beneficial activities for human health, such as anti-cancer activity. In rice, they accumulate in seedlings, contributing to protection against fungi. Alkylresorcylic acids, which are carboxylated forms of alkylresorcinols, are unstable compounds and decarboxylate readily to yield alkylresorcinols. Genome mining of the rice Oryza sativa identified two type III polyketide synthases, named ARAS1 (alkylresorcylic acid synthase) and ARAS2, that catalyze the formation of alkylresorcylic acids. Both enzymes condensed fatty acyl-CoAs with three C2 units from malonyl-CoA and cyclized the resulting tetraketide intermediates via intramolecular C-2 to C-7 aldol condensation. The alkylresorcylic acids thus produced were released from the enzyme and decarboxylated non-enzymatically to yield alkylresorcinols. This is the first report on a plant type III polyketide synthase that produces tetraketide alkylresorcylic acids as major products.
An expedient synthesis of 5-n-alkylresorcinols and novel 5-n-alkylresorcinol haptens
Parikka, Kirsti,Waehaelae, Kristiina
supporting information; experimental part, (2010/04/22)
The first synthesis of bioactive long alkyl chain 5-n-alkylresorcinols, present in whole grain products, by a novel modification of the Wittig reaction is described. All the main long chain 5-n-alkylresorcinols present in rye and wheat, including C23 and C25 analogues and haptens, which have not been previously prepared, were synthesised. Microwave-promoted reactions of a semistabilized ylid and alkanals in water gave good yields in both pressurized and open systems. An alternative microwave-promoted synthesis starting from non-stabilized alkyltriphenylphosphonium salts and 3,5-dimethoxybenzaldehyde worked as well. Aqueous media were suitable for the reactions even if the starting materials were not soluble in water. The 5-n-alkylresorcinols are potential biomarkers of whole grain intake, and the new hapten derivatives of 5-n-alkylresorcinols will open the way for the immunochemical detection techniques of alkylresorcinols.
Ultrasound-assisted Wittig reaction and synthesis of 5-alkyl- and 5-alkenyl-resorcinols
Wu, Li-Qiang,Yang, Chun-Guang,Yang, Li-Ming,Yang, Li-Juan
experimental part, p. 183 - 185 (2009/11/30)
Some 5-alkyl- and 5-alkenyl-resorcinols were synthesised from commercially available 3,5-bis(benzylo×y)benzaldehyde by ultrasound-assisted Wittig reaction with alkyltriphenyl phosphonium bromides in basic aqueous condition, followed by debenzylation and simultaneously reduction of a double bond of the styrene type with Na/n-BuOH in overall yields of 62-72%.
COMPOUNDS CAPABLE OF ABSORBING ULTRAVIOLET RADIATION, COMPOSITIONS CONTAINING THEM AND PROCESSES FOR THEIR PREPARATION
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Page/Page column 28, (2008/06/13)
The molecules capable of absorbing ultraviolet radiation from the cashew nut shell liquid changes are the object of the present invention; it is also described the compositions responsible for protecting the surfaces and chemical processes for the referred molecules production.
