- Lignosulfonate microcapsules for delivery and controlled release of thymol and derivatives
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Thymol and the corresponding brominated derivatives constitute important biological active molecules as antibacterial, antioxidant, antifungal, and antiparasitic agents. However, their application is often limited, because their pronounced fragrance, their poor solubility in water, and their high volatility. The encapsulation of different thymol derivatives into biocompatible lignin-microcapsules is presented as a synergy-delivering remedy. The adoption of lignosulfonate as an encapsulating material possessing relevant antioxidant activity, as well as general biocompatibility allows for the development of new materials that are suitable for the application in various fields, especially cosmesis. To this purpose, lignin microcapsules containing thymol, 4-bromothymol, 2,4-dibromothymol, and the corresponding O-methylated derivatives have been efficiently prepared through a sustainable ultrasonication procedure. Actives could be efficiently encapsulated with efficiencies of up to 50%. To evaluate the applicability of such systems for topical purposes, controlled release experiments have been performed in acetate buffer at pH 5.4, to simulate skin pH: all of the capsules show a slow release of actives, which is strongly determined by their inherent lipophilicity.
- Piombino, Claudio,Lange, Heiko,Sabuzi, Federica,Galloni, Pierluca,Conte, Valeria,Crestini, Claudia
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- Alkylphenol activity against candida spp. and microsporum canis: A focus on the antifungal activity of thymol, eugenol and o-methyl derivatives
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In recent years there has been an increasing search for new antifungal compounds due to the side effects of conventional antifungal drugs and fungal resistance. The aims of this study were to test in vitro the activity of thymol, eugenol, estragole and anethole and some O-methyl-derivatives (methylthymol and methyleugenol) against Candida spp. and Microsporum canis. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC). The minimum fungicidal concentrations (MFC) for both Candida spp. and M. canis were found by subculturing each fungal suspension on potato dextrose agar. Thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and griseofulvin respectively, presented the following MIC values against M. canis: 4.8-9.7; 78-150; 39; 78-150; 78-150; 19-39 μg/mL and 0.006-2.5 μg/mL. The MFC values for all compounds ranged from 9.7 to 31 μg/mL. Concerning Candida spp, thymol, methylthymol, eugenol, methyleugenol, anethole, estragole and amphotericin, respectively, showed the following MIC values: 39; 620-1250; 150-620; 310-620; 620; 620-1250 and 0.25-2.0 μg/mL. The MFC values varied from 78 to 2500 μg/mL. All tested compounds thus showed in vitro antifungal activity against Candida spp. and M. canis. Therefore, further studies should be carried out to confirm the usefulness of these alkylphenols in vivo.
- Fontenelle, Raquel O.S.,Morais, Selene M.,Brito, Erika H.S.,Brilhante, Raimunda S.N.,Cordeiro, Rossana A.,Lima, Ynayara C.,Brasil, Nilce V.G.P.S.,Monteiro, Andre J.,Sidrim, Jose J.C.,Rocha, Marcos F.G.
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- Structural revision of aristol: A fresh look at the oxidative coupling of thymol under iodination conditions
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Aristol, an antiseptic drug prepared by iodination of thymol under alkaline conditions, has been on the market since the 1880s. Up until 1951, a myriad of (unlikely) structures were put forward, but none of them were in full agreement with the observed chemical and physical properties of aristol. Today, according to most pharmacopoeias and commercial sources, aristol represents an iodooxybiphenyl derivative; the origin of this structure is unknown. Motivated by these facts, we decided to elucidate the structure of aristol using modern chromatographic and extensive spectrometric techniques (NMR/FTIR/MS/UV), combined with chemical transformations and quantum mechanical calculations. Based on our findings, it was revealed that aristol does not represent a single chemical entity but a complex mixture of a large number of structurally closely related iodinated dehydrodithymol molecules together with (di)iodothymols and unreacted thymol. Five products of oxidative coupling (CAr-CAr, CAr-O-CAr and CAr-CH2-CAr) were successfully isolated in a pure state and fully spectrally characterized: 3,3′-diiodo-5,5′-diisopropyl-2,2′-dimethyl-[1,1′-biphenyl]-4,4′-diol, 5,5′-diiodo-3,3′-diisopropyl-6,6′-dimethyl-[1,1′-biphenyl]-2,2′-diol, 2-iodo-4-(4-iodo-2-isopropyl-5-methylphenoxy)-6-isopropyl-3-methylphenol, 4-(5-hydroxy-2-iodo-4-isopropylbenzyl)-2-isopropyl-5-methylphenol, and 3-(4-hydroxy-5-isopropyl-2-methylbenzyl)-2,4-diiodo-6-isopropylphenol. A lateral meta-coupling (with respect to the phenoxy-radical), CAr-CH2-CAr, previously never reported for oxidative coupling of phenols, was firmly established in two aristol constituents. This provides evidence for a mechanism that involves benzyl radicals unknown to form under these conditions. An additional 16 aristol constituents were identified by the use of a QSPR model (readily available structure-derived descriptors used to predict gas chromatography retention data), in combination with mass spectrometry, directly from the aristol matrix without preparative chromatography. The herein presented results urge a revision of the currently accepted formula (composition) of aristol in both primary and secondary literature.
- Radulovi?, Niko S.,Dordevi?, Miljana R.,Blagojevi?, Polina D.
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- Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors
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In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06±0.4μM. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.
- Alokam, Reshma,Jeankumar, Variam Ullas,Sridevi, Jonnalagadda Padma,Matikonda, Siddharth Sai,Peddi, Santosh,Alvala, Mallika,Yogeeswari, Perumal,Sriram, Dharmarajan
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- Biotechnological Potential of Eugenol and Thymol Derivatives Against Staphylococcus aureus from Bovine Mastitis
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Bovine mastitis is an infectious disease that affects the mammary gland of dairy cattle with considerable economic losses. Staphylococcus aureus is the main microorganism involved in this highly contagious process, and the treatment is only using antibiotics. Currently, the search for new treatment and/or compounds is still in need due to microbial resistance. In this work, we evaluated the potential of eugenol and thymol derivatives against S. aureus strains from bovine mastitis. On that purpose, nine derivatives were synthesized from eugenol and thymol (1–9), and tested against 15 strains of S. aureus from subclinical bovine mastitis. Initially, the strains were evaluated for the biofilm production profile, and those with strong adherence were selected to the antimicrobial sensitivity determination in the Minimum Inhibitory Concentration (MIC) assays. Herein the compounds toxicity was also evaluated by in silico analysis using Osiris DataWarrior software. The results showed that 60% of the strains were considered strongly adherent and three strains (S. aureus 4271, 4745 and 4746) were selected for the MIC tests. Among the nine eugenol and thymol derivatives tested, four were active against the evaluated strains (MIC = 32?μg?mL?1) within CLSI standard values. In silico analysis showed that all derivatives had cLopP ??4 and TPSA 140 ?2, and similar theoretical toxicity parameters to some antibiotics currently on the market. These molecules also showed negative drug-likeness values, pointing to the originality of these structures and theoretical feasibility on escaping of resistance mechanism and act against resistant strains. Thus, these eugenol derivatives may be considered as promising for the development of new treatments against bovine mastitis and future exploring on this purpose.
- Nunes, Daiana O. S.,Vinturelle, Rafaelle,Martins, Francislene J.,dos Santos, Thiago F.,Valverde, Alessandra Leda,Ribeiro, Carlos Magno R.,Castro, Helena C.,Folly, Evelize
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p. 1846 - 1855
(2021/04/29)
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- Antioxidant and tyrosinase docking studies of heterocyclic sulfide derivatives containing a thymol moiety
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Fourteen heterocyclic sulfide derivatives (4–17) containing a thymol moiety and oxadiazole, thiadiazole, triazole, oxazole, thiazole, imidazole, pyridine or purine heterocycles were synthesized in three steps. The cupric, Cu(II), ion reducing antioxidant capacity of the compounds was examined, and molecular docking studies were performed to determine whether the sulfur, thymol or heterocyclic moieties interact with the Cu ions in tyrosinase, a type-3 copper enzyme. Using the CUPRAC assay, eight compounds (5–8, 10, 15–17) showed equal or better Cu (II) reducing capacity than trolox at neutral pH, with trolox equivalent antioxidant capacity (TEAC) coefficients ranging between 1.00 and 1.48. The compounds containing a thiadiazole moiety were most effective, with the methyl thiadiazole derivative (8) having the highest Cu(II) reducing capacity. Molecular docking studies of the sulfide derivatives with tyrosinase revealed that there were no direct interactions between the sulfur atom and the active site copper ions. However, the compounds displayed two different binding interactions with the histidine-Cu catalytic center. For compounds 4–13, the thymol portion was embedded in the active site cavity, while for compounds 14–17 the heterocyclic portion of the molecule approached the cavity.
- Havasi, Mia H.,Ressler, Andrew J.,Parks, Eden L.,Cocolas, Alexander H.,Weaver, Ashton,Seeram, Navindra P.,Henry, Geneive E.
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- Structure-Odor Activity Studies on Derivatives of Aromatic and Oxygenated Monoterpenoids Synthesized by Modifying p-Cymene
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Thymoquinone was recently reported as having a unique pencil-like odor and being the impact compound for the cedar-like and cedar wood-based product smell such as pencils. The compounds thymol and carvacrol are structurally related odorants commonly found in plants and foods such as thyme and oregano, also having a significant contribution to their overall aroma. However, a systematic elucidation of the sensory properties in this class of oxygenated, aromatic monoterpenoids has not been carried out. To close this gap and gain new insights into structure-odor relationships leading to pencil-like and woody odors, 19 structurally related derivatives of p-cymene starting from thymol and carvacrol were synthesized and characterized. The compounds had odor thresholds ranging from 2.0 ng/L air to 388.8 ng/L air, being lowest for thymol and carvacrol and highest for thymohydroquinone. The compounds smelled mostly thyme-like, oregano-like, and pencil-like with phenolic, earthy, and medicinal variations in their odor character, which could be successfully linked to structural motifs.
- Schreiner, Linda,Bauer, Johannes,Ortner, Eva,Buettner, Andrea
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supporting information
p. 834 - 842
(2020/03/30)
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- Phenylimidazole derivative, synthesis method of phenylimidazole derivative and application of phenylimidazole derivative to pesticide
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The invention relates to a phenylimidazole derivative, a synthesis method of the phenylimidazole derivative and application of the phenylimidazole derivative to pesticide, particularly application tothe fungicide pesticide aspect, and belongs to the technical field of pesticide. In order to solve the technical problems, the invention provides a novel phenylimidazole derivative, a synthesis methodof the novel phenylimidazole derivative and application of the novel phenylimidazole derivative to the pesticide. The structure of the compound is shown as a formula I. The compound structure is simple and novel; the synthesis is easy; meanwhile, the fungicidal activity is realized; a better bacteriostasis or sterilization effect is achieved on important plant pathogenic fungi such as tomato early blight, tomato botrytis cinereal, cucumber fusarium oxysporum, magnaporthe grisea and rice rhizoctonia solani.
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Paragraph 0051
(2019/06/11)
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- Synthesis of thymol-based pyrazolines: An effort to perceive novel potent-antimalarials
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A series of thymol based substituted pyrazolines and chalcones was synthesized and evaluated for antimalarial activity, using in-vitro and in-vivo malaria models. All the target compounds (5a-k and 6a-j)were found to be active against human malaria parasite strain Plasmodium falciparum NF54. Among all, compounds 5e and 5f of chalcone series and 6c and 6f of pyrazoline series exhibited prominent antimalarial activity with IC50 less than 3 and 2 μM respectively, while other pyrazolines also significantly inhibited the P. falciparum with IC50 less than 10 μM. The designed pharmacophores were found to be effective against P. falciparum. Compound 6f was found to be able to retard malaria progression in mice. This was evident through decreased parasitemia, increased mean survival time and hemoglobin content in the treated animals. Moreover, 6f was observed as an inhibitor of heme polymerization pathway of the malaria parasite. It also inhibited free heme degradation, which could be possibly responsible for higher reactive oxygen species (ROS)in parasite, thus inhibiting the rapid proliferation of the parasite. In addition to this, compound 6f was found to be non-toxic with a good selectivity index. Based on these observations, the compound 6f could be taken up for further antimalarial lead optimization studies.
- Raghuvanshi, Dushyant Singh,Verma, Narsingh,Singh, Shiv Vardan,Khare, Sonam,Pal, Anirban,Negi, Arvind Singh
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supporting information
(2019/05/01)
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- Active Molybdenum-Based Anode for Dehydrogenative Coupling Reactions
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A new and powerful active anode system that can be operated in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher-valent molybdenum species. This system can replace powerful but stoichiometrically required MoV reagents for the dehydrogenative coupling of aryls. This electrolytic reaction is more sustainable and allows the conversion of a broad scope of activated arenes.
- Beil, Sebastian B.,Müller, Timo,Sillart, Sydney B.,Franzmann, Peter,Bomm, Alexander,Holtkamp, Michael,Karst, Uwe,Schade, Wolfgang,Waldvogel, Siegfried R.
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supporting information
p. 2450 - 2454
(2018/02/09)
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- Efficient cross-coupling of aryl/alkenyl triflates with acyclic secondary alkylboronic acids
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Aryl-secondary alkyl cross-coupling with aryl sulfonate esters as coupling partners remains a significant challenge. Efficient cross-coupling between aryl/alkenyl triflates and acyclic secondary alkylboronic acids is realized for the first time to provide a series of sterically congested acyclic secondary alkyl arenes/olefins in good to excellent yields. The employment of sterically bulky P,PO ligand L1/L2 is crucial for the high yields and selectivities. The method has enabled a concise and 4-step synthesis of a key intermediate of male contraceptive agent and PAF antagonist gossypol.
- Si, Tengda,Li, Bowen,Xiong, Wenrui,Xu, Bin,Tang, Wenjun
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supporting information
p. 9903 - 9909
(2017/12/12)
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- Synthesis of halogenated derivatives of thymol and their antimicrobial activities
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In order to test the antibacterial and antifungal activities of different halogenated thymol derivatives, thymol has been converted into chlorothymol, dichlorothymol with N-chlorosuccinimide; monobromothymol, dibromothymol with N-bromosuccinimide; O-methylated iodothymol with ceric ammonium nitrate and iodine from methylated thymol. Among the different derivatives tested, 4-chlorothymol was found to be most active against Staphylococcus aureus and Staphylococcus epidermis at a concentration of 12.5 and 25 ppm, respectively. Also it was tested to be active against Candida albicans (AI). Springer Science+Business Media 2013.
- Kaur, Ranjeet,Darokar, Mahendra P.,Chattopadhyay, Sunil Kumar,Krishna, Vinay,Ahmad, Ateeque
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p. 2212 - 2217
(2014/05/06)
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- Sequential Birch reaction and asymmetric Ir-catalyzed hydrogenation as a route to chiral building blocks
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A range of 1,2,4-trisubstituted cyclohexadienes obtained from the Birch reaction were hydrogenated asymmetrically to produce synthetically valuable chiral compounds in high enantio- and diastereoselectivity. The Royal Society of Chemistry.
- Paptchikhine, Alexander,Itto, Kaori,Andersson, Pher G.
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supporting information; experimental part
p. 3989 - 3991
(2011/06/09)
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- Synthesis of aryl alkyl ethers by alkylation of phenols with quaternary ammonium salts
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Phenolic compounds can be efficiently O-methylated with tetramethylammonium chloride in diglyme or polyethyleneglycol (PEG) at temperatures of 150-160 °C and in the presence of either K2CO3 or NaOH. When applying benzyl-trimethylammonium chloride as a reagent, the benzylation and methylation of phenols occurs, with the benzylation product always predominating. With allyl-substituted phenols as substrates and using NaOH as a base it was possible to achieve both the alkylation and the double-bond isomerization of the allyl group to obtain (E/Z)-propenyl-substituted methyl and benzyl aryl ethers in a single preparative step.
- Maras, Nenad,Polanc, Slovenko,Kocevar, Marijan
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experimental part
p. 29 - 36
(2010/09/05)
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- Microwave-assisted methylation of phenols with tetramethylammonium chloride in the presence of K2CO3 or Cs2CO3
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We have evaluated the potential of using tetramethylammonium chloride (Me4NCl) as an alternative methylating agent for phenols under microwave-assisted conditions. Its chemical behavior was tested in a reaction with 2-naphthol in the presence of various bases and solvents. The method was then applied in 1,2-dimethoxyethane or toluene under heterogeneous conditions for the O-methylation of a series of phenolic compounds. We found that many simple phenols can be methylated in the presence of K2CO3, whereas some other less-reactive phenols require the presence of the more reactive Cs2CO3.
- Mara?, Nenad,Polanc, Slovenko,Ko?evar, Marijan
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experimental part
p. 11618 - 11624
(2009/04/05)
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- Microwave-assisted sinthesis of thymyl ethers and esters in aqueous medium
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Various thymyl ethers and esters have been synthesized by reactions of thymol with alkyl halides and acid chlorides, respectively, in aqueous medium under environmentally benign conditions using microwave irradiation. The products are important as potent pest managing agents.
- More,Pawar,Dewang,Patil,Mahulikar
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p. 217 - 218
(2007/10/03)
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