- Chemical profile of lippia thymoides, evaluation of the acetylcholinesterase inhibitory activity of its essential oil, and molecular docking and molecular dynamics simulations
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The essential oils of the fresh and dry flowers, leaves, branches, and roots of Lippia thymoides were obtained by hydrodistillation and analyzed using gas chromatography (GC) and GC-mass spectrometry (MS). The acetylcholinesterase inhibitory activity of the essential oil of fresh leaves was investigated on silica gel plates. The interactions of the key compounds with acetylcholinesterase were simulated by molecular docking and molecular dynamics studies. In total, 75 compounds were identified, and oxygenated monoterpenes were the dominant components of all the plant parts, ranging from 19.48% to 84.99%. In the roots, the main compounds were saturated and unsaturated fatty acids, having contents varying from 39.5% to 32.17%, respectively. In the evaluation of the anticholinesterase activity, the essential oils (detection limit (DL) = 0.1 ng/spot) were found to be about ten times less active than that of physostigmine (DL = 0.01ng/spot), whereas thymol and thymol acetate presented DL values each of 0.01 ng/spot, equivalent to that of the positive control. Based on the docking and molecular dynamics studies, thymol and thymol acetate interact with the catalytic residues Ser203 and His447 of the active site of acetylcholinesterase. The binding free energies (ΔGbind) for these ligands were -18.49 and -26.88 kcal/mol, demonstrating that the ligands are able to interact with the protein and inhibit their catalytic activity.
- Silva, Sebasti?o Gomes,Da Costa, Renato Araujo,Figueiredo, Pablo Luis B.,Do Socorro Barros Brasil, Davi,De Aguiar Andrade, Eloisa Helena,De Oliveira, Mozaniel Santana,De Carvalho, Raul Nunes,Da Cruz, Jorddy Neves,De Jesus Chaves Neto, Antonio Maia,Nascimento, Lidiane Diniz
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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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- Environmentally benign decarboxylative: N-, O-, and S-Acetylations and acylations
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An operationally simple and general method for acetylation and acylation of a wide variety of substrates (amines, alcohols, phenols, thiols, and hydrazones) has been reported. Meldrum's acid and its derivatives have been used as an air-stable, non-volatile, cost-effective, and easy to handle acetylating/acylating agent. Easily separable byproducts (CO2 and acetone) allowed the isolation of analytically pure acetylated products without the requirement of work-up and any chromatography. This journal is
- Ghosh, Santanu,Purkait, Anisha,Jana, Chandan K.
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supporting information
p. 8721 - 8727
(2020/12/30)
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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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- INSECTICIDAL COMPOSITION
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PROBLEM TO BE SOLVED: To provide a composition that can exhibit effective insecticidal action on insect pests. SOLUTION: An insecticidal composition comprises, e.g., a compound represented by general formula (1) in the figure. [R1 is a C1-10 alkyl group or the like, where the alkyl group and the like may be substituted with a halogen atom or the like; R2 is a hydrogen atom or the like, or R2 may bind a methoxy group binding a carbon atom adjacent to a carbon atom which R2 binds, to form a -O-CH2-O- group.] SELECTED DRAWING: None COPYRIGHT: (C)2021,JPO&INPIT
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Paragraph 0063-0064
(2020/10/27)
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- Unprecedented acetylation of phenols using a catalytic amount of magnesium powder
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The acetylation of phenols with acetic anhydride was achieved using a catalytic amount of magnesium metal powder under air and solvent-free conditions to afford corresponding phenyl acetates in excellent yield (up to 98%).
- Bajracharya, Gan B.,Shrestha, Suryaman Sama
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supporting information
p. 1688 - 1693
(2018/06/15)
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- Antifungal activity of phenolic monoterpenes and structure-related compounds against plant pathogenic fungi
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The aim of this work is to explore the possibility of using the phenolic monoterpenes (PMs) as leading compounds with antifungal activity against plant disease. The in vitro antifungal activities of carvacrol and thymol against seven kinds of plant pathogenic fungi were evaluated on mycelium growth rate method, and the results showed that carvacrol and thymol exhibited broad spectrum antifungal activity. Structure requirement for the antifungal activity of PMs was also investigated. The preliminary conclusion was that phenolic hydroxyl and monoterpene were basic structures for the antifungal activity of PMs, and the position of phenolic hydroxyl showed less effect. Ester derivatives of carvacrol and thymol were more effective than carvacrol and thymol against plant pathogenic fungi. We suggested that carvacrol, thymol and their ester derivatives could potentially be used as new fungicide leading compounds.
- Wang, Kaibo,Jiang, Shanshan,Pu, Te,Fan, Liming,Su, Fawu,Ye, Min
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- Synthesis, antimicrobial activity and in silico studies on thymol esters
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Derivatisation of parent structure in terpenoids often results in enhancement of biological activity of newly obtained compounds. Thymol, a naturally occurring phenol biosynthesized through the terpene pathway, is a well known biocide with strong antimicrobial attributes and diverse therapeutic activities. We have aimed our study on a single modification of phenolic functionality in thymol in order to obtain a small focused library of twenty thymyl esters, ten of which were new compounds. All compounds were involved in in vitro antimicrobial testing. Another important aspect of current study was implementation of in silico calculation of physico-chemical, pharmacokinetic and toxicological properties, which could be helpful by giving an additional guidance in further research.
- Lazarevi?, Jelena,Kolarevi?, Ana,Dordevi?, Aleksandra,Stojanovi?, Gordana,?melcerovi?, Andrija,Ciuffreda, Pierangela,Santaniello, Enzo
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p. 603 - 612
(2017/09/11)
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- INSECTICIDAL COMPOSITION
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PROBLEM TO BE SOLVED: To provide a composition that can exhibit effective insecticidal action on pests. SOLUTION: An insecticidal composition comprises a compound represented by general formula (1) [R1 is a C1-10 alkyl group or the like, where the alkyl group and the like may be substituted with a halogen atom and the like; R2 is a hydrogen atom and the like, or R2 may bind a methoxy group binding a carbon atom adjacent to a carbon atom which R2 binds, to form a -O-CH2-O- group]. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0063
(2017/09/29)
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- Thymol and eugenol derivatives as potential antileishmanial agents
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In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5-10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100 mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis.
- De Morais, Selene Maia,Vila-Nova, Nadja Soares,Bevilaqua, Claudia Maria Leal,Rondon, Fernanda Cristina,Lobo, Carlos Henrique,De Alencar Araripe Noronha Moura, Arlindo,Sales, Antnia Dbora,Rodrigues, Ana Paula Ribeiro,De Figuereido, Jos Ricardo,Campello, Claudio Cabral,Wilson, Mary E.,De Andrade, Heitor Franco
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p. 6250 - 6255
(2015/02/02)
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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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p. 547 - 554
(2014/08/05)
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- Synthesis and evaluation of antioxidant and antimicrobial properties of thymol containing pyridone moieties
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Various derivatives of 1,2-dihydro-6-(4-hydroxy- 5-isopropyl-2- methylphenyl)-2-oxo-4-arylpyridine-3-carbonitrile (IVa-m) were synthesized and characterized. Their antioxidant and antimicrobial properties were evaluated by measuring their activity in vitro. Among the newly synthesized derivatives IVg, IVh, IVi, IVj, IVk, IVl, and IVm showed good antioxidant activity. However, all derivatives show better antibacterial and antifungal properties than that of parent thymol. The probable mechanism, particularly for antioxidant properties of these compounds is proposed. Springer Science+Business Media, LLC 2011.
- Nagle,Pawar,Sonawane,Bhosale,More
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experimental part
p. 1395 - 1402
(2012/07/31)
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- Antinociceptive effect of extracts and compounds from Hofmeisteria schaffneri
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Ethnopharmacological relevance: Hofmeisteria schaffneri (Asteraceae) is a medicinal plant widely commercialized in the most important Markets of Mexico City for the treatment of gastro-intestinal complaints and skin afflictions. Aim of the study: The main goals of this study were to establish the potential acute toxicity and the antinociceptive activity in animal models of several preparations and compounds from Hofmeisteria schaffneri. Materials and methods: The aqueous and organic extracts as well as the essential oil of Hofmeisteria schaffneri were prepared by infusion, maceration and hydrodistillation, respectively. Investigation of the acute toxicity was accomplished by the Lorke method. The antinociceptive effect was assessed using the writhing and the hot plate tests. Natural compounds were isolated by standard phytochemical procedures. In addition, a few thymol esters were prepared by chemical synthesis. The stability of natural and synthetic esters was qualitatively analyzed by measuring their susceptibility to hydrolysis by pig liver estearase and mouse plasma at 37°C. Results: The LD50 for each preparation tested was higher than 5000mg/kg revealing that they were not toxic to mice after exposure for short space of time. On the other hand, the extracts showed significant antinociceptive effect when tested in the hot plate model. The most active natural product as antinociceptive agent was hofmeisterin III (1) which also was the most stable in the stability study. Its pharmacological effect seems to be partially mediated by an opioid mechanism since naloxone inhibits its action. Using compound 1 as a lead molecule, several synthetic thymol esters were prepared and only compounds 13, 15 and 17 were antinoceptive at the dose of 1mg/kg. Conclusions: The present investigation provided evidence of the efficacy of several preparations of Hofmeisteria schaffneri as antinociceptive agents. The most active preparation was the essential oil which contained large amount of hofmeisterin III (1) and other thymol derivatives. Some novel synthetic analogs of hofmeisterin III with antinociceptive properties were discovered. The nature of the ester chain of these analogs did not have a clear impact on the antinociceptive activity. The phyto-preparations analyzed in this study were not toxic to mice according to the Lorke's test; therefore considering their long term use of the plant they might be secure for human consumption.
- Angeles-Lopez, Guadalupe,Perez-Vasquez, Araceli,Hernandez-Luis, Francisco,Deciga-Campos, Myrna,Bye, Robert,Linares, Edelmira,Mata, Rachel
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experimental part
p. 425 - 432
(2011/11/14)
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- Synthesis and in vitro antibacterial activity of thymol and carvacrol derivatives
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Fourteen esters of thymol and carvacrol were synthesized and characterized on the basis of spectral data. The NMR data for some of these are being given for the first time. The antibacterial activity screening of thymol, carvacrol and their esters were carried out against four Gram-positive (Streptococcus mutans MTCC 890, Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus epidermidis MTCC 435) and one Gram-negative (Escherichia coli MTCC 723) bacteria. The enhancement in activity was noticed in the thymyl ester derivatives 4a-c (against S. mutans, B. subtilis and S. epidermidis) in comparison to thymol, whereas the carvacrol derivatives were found to be much less active than carvacrol.
- Mathela, Chandra S.,Singh, Krishna K.,Gupta, Vivek K.
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experimental part
p. 375 - 380
(2011/08/06)
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- Commercial zinc oxide (Zn2+) as an efficient and environmentally benign catalyst for homogeneous benzoylation of hydroxyl functional groups
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The solvent-free O-acylation of some alcohols with benzoyl chloride was carried out to the corresponding benzoylated products in good to excellent yields by the mediation of a catalytic amount (5 mol%) of the commercially available and inexpensive zinc oxide in short reaction times. This methodology represents an eco-friendly and simple catalytic alternative for benzoylation of primary, secondary, tertiary, and benzylic alcohols with ZnO. This catalytic system was homogeneous because of high solubility of zinc oxide in the reaction medium. Findings showed that ZnO was dissolved in hydrochloric acid, created in situ, after a few minutes. Although, others argued on the catalytic role of solid phase zinc oxide under a heterogeneous condition, it is not surprising to emphasize on the catalytic function of Zn2+ in the benzoylation of alcohols under homogeneous reaction conditions. Zinc oxide served as pre-catalyst to form Zn2+, as the catalytically active species.
- Tayebee, Reza,Cheravi, Fatemeh,Mirzaee, Mehdi,Amini, Mojtaba M.
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experimental part
p. 1247 - 1252
(2010/11/17)
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- Samarium trifluoromethanesulfonate: An efficient moisture tolerant acylation catalyst under solvent-free condition
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Samarium trifluoromethanesulfonate catalyzed the acylation of phenols, alcohols, thiols, free reducing sugars, and glycosides in excellent yields at ambient temperature under solvent-free condition using stoichiometric amounts of various anhydrides. (Chemical Equation Presented). Copyright Taylor & Francis Group, LLC.
- Roy, Bimalendu,Dasgupta, Somnath,Kumar Rajput, Vishal,Mukhopadhyay, Balaram
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- A novel route to produce thymol by vapor phase reaction of m-cresol with isopropyl acetate over Al-MCM-41 molecular sieves
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Mesoporous Al-MCM-41 (Si/Al = 55 and 104) and Al,Zn-MCM-41 (Si/(Al+Zn)=52) molecular sieves were synthesized hydrothermally. The materials were characterized by XRD, TGA, TPD (pyridine), ICP-AES, nitrogen sorption, and FT-IR techniques. The catalytic performance of these materials was examined in the vapor phase alkylation of m-cresol with isopropyl acetate. The products obtained were thymol, isothymol, 2-isopropyl-5-methylphenyl acetate (2-I-5-MPA), and isopropyl-3-methylphenyl ether (I-3-MPE). The time-on-stream study was carried out over Al-MCM-41(55) at 300°C and WHSV 1.52 h-1 wherein optimum conversion of m-cresol and selectivity to thymol were obtained. The dependence of activity and selectivity on the acid sites and hydrophobic and hydrophilic properties of the catalysts is discussed.
- Shanmugapriya,Palanichamy,Arabindoo, Banumathi,Murugesan
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p. 347 - 357
(2007/10/03)
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- Microwave-assisted NiCl2 promoted acylation of alcohols
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A microwave oven acylation of alcohols by carboxylic acid anhydrides has been developed. NiCl2 has been proven an efficient catalyst for the acylation of primary, secondary, and tertiary alcohols and phenols under microwave conditions.
- Constantinou-Kokotou, Violetta,Peristeraki, Anna
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p. 4227 - 4232
(2007/10/03)
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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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- Reactions of some terpenes and their derivatives with acylating agents in the presence of aluminosilicate catalysts
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Reactions of camphene, α-fenchene, limonene, caryophyllene, α- and β-pinenes, verbenol, walterol, and verbenone with acylating agents in the presence of clay K-10 and wide-porous β-zeolite were studied. Presumable schemes and rules of the occurring proces
- Volcho,Tatarova,Suslov,Korchagina,Salakhutdinov,Barkhash
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p. 1418 - 1429
(2007/10/03)
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- Regioselective fries rearrangement and friedel-crafts acylation as efficient routes to novel enantiomerically enriched ortho-acylhydroxy[2.2]paracyclophanes
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Two useful approaches to ortho-acylhydroxy[2.2]paracyclophanes, starting from 4-hydroxy[2.2]paracyclophane, have been developed. TiCl4-catalyzed Fries rearrangement and direct acylation occur regioselectively (to the ortho position with respect to the hydroxy group), leading to 4-acetyl-5-hydroxy[2.2]paracyclophane (3) and 4-benzoyl-5-hydroxy[2.2]-paracyclophane (4) in high to excellent chemical yields. For compound 4, an X-ray investigation has been performed. ortho-Acylhydroxy[2.2]paracyclophanes 3 and 4 have been obtained in enantiomerically enriched forms (ee 92-99%) and the absolute configurations of their enantiomers have been determined.
- Rozenberg, Valeria,Danilova, Tat'yana,Sergeeva, Elena,Vorontsov, Evgenii,Starikova, Zoya,Lysenko, Konstantin,Belokon', Yuri
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p. 3295 - 3303
(2007/10/03)
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- BF3-induced cyclobutane-opening of verbenone and its deconjugate homolog. Efficient preparation of o-mentha-1,8-dien-3-one and o-menth-1-en- 3-one in optically active forms
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Starting with (+)-verbenone, readily obtainable from (+)-nopinone, enantioselective preparation of (S)-(+)-4-isopropenyl-, (S)-(-)-4-isopropyl- and (R)-(+)-4-(1-acetoxy-1-methylethyl)-3-methyl-2-cyclohexen-1-ones was accomplished with little loss of stereochemical integrity via BF3-induced cyclobutane-opening of (+)4-(methylene)nopinone. As we have developed an efficient chemical transformation of (+)-nopinone into (-)-verbenone, the present syntheses of the above cyclohexenones are formal syntheses of their enantiomers from (+)-nopinone.
- Kusakari, Takashi,Ichiyanagi, Tsuyoshi,Kosugi, Hiroshi,Kato, Michiharu
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p. 339 - 346
(2007/10/03)
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- Solid state acetylation with acetylimidazole: Selective protection of primary alcohols and phenols
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Primary alcohols and phenols have been acetylated with acetylimidazole by the solid state reaction, grinding both substrates with a pestle in a mortar.
- Hagiwara, Hisahiro,Morohashi, Kimie,Suzuki, Toshio,Ando, Masayoshi,Yamamoto, Isao,Kato, Michiharu
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p. 2001 - 2006
(2007/10/03)
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- Retention behavior of compounds with active hydrogen atoms and their acetylated derivatives in reversed-phase HPLC
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In view of poor interlaboratory reproducibility of retention indices I in reversed-phase high-performance liquid chromatography, not the indices themselves but their differences for reactants and products of interaction with various reagents can be used to identify compounds with active hydrogen atoms. For acetylated derivatives of phenols and aromatic amines, the quantity ?I = I(ArXH) -I(ArXCOCH3), where X = O or NH. has statistically significant distinguishable values of 126 ± 15 and 70 ± 20, respectively. The additivity of the parameters ?I is first revealed for the polyfunctional compounds of these classes that are incapable of intramolecular hydrogen bonding. Abnormal ?I values and deviations from the additivity rule are observed only for substances with intramolecular hydrogen bonding. This finding can be used to confirm the presence of relevant structural units in molecules.
- Zenkevich,Kosman
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p. 1173 - 1176
(2007/10/03)
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- Acetylation of Polymer Supported Phenoxides by Acetic Anhydride in Non-Aqueous Medium
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Polymer supported phenoxide anions have been acetylated to the corresponding acetates in excellent yields, using an excess of acetic anhydride at room temperature.
- Ram, B.,Roy, J.,Sarkar, A.
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- Benzocyclization of 2,4-Hexadienoic Acids. Synthesis of (R)-(-)-Curcuphenol Acetate
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A simple and general benzocyclization sequence, useful in the conversion of α-methylene ketones/aldehydes 1a-f to phenolic acetates 6a-g via the dienoic acids 5a-g is presented.The technique has provided a new route to the terpenoids, thymol acetate (6f) and (R)-(-)-curcuphenol acetate (6g).
- Murali, D.,Rao, G. S. Krishna
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p. 254 - 256
(2007/10/02)
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