Thymol isobutyrate

Antioxidant and Leishmanicidal Evaluation of Pulicaria Inuloides Root Extracts: A Bioguided Fractionation.[Pubmed:31652669]

Pathogens. 2019 Oct 23;8(4). pii: pathogens8040201.

Leishmaniasis remains a major world health problem, and in particular, Algeria ranks second for the incidence of cutaneous leishmaniasis. Pulicaria inuloides is a well-known Arabian Peninsula medicinal plant. In the present study, the chloroform, ethyl acetate and n-butanol extracts from the roots of Pulicaria inuloides were analyzed for antioxidant activity and its correlation with the total phenolic and flavonoid contents. The highest antioxidant activity using a DPPH assay was showed by the ethyl acetate extract (IC50 4.08 microg/mL), which also had the highest total phenolic content (307.12 microgAGE). Furthermore, P. inuloides root extracts were evaluated against Leishmania amazonensis and Leishmania donovani. The results highlighted the chloroform extract as the most active one against both tested Leishmania strains. A bioguided fractionation of the chloroform extract led to the isolation of (8R:8S)-(75:25 er)-10-isobutyryloxy-8,9-epoxy-Thymol isobutyrate as the main bioactive component, showing a potent leishmanicidal activity on L. amazonensis promatigote and amastigote stages (IC50 5.03 and 2.87 microM, respectively) and a good selectivity index on murine macrophages (CC50 19.37 microM). This study provides the first report of the antioxidant and leishmanicidal activities of P. inuloides root extracts and the results point to this species as a source of potential bioactive agents.

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of Ageratina glabrata.[Pubmed:29278331]

J Nat Prod. 2018 Jan 26;81(1):63-71.

A methodology to determine the enantiomeric excess and the absolute configuration (AC) of natural epoxythymols was developed and tested using five constituents of Ageratina glabrata. The methodology is based on enantiomeric purity determination employing 1,1'-bi-2-naphthol (BINOL) as a chiral solvating agent combined with vibrational circular dichroism (VCD) measurements and calculations. The conformational searching included an extensive Monte Carlo protocol that considered the rotational barriers to cover the whole conformational spaces. (+)-(8S)-10-Benzoyloxy-6-hydroxy-8,9-epoxyThymol isobutyrate (1), (+)-(8S)-10-acetoxy-6-methoxy-8,9-epoxyThymol isobutyrate (4), and (+)-(8S)-10-benzoyloxy-6-methoxy-8,9-epoxyThymol isobutyrate (5) were isolated as enantiomerically pure constituents, while 10-isobutyryloxy-8,9-epoxyThymol isobutyrate (2) was obtained as a 75:25 (8S)/(8R) scalemic mixture. In the case of 10-benzoyloxy-8,9-epoxyThymol isobutyrate (3), the BINOL methodology revealed a 56:44 scalemic mixture and the VCD measurement was beyond the limit of sensitivity since the enantiomeric excess is only 12%. The racemization process of epoxythymol derivatives was studied using compound 1 and allowed the clarification of some stereochemical aspects of epoxythymol derivatives since their ACs have been scarcely analyzed and a particular behavior in their specific rotations was detected. In more than 30 oxygenated thymol derivatives, including some epoxythymols, the reported specific rotation values fluctuate from -1.6 to +1.4 passing through zero, suggesting the presence of scalemic and close to racemic mixtures, since enantiomerically pure natural constituents showed positive or negative specific rotations greater than 10 units.

Chemical Composition, Antioxidant, Antimicrobial and Insecticidal Activities of Essential Oil from a Moroccan Endemic Plant: Bubonium imbricatum.[Pubmed:30475515]

Nat Prod Commun. 2016 Nov;11(11):1717-1720.

The chemical composition, antioxidant, antimicrobial and insecticidal properties of essential oil obtained by hydro-distillation from Bubonium imbricatum Cav. have been investigated. The essential oil of aerial parts was analyzed by GC-FID and GC-MS. A total of 63 compounds were identified representing more than 82% of the oil. The major components were cis-chrysanthenyl acetate (31.2%) and Thymol isobutyrate (3.4%). The antioxidant activity was evaluated by the DPPH and reducing power test. The data showed moderate activity compared with the reference compounds. Our results showed strong activity of the investigated oil against all tested microorganisms. The highest antibacterial activity was observed against Bacillus subtilis (inhibition zone= 18 +/- 0.21, MIC= 0.18 mg/mL). In general, Gram-positive bacteria were more susceptible than Gram-negative ones. Candida parapsilosis was the most sensitive among the Candida strains tested. LD50 and LD90 values were 33.1 and 53.1 ppm against 1-d-old larvae of Aedes aegypti L.

Antidiarrheal Thymol Derivatives from Ageratina glabrata. Structure and Absolute Configuration of 10-Benzoyloxy-8,9-epoxy-6-hydroxythymol Isobutyrate.[Pubmed:27626392]

Molecules. 2016 Sep 12;21(9). pii: molecules21091132.

Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-benzoyloxy-8,9-dehydro-6-hydroxyThymol isobutyrate (4), 10-benzoyloxy-8,9-dehydrothymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryl-oxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxyThymol isobutyrate (1), together with other two already known thymol derivatives identified as 10-benzoyloxy-8,9-epoxy-6-methoxyThymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxyThymol isobutyrate (3) were also obtained. In this paper, we report the structures and complete assignments of the (1)H and (13)C-NMR data of compounds 1-7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity comparable to emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation to anti-propulsive effect, compound 1 and 1a showed inhibitory activity, with activities comparable to quercetin and compound 9, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata.

Chemical composition and biological activity of Pulicaria vulgaris essential oil from Iran.[Pubmed:25532299]

Nat Prod Commun. 2014 Nov;9(11):1633-6.

The present study investigated the chemical composition of the essential oil (EO) from aerial parts (flowering stage) of Pulicaria vulgaris Gaertn. by GC-MS. Also, the antimicrobial activity of the EO against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi (Aspergillus niger and Candida albicans) was tested. In total, 23 compounds were recognized, accounting for 98.08% of the EO. The main compounds in the EO were thymol (50.22%), p-menth-6-en-2-one (carvotanacetone, 20.2%), Thymol isobutyrate (16.88%), menthan-2-one (4.31%), 1-methyl-1,2-propanedione (4.13%), 2,5-dimethoxy-p-cymene (4.01%), myrtenol (1.22%), linalool (1.1%), and beta-myrcene (1.9%). Results of antibacterial test of P. vulgaris essential oil showed that all assayed concentrations significantly inhibited the growth of B. cereus, S. aureus, E. coli, and P. aeruginosa at P < 0.05. MIC for B. cereus, S. aureus, E. coli, P. aeruginosa was 17.5, 25.2, 19.4 and 33.2 mug/mL respectively; antifungal screening of the essential oil of P. vulgaris showed that the oil significantly inhibited the growth of A. niger and C. albicans (MIC = 15.5 and 9.9 mug/mL, respectively). Results of cytotoxicity assay showed that the essential oil exhibited a significant cytotoxic activity against both cell lines. In case of MCF-7 and Hep-G2 cell lines, IC50 of the essential oil were 5.36 and 7.16 mug/ml, respectively. The potent antimicrobial and cytotoxic activities of the EO may be attributed to its high contents of thymol, carvotanacetone and Thymol isobutyrate. Antimicrobial and antitumor chemotherapies are showing diminishing effectiveness because of emergence of drug-resistance. Hence, using efficient natural chemotherapeutic agents such as Pulicaria vulgaris essential oil with fewer side effects is an encouraging approach to fight cancer and infectious diseases in medicine, agriculture, food science and related fields.

Structure, absolute configuration, and antidiarrheal activity of a thymol derivative from Ageratina cylindrica.[Pubmed:24502360]

J Nat Prod. 2014 Feb 28;77(2):358-63.

The leaves of Ageratina cylindrica afforded a thymol derivative that was characterized by physical and spectroscopical methods as (8S)-8,9-epoxy-6-hydroxy-l0-benzoyloxy-7-oxoThymol isobutyrate (1). The absolute configuration of 1 was established as 8S by vibrational circular dichroism spectroscopy in combination with density functional theory calculations and by evaluation of the Flack and Hooft X-ray parameters. Compound 1 showed weak antiprotozoal activity against Entamoeba histolytica and Giardia lamblia trophozoites and a high inhibitory effect on hyperpropulsive movement of the small intestine in rats.

Chemical composition of essential oils from a multiple shoot culture of Telekia speciosa and different plant organs.[Pubmed:22799093]

Nat Prod Commun. 2012 May;7(5):625-8.

The composition of essential oil from Telekia speciosa leaves, flowers, roots, stems and in vitro regenerated shoots was studied by GC-MS-FID leading to the determination of 112 compounds. The qualitative composition of the essential oil from the examined plant material was similar, whereas quantities of individual components of the oils varied widely depending on the kind of plant material. The most striking differences were observed between the oils produced by aerial and underground parts of the intact plant, as well as between oils produced by in vitro grown shoots and leaves of the intact plant. The main volatiles of leaf essential oil were: (E,E)-famesol (21.2%) and (E)-nerolidol (17.9%), while isoalantolactone was the predominant component of the root (62.3%) and flower oils (23.0%). Numerous thymol derivatives were also found, among them 10-isobutyryloxy-8,9-epoxyThymol isobutyrate, which was one of the main components found in the flower oil (20.5%) and that from the in vitro cultures (20.2%).

Cytotoxic and anti-infective phenolic compounds isolated from Mikania decora and Cremastosperma microcarpum.[Pubmed:21472652]

Planta Med. 2011 Sep;77(14):1597-9.

An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxyThymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (+/-)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes.

Antimicrobial activity of 10-isobutyryloxy-8,9-epoxythymol isobutyrate.[Pubmed:16242268]

Fitoterapia. 2005 Dec;76(7-8):687-90.

10-Isobutyryloxy-8,9-epoxyThymol isobutyrate was found to be a major constituent of Inula helenium and Inula royleana root cultures. The compound showed moderate antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Escherischia coli, Pseudomonas aeruginosa and Candida albicans.

Thymol derivatives from a root culture of Inula helenium.[Pubmed:15813387]

Z Naturforsch C J Biosci. 2004 Jul-Aug;59(7-8):606-8.

A root culture of Inula helenium L. was established from leaf explants of aseptic seedlings. An ethanol extract from the lyophilised roots was fractionated using different chromatographic techniques (CC, TLC). The main secondary metabolites found in the root culture were two thymol derivatives: 10-isobutyryloxy-8,9-epoxy-Thymol isobutyrate (1) and 10-isobutyryloxy-6-methoxy-8,9-epoxy-Thymol isobutyrate (2). The compounds were identified by spectral methods. Quantification of compound 1 in plant material was done by analytical RP-HPLC.