Synthesis of a new nitrogenated drimane derivative with antifungal activity

Zárraga, Miguel; Zárraga, Ana María; Rodríguez, Bárbara; Pérez, Claudia; Paz, Cristian; Paz, Pablo; Sanhueza, Carlos

doi:10.1016/j.tetlet.2008.05.092

Cited by 19 publications

(10 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…21,22 Drimenol can also be used as starting compound for (-)-ambrox, the most important equivalent of Ambergris, widely used in perfumery. 23,24 Additionally, it has been the starting material for nitrogenated drimane with guanidine moiety possessing antifungal activity 25 and the cytotoxic ent-cyclozonarone especially towards MS-1, mice endothelial cells. 26 These selected examples illustrate the importance of this secondary metabolite and moreover the necessity to identify new natural sources for this compound due to the restricted occurrence of D. winteri.…”

Section: Essential Oil Compositionmentioning

confidence: 99%

Chemical characterization of essential oils from Drimys angustifolia miers (Winteraceae) and antibacterial activity of their major compounds

Santos¹,

Dognini²,

Begnini³

et al. 2013

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

Nos últimos anos, os óleos essenciais vêm sendo intensamente estudados como fonte natural de novos agentes antimicrobianos. Neste trabalho, os óleos essenciais das folhas e galhos de Drimys angustifolia do sul do Brasil foram obtidos por hidrodestilação e analisados por cromatografias gasosas com detector de ionização de chama (GC-FID) e com espectrômetro de massa (GC-MS). Os constituintes drimenol e biciclogermacreno foram isolados por cromatografia em coluna do óleo essencial dos galhos e folhas, respectivamente. Os óleos, os constituintes isolados e combinações destes foram testados contra bactérias Gram-(+) e Gram-(-). Os óleos essenciais foram mais ativos contra Bacillus cereus, com MIC (concentração inibitória mínima) de 125 e 250 µg mL -1 para os galhos e folhas, respectivamente, inibindo fortemente o crescimento bacteriano. Biciclogermacreno foi mais ativo que drimenol, fornecendo um valor de MIC de 167 µg mL -1 contra B. cereus. Não foi observado qualquer efeito sinérgico nas combinações testadas.Essential oils have been extensively studied in recent years as a natural source of new antimicrobial agents. In this work, essential oils of leaf and branch from Drimys angustifolia growing in Southern Brazil were obtained by hydrodistillation and analyzed by gas chromatographies with flame ionization detector (GC-FID) and with mass spectrometer (GC-MS). Drimenol and bicyclogermacrene were isolated by column chromatography from branch and leaf essential oils, respectively. Oils, isolated compounds and combinations of them were assayed against Gram-(+) and Gram-(-) bacteria. The oils showed to be more active against Bacillus cereus, with minimum inhibitory concentration (MIC) 125 and 250 µg mL -1 for branch and leaf oils, respectively, strongly inhibiting bacterial growth. Bicyclogermacrene was more active then drimenol, providing a MIC value of 167 µg mL -1 against B. cereus. Synergism was not observed in any of the combinations tested.

show abstract

Section: Essential Oil Compositionmentioning

confidence: 99%

Chemical characterization of essential oils from Drimys angustifolia miers (Winteraceae) and antibacterial activity of their major compounds

Santos¹,

Dognini²,

Begnini³

et al. 2013

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…Lately, interest has grown for nitrogenated drimane derivatives in the search of compounds with antifungal activity. Thus Zárraga et.al decided to attempt the synthesis of a new nitrogenated derivative starting from (-)-drimenol [36], and found that by binding functional groups at C-11, the antifungal activity increased.…”

Section: Drimenol As Natural Chiral Synthon For Other Drimane Terpenomentioning

confidence: 99%

“…Vlad et al [37] prepared 11-aminodrim-7-ene (64) from drimenol in four steps, in an attempt to improve the previous reported synthesis [36], although (-)-drimenol in this case was synthesized as described before [14]. Synthetic (-)-drimenol was transformed in drimenal oxime 63, exactly by the same procedure reported before [36]. Oxime 63 was then transformed into nitrile 66, which was refluxed with LiAlH 4 to provide 64 in 50% yield (Figure 25).…”

Section: Drimenol As Natural Chiral Synthon For Other Drimane Terpenomentioning

confidence: 99%

Drimenol: A Versatile Synthon for Compounds with trans-Drimane Skeleton

Cortés

Delgado

Saitz

et al. 2011

Natural Product Communications

View full text Add to dashboard Cite

Several reviews have been published on sesquiterpenes, and on drimane-type sesquiterpenes, going through drimenol and related compounds among others. However, to our knowledge, this is the first review exclusively on drimenol. Although, the main focus is on drimenol as a synthon for other drimane-type compounds, synthetic routes to obtain racemic and (-)-drimenol are summarized, as well as its isolation and determination of its configuration, in the early fifties. The reviewed synthetic routes start from natural (-)-drimenol as chiral synthon in most of cases, nevertheless total syntheses are considered as well. The strategies where racemic drimenol is involved begin with biomimetic cyclization of trans-farnesol. Microbiological procedures to functionalize the A ring of drimenol are also commented. The revision is classified according to the chemical structure of the final product, which mainly correspond to structures of natural occurrence, although other related derivatives are also analyzed.

show abstract

“…For example, bioactive sesquiterpene lactones such as cinnamolide and drimenin have been isolated from this source showing potent inhibitory activity against the human α4β2 nicotinic acetylcholine receptors that are involved in drug addiction [14]. Also, alcohols such as drimendiol have shown antibacterial quorum sensing activity [15,16] and they have been used as a scaffold for the hemisynthesis of nitrogenated derivatives with antifungal activity against Candida albicans [17]. In this work, we aim at obtaining novel drimane sesquiterpenoids from the partial oxidation of isodrimeninol (C1) isolated from barks of Drimys winteri.…”

Section: Introductionmentioning

confidence: 99%

Oxidation of Isodrimeninol with PCC Yields Drimane Derivatives with Activity against Candida Yeast by Inhibition of Lanosterol 14-Alpha Demethylase

et al. 2020

Self Cite

View full text Add to dashboard Cite

Candida species cause an opportunistic yeast infection called Candidiasis, which is responsible for more than 50,000 deaths every year around the world. Effective treatments against candidiasis caused by non-albicans Candida species such as C. glabrata, C. parapsilosis, C. aureus, and C. krusei are limited due to severe resistance to conventional antifungal drugs. Natural drimane sesquiterpenoids have shown promising antifungal properties against Candida yeast and have emerged as valuable candidates for developing new candidiasis therapies. In this work, we isolated isodrimeninol (C1) from barks of Drimys winteri and used it as starting material for the hemi-synthesis of four sesquiterpenoids by oxidation with pyridinium chlorochromate (PCC). The structure of the products (C2, C3, C4, and C5) was elucidated by 1D and 2D NMR spectroscopy resulting in C4 being a novel compound. Antifungal activity assays against C. albicans, C. glabrata, and C. krusei revealed that C4 exhibited an increased activity (IC50 of 75 μg/mL) compared to C1 (IC50 of 125 μg/mL) in all yeast strains. The antifungal activity of C1 and C4 was rationalized in terms of their capability to inhibit lanosterol 14-alpha demethylase using molecular docking, molecular dynamics simulations, and MM/GBSA binding free energy calculations. In silico analysis revealed that C1 and C4 bind to the outermost region of the catalytic site of 14-alpha demethylase and block the entrance of lanosterol (LAN) to the catalytic pocket. Binding free energy estimates suggested that C4 forms a more stable complex with the enzyme than C1, in agreement with the experimental evidence. Based on this new approach it is possible to design new drimane-type sesquiterpenoids for the control of Candida species as inhibitors of 14-alpha demethylase.

show abstract

Synthesis of a new nitrogenated drimane derivative with antifungal activity

Cited by 19 publications

References 12 publications

Chemical characterization of essential oils from Drimys angustifolia miers (Winteraceae) and antibacterial activity of their major compounds

Chemical characterization of essential oils from Drimys angustifolia miers (Winteraceae) and antibacterial activity of their major compounds

Drimenol: A Versatile Synthon for Compounds with trans-Drimane Skeleton

Oxidation of Isodrimeninol with PCC Yields Drimane Derivatives with Activity against Candida Yeast by Inhibition of Lanosterol 14-Alpha Demethylase

Contact Info

Product

Resources

About