Carvone Derivatives Research Articles

MOLECULAR DOCKING PREDICTION OF CARVONE TOWARDS GABA-ATASE AND SODIUM CHANNEL

Aim: Modern tool designs frequently employ molecular docking to anticipate small molecules’ binding orientation and better comprehend drug-receptor interactions. Carvone’s molecular docking analysis against sodium channels and GABA-AT is part of this research investigation.
 Introduction: Carvone’s molecular docking analysis against sodium channels and GABA-AT is part of this research investigation. The biological significance of carvone has been demonstrated to include anti-epileptic, anti-fungal, anti-inflammatory, anti-cancer, and antioxidant effects. In modern drug design, molecular docking is commonly used to get an understanding of drug-receptor interaction carried out an in-silico evaluation of derivatives of carvone.
 Methodology: ChemDraw 2D (15.1) software is used to draw the ligands, ChemDraw-3D is utilized to decrease energy consumption, chimera is used to produce the protein, and Auto Dock 4.0 was used to examine the binding score. To determine whether it would cross to BBB+/BBB- or not, cheminformatics and fingerprint analysis were done using Molinspiration and Adaboost with SVM.
 Result: Comparable metrics for newly created carvone derivatives included potential energy, docking score, glide score, and highest docking score. Compounds with docking scores of (-8.39, -5.06, -4.00 kcal/mol). The conformers at the active site are shown and predicted using Discovery Studio Visualizer.
 Conclusion: The results of the molecular docking study showed that compound1 has a high affinity for the active pocket and a low binding energy, which made them potentially useful as an anti-convulsant.

Synthesis of Carvone Derivatives and In Silico and In Vitro Screening of Anti-Inflammatory Activity in Murine Macrophages.

The chemical modification of natural compounds is a promising strategy to improve their frequently poor bioavailability and low potency. This study aimed at synthesizing chemical derivatives of carvone, a natural monoterpene with anti-inflammatory properties, which we recently identified, and evaluating their potential anti-inflammatory activity. Fourteen chemical derivatives of carvone were synthesized, purified and their chemical structures confirmed. Noncytotoxic concentrations of the test compounds were selected based on the resazurin reduction assay. Among the tested compounds, four significantly reduced the lipopolysaccharides-induced protein levels of the inducible isoform of the nitric oxide synthase and nitric oxide production and showed a dual effect on pro-IL-1 protein levels in the Raw 264.7 cell line. The Ligand Express drug discovery platform was used to predict the targets of the test compounds, and an enrichment analysis was performed to group the different biological processes and molecular and cellular functions of the tested compounds. Moreover, Ligand Express also predicted that all chemicals evaluated have intestinal and blood-brain barrier permeability, do not inhibit P-gp and do not interact with major receptors. Although presenting anti-inflammatory and some advantageous ADME properties, the tested compounds still have low potency and specificity but may provide novel structures the further chemical modification of which may yield more promising drugs.

Some unusual transformations of a highly reactive α-bromocaranone

The facile synthesis of a highly reactive α-bromocaranone from (+)-carene is reported. This intermediate was found to generate diverse chiral building blocks through radical or carbocation mediated cyclopropyl fragmentation reactions in moderate to excellent yields. Furthermore, the formation of an unexpected carvone derivative prompted several control studies that provided mechanistic insight into an unusual transformation. This study not only demonstrates the synthesis of a variety of chiral building blocks but provides insight into the reactivity of keto-halo-cyclopropanes in general.

Design, Synthesis, Crystal Structure, and Fungicidal Activity of L-Carvone Derivatives Containing an Oxime Ester Moiety

Design, Synthesis, Crystal Structure, and Fungicidal Activity of <i>L</i>-Carvone Derivatives Containing an Oxime Ester Moiety

Novel (‒)-carvone derivatives as potential anticonvulsant and analgesic agents

Novel hydrazones based on (‒)-carvone were synthesized via condensation of terpenoid with 4-R-phenoxyacetic acid hydrazides. The structure of target compounds was established by FT-IR, Raman, 1H-NMR and 13C-NMR spectral analysis, FAB/ESI mass spectrometry. (‒)-Carvone hydrazones were proven to exist as Z/E geometrical isomers about C = N bond using ion mobility-tandem mass spectrometry (IM-MS/MS). Single crystal X-ray diffraction study was applied to determine molecular and crystal structure of compound 3e. Hydrazones 3a-3e were evaluated as potential anticonvulsant agents after their oral administration against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures in mice. Analgesic activity of compounds was investigated by topical application on models of capsaicin and AITC-induced pain. The present findings indicate that (‒)-carvone derivatives afforded seizure protection both at short (1 h) and long (24 h) time period by blocking electroshock- and chemical-induced convulsions. Hydrazones binding to TRPA1/TRPV1 ion channels was proposed as possible mechanism explaining significant analgesic effect of compounds.

C3 and C6 Modification-Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones.

The scope for biocatalytic modification of non‐native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non‐native terpenone‐derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues of R‐(−)‐carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio‐substitution and the substrate diastereomer. Bioreduction of (−)‐carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)‐Me and (6R)‐Me substituted (−)‐carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer–Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non‐native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)‐dihydrocarvone Baeyer–Villigerase expansion. Optimum enzymatic reactions were scaled up to 60–100 mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold‐modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single‐isomer chiral polymer feedstocks.

In silico study of carvone derivatives as potential neuraminidase inhibitors

Recent outbreaks of highly pathogenic influenza strains have highlighted the need to develop new anti-influenza drugs. Here, we report an in silico study of carvone derivatives to analyze their binding modes with neuraminidase (NA) active sites. Two proposed carvone analogues, CV(A) and CV(B), with 36 designed ligands were predicted to inhibit NA (PDB ID: 3TI6) using molecular docking. The design is based on structural resemblance with the commercial inhibitor, oseltamivir (OTV), ligand polarity, and amino acid residues in the NA active sites. Docking simulations revealed that ligand A18 has the lowest energy binding (∆Gbind) value of -8.30kcal mol-1, comparable to OTV with ∆Gbind of -8.72kcal mol-1. A18 formed seven hydrogen bonds (H-bonds) at residues Arg292, Arg371, Asp151, Trp178, Glu227, and Tyr406, while eight H-bonds were formed by OTV with amino acids Arg118, Arg292, Arg371, Glu119, Asp151, and Arg152. Molecular dynamics (MD) simulation was conducted to compare the stability between ligand A18 and OTV with NA. Our simulation study showed that the A18-NA complex is as stable as the OTV-NA complex during the MD simulation of 50ns through the analysis of RMSD, RMSF, total energy, hydrogen bonding, and MM/PBSA free energy calculations.

Preparation of cis-γ-hydroxycarvone derivatives for synthesis of sesterterpenoid natural products: total synthesis of phorbin A.

A robust synthetic approach to cis-γ-hydroxycarvone derivatives has been developed, enabling efficient access to synthetic building blocks for the growing family of bioactive sesterterpenoid natural products. Using this approach, an allyl bromide carvone derivative was used as the key building block for the total synthesis of the natural product phorbin A. This synthetic sequence also demonstrates the utility of benozyl enol ethers as an effective means of masking a β-ketophosphonate and their subsequent application in a one-pot benzoyl transfer-intramolecular Horner-Wadsworth-Emmons reaction.

ChemInform Abstract: Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile.

ChemInform Abstract: Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile.

Rapid Access to the Heterocyclic Core of the Calyciphylline A and Daphnicyclidin A-Type Daphniphyllum Alkaloids via Tandem Cyclization of a Neutral Aminyl Radical

A streamlined approach to the tertiary amine-containing core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids is presented. A known carvone derivative is converted into the core structure in only four synthetic operations, and it is well poised for further elaboration. The key enabling methodology is a radical cyclization cascade beginning with addition of a secondary, neutral aminyl radical to the β-position of an enone, followed by trapping with a pendant alkyne.

Acaricidal Activities against House Dust Mites of Spearmint Oil and Its Constituents

The aim of this study was to evaluate the acaricidal activities of spearmint oil and carvone derivatives against house dust mites using contact and fumigant toxicity bioassays to replace benzyl benzoate as a synthetic acaricide. Based on the LD50 values, the contact toxicity bioassay revealed that dihydrocarvone (0.95 and 0.88 µg/cm2) was 7.7 and 6.8 times more toxic than benzyl benzoate (7.33 and 6.01 µg/cm2) against Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively, followed by carvone (3.78 and 3.23 µg/cm2), spearmint oil (5.16 and 4.64 µg/cm2), carveol (6.00 and 5.80 µg/cm2), and dihydrocarveol (8.23 and 7.10 µg/cm2). Results of the fumigant toxicity bioassay showed that dihydrocarvone (2.73 and 2.16 µg/cm2) was approximately 4.0 and 4.8 times more effective than benzyl benzoate (11.00 and 10.27 µg/cm2), followed by carvone (6.63 and 5.78 µg/cm2), carveol (7.58 and 7.24 µg/cm2), spearmint oil (9.55 and 8.10 µg/cm2), and dihydrocarveol (9.79 and 8.14 µg/cm2). Taken together, spearmint oil and carvone derivatives are a likely viable alternative to synthetic acaricides for managing house dust mites.

Enantiospecific Total Synthesis of N‐Methylwelwitindolinone D Isonitrile

The total synthesis of N-methylwelwitindolinone D isonitrile (1) has been achieved in 17 steps from a readily available carvone derivative. The route features a double C-H functionalization event involving a keto oxindole substrate to introduce the tetrahydrofuran ring of the natural product.

Rapid Construction of the ABC Ring System in the Daphniphyllum Alkaloid Daphniyunnine C

An efficient and scalable synthesis of the ABC ring system common to the calyciphylline A-type alkaloids has been developed. The tricyclic core of the alkaloids features a bowl-shaped [6-6-5] skeleton with five stereogenic centers including an all-carbon quaternary center. It was constructed rapidly from a readily available carvone derivative through a seven-step sequence involving an aza-Michael addition and Pd-catalyzed enolate α-vinylation as key steps.

Synthesis of (R)-(–)-Carvone Derivatives

(R)-(-)-Carvone, the main constituent of spearmint oil, has several synthetic applications and is used in cosmetics, food, and pharmaceutical preparations. In a recent study we demonstrated that (R)-(-)-carvone shows significant analgesic activity. In the present report, (R)-(-)-carvone derivatives which have pharmacological potential are described. These compounds can be used in studies of structure-activity relationship to develop novel drugs.

ChemInform Abstract: Halogenated Terpenoids. Part 28. The Conversion of Limonene Tetrabromide (I) into Carvone Derivatives with Retained C8 Stereochemistry.

ChemInform Abstract: Halogenated Terpenoids. Part 28. The Conversion of Limonene Tetrabromide (I) into Carvone Derivatives with Retained C8 Stereochemistry.

Regioselective Hydration and Deprotection of Chiral, Dissymmetric Iminodinitriles in the Scope of an Asymmetric Strecker Strategy

AbstractThe controlled, selective decomposition of dissymmetric iminodinitriles (DIDN) of formula RCH(CN)–NH–C(CN)R′R″ (considered as N‐protected alpha‐aminonitriles), is a critical issue for an original asymmetric Strecker strategy previously outlined by us for the enantioselective synthesis of amino acids. This strategy, derived from Harada's work, involves a double sequence of (i) stereoselective Strecker condensation of a chiral ketone R′R″CO with NH3 and HCN, followed by (ii) stereoselective Strecker condensation with an aldehyde RCHO and HCN, then (iii) regioselective retro‐Strecker decomposition of the DIDN intermediate to release the target alpha‐aminonitrile. In addition to the use of quite simple, cheap cyclic ketones (e.g. carvone derivatives) as chiral auxiliaries, another great advantage of this strategy is that step (iii) enables the recovery of the chiral ketone and hence its reuse. While our previous investigations on step (iii) under various conditions, either preceded or followed by the hydration of the secondary nitrile group RH(CN)‐ into an amide, had shown insufficient selectivity, we succeeded in the regioselective hydration of the secondary nitrile of DIDN without significant racemisation, by using a large excess of hydrogen peroxide in methanolic/aqueous ammonia (pH 12.5) at low temperature. The resulting imino nitrile/amide compound was then classically decomposed in acidic medium through a retro‐Strecker reaction, affording the chiral alpha‐amino amide. Alternately, the regioselective retro‐Strecker decomposition of the tertiary moiety of the DIDN was achieved by reaction with silver cation in aqueous nitric acid, also without significant racemisation, thus establishing an original, enantioselective synthesis of alpha‐aminonitriles. In both reactions, the chiral ketonic auxiliary resulting from DIDN decomposition was recovered in good yields. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)

Sensitivity of photoelectron circular dichroism to structure and electron dynamics in the photoionization of carvone and related chiral monocyclic terpenone enantiomers

The photoelectron circular dichroism that arises in the angular distribution of photoelectrons emitted from the carbonyl group in randomly oriented pure enantiomers of carvone, and a number of carvone derivatives, is investigated by continuum multiple scattering calculations. Core ionization of carbonyl C 1s orbitals is examined for six different isopropenyl tail conformations of carvone. These show clear differences of behavior both between axial and equatorial conformations, and between the three rotational conformers of each. The pronounced dependence of the dichroism on orientation of a tail grouping, itself remote from the localized initial C 1s site, indicates the presence of long range final state photoelectron scattering effects. Analogous data for the outermost valence orbital, partially localized on the carbonyl group, are also presented. The apparently enhanced sensitivity of the dichroism exhibited in this work is discussed in terms of the particular dependence on photoelectron interference effects that is probed by the dichroism measurement and is contrasted with the usual beta parameter and cross section determinations.

Cp2TiCl‐Promoted Isomerization of Trisubstituted Epoxides to exo‐Methylene Allylic Alcohols on Carvone Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cp2TiCl-promoted isomerization of trisubstituted epoxides to exo-methylene allylic alcohols on carvone derivatives.

The ring-opening reaction of trisubstituted epoxides promoted by Cp2TiCl led to exo-methylene allylic alcohols as major compounds when 0.5 M solutions of the epoxides were added to 0.1 M solutions of the reagent at room temperature in THF. In most cases, the allylic alcohols were contaminated with saturated alcohols. Normal and reverse addition modes led to the alternate product being favored. The different stereochemical outcome of cis- and trans-epoxy acetates is rationalized in terms of mechanistically biased elimination processes.

ChemInform Abstract: Water‐Soluble Constituents of Caraway: Carvone Derivatives and Their Glucosides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.