Phytochemical Composition of Commiphora Oleogum Resins and Their Cytotoxicity against Skin Cancer Cells.

Oleogum resins of the genus Commiphora have been used in traditional medicines for centuries. More than 200 Commiphora species exhibit highly variable phytochemical compositions. A novel highly selective, sensitive, accurate HPLC-MS/MS method was developed and validated to quantify five characteristic phytosteroids and furanosesquiterpenoids, namely (E)-guggulsterone, (Z)-guggulsterone, curzerenone, furanoeudesma-1,3-diene, and myrrhone. The resulting contents and additionally GC analysis were used to classify and differentiate Commiphora oleogum resins of the species C. myrrha, C. erythraea, C. mukul, C. holtziana, C. confusa, and C. kua, as well as unspecified resins. Interestingly, a Commiphora sample from Ogaden, Ethiopia, comprised 446 ng/mg guggulsterones presumed to be unique to C. mukul from the Indian subcontinent. However, Commiphora from Ogaden differed considerably from C. mukul in respect to guggulsterones isomer's ratio. Moreover, the cytotoxicity of Commiphora extracts, essential oils, botanical drugs containing Commiphora, and pure compounds against the epidermoid carcinoma A431, malignant melanoma RPMI-7951 and SK-MEL-28 cells was investigated in vitro. Thereby, especially C. mukul extract and C. myrrha essential oil exhibited high cytotoxicity against skin cancer cells with IC50 of 2.9-10.9 µg/mL, but were less toxic to normal keratinocytes. In summary, Commiphora oleogum resins and its phytochemicals warrant further investigation aiming at chemotaxonomical classification as well as application in skin cancer treatment.

Effect of the Chromone Core Substitution of Dirchromone on the Resultant Biological Activities.

Dirchromone is a bioactive vinyl sulfoxide-bearing chromone first isolated from the shrub Dirca palustris. Altogether, 32 of its derivatives were prepared to assess the effect of substitution of its chromone core upon activities against cancer cell lines, Gram-positive bacteria, and fungi (such as Candida albicans). All compounds were synthesized following a synthetic strategy involving Pummerer and soft-enolization Baker-Venkataraman rearrangements. Substituent position changes induced little variability on the activities tested. There was no correlation between cytotoxic and antibacterial effects, suggesting different underlying mechanisms of action. In particular, hydroxy group and cyanide substituents diminished cytotoxicity, with the latter featuring enhanced antibacterial activity. Higher homologues of 6-alkoxydirchromones also exhibited progressively emerging antifungal activity. Other modifications had moderate effects on cytotoxicity with some derivatives leading to increased potency. This behavior highlights the robustness of the natural dirchromone pharmacophore toward decoration, thus paving the way for more elaborate future drug design.

Essential Oils from Bolivia. XV. Herzogole, an Original Monoterpene Benzodioxole from an Essential Oil from Pentacalia herzogii (Cabrera) Cuatrec.

Over 15 years, with the support of a Canadian funding agency, the Universidad Mayor de San Simón, in Bolivia, undertook a large survey of aromatic plants of the South American country. More than a hundred species were studied under various aspects, including the production and characterization of essential oils. As part of this survey, the chemical composition of an essential oil sample obtained from Pentacalia herzogii (Asteraceae) growing wild in the High Valley region of the department of Cochabamba was determined by a combination of GC and GC-MS measurements. α-Pinene was the main constituent of this essential oil (34%), accompanied by limonene (22%) and germacrene D (7.5%) as well as an important fraction of methoxylated monoterpenoids. They were mainly isomers of thymol methyl ether, accounting for 13% of the chromatogram. A new quantitatively important compound (9%) was identified through NMR and chemical synthesis as 4-isopropyl-6-methylbenzo[d][1,3]dioxole, and designated herzogole, alongside the minor related compound 1-isopropyl-2,3-dimethoxy-5-methylbenzene. The monoterpene benzodioxole featured a distinctive green-phenolic aroma which could raise interest for fragrance use. Since these compounds were not known naturally, a biosynthetic mechanism of their formation was proposed and put in perspective to illustrate the metabolic originality of P. herzogii.

The Biological Activity of Monarda didyma L. Essential Oil and Its Effect as a Diet Supplement in Mice and Broiler Chicken.

The use of growth-promoting antibiotics in livestock faces increasing scrutiny and opposition due to concerns about the increased occurrence of antibiotic-resistant bacteria. Alternative solutions are being sought, and plants of Lamiaceae may provide an alternative to synthetic antibiotics in animal nutrition. In this study, we extracted essential oil from Monarda didyma, a member of the Lamiaceae family. We examined the chemical composition of the essential oil and then evaluated the antibacterial, antioxidant, and anti-inflammatory activities of M. didyma essential oil and its main compounds in vitro. We then evaluated the effectiveness of M. didyma essential oil in regard to growth performance, feed efficiency, and mortality in both mice and broilers. Carvacrol (49.03%) was the dominant compound in the essential oil extracts. M. didyma essential oil demonstrated antibacterial properties against Escherichia coli (MIC = 87 µg·mL-1), Staphylococcus aureus (MIC = 47 µg·mL-1), and Clostridium perfringens (MIC = 35 µg·mL-1). Supplementing the diet of mice with essential oil at a concentration of 0.1% significantly increased body weight (+5.4%) and feed efficiency (+18.85%). In broilers, M. didyma essential oil significantly improved body weight gain (2.64%). Our results suggest that adding M. didyma essential oil to the diet of broilers offers a potential substitute for antibiotic growth promoters.

11-Keto-α-Boswellic Acid, a Novel Triterpenoid from Boswellia spp. with Chemotaxonomic Potential and Antitumor Activity against Triple-Negative Breast Cancer Cells.

Boswellic acids, and particularly 11-keto-boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and potential antitumor efficacy. Although boswellic acids generally occur as α-isomers (oleanane type) and ß-isomers (ursane type), 11-keto-boswellic acid (KBA) was found only as the ß-isomer, ß-KBA. Here, the existence and natural occurrence of the respective α-isomer, 11-keto-α-boswellic acid (α-KBA), is demonstrated for the first time. Initially, α-KBA was synthesized and characterized by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy, and a highly selective, sensitive, and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed by Design of Experiments (DoE) using a pentafluorophenyl stationary phase. This method allowed the selective quantification of individual 11-keto-boswellic acids and provided evidence for α-KBA in Boswellia spp. oleogum resins. The contents of α-KBA as well as further boswellic acids and the composition of essential oils were used to chemotaxonomically classify 41 Boswellia oleogum resins from 9 different species. Moreover, α-KBA exhibited cytotoxicity against three treatment-resistant triple-negative breast cancer (TNBC) cell lines in vitro and also induced apoptosis in MDA-MB-231 xenografts in vivo. The respective ß-isomer and the acetylated form demonstrate higher cytotoxic efficacies against TNBC cells. This provides further insights into the structure-activity relationship of boswellic acids and could support future developments of potential anti-inflammatory and antitumor drugs.

On the role of the vinylsulfoxide side chain of dirchromone towards its bioactivities.

Analogs of dirchromone were prepared to shed light on the pivotal role of its peculiar vinylsulfoxide side chain towards its cytotoxic and antimicrobial properties, especially dependant upon the presence and oxidation state of sulfur. The reaction of dirchromone with cysteamine revealed a surprising Michael acceptor behavior with elimination of the methylsulfinyl moiety and redox transformation of the sulfur atom that could be involved in the mode of action of dirchromone within cells.

Pili Tree (Canarium ovatum) Resin's Antibacterial Essential Oil and Hydrosol as Rich Sources of (S)-Phellandrenes Derivatives.

Five batches of resin from the Pili tree (Canarium ovatum Engl.) were distilled, and their essential oils and hydrosols were analyzed by gas chromatography. The oils, obtained in yields of 13.4-19.7 % v/m, featured α-phellandrene in high proportions (50-65 %), alongside limonene, ß-phellandrene and para-cymene. Chiral GC analysis confirmed that both phellandrenes were in fact >95 % (S)-(+) enantiomers, while the other monoterpenes featured less pronounced enantiomeric excesses. The hydrosols were rich in α-phellandrene oxidation products including cis-α-phellandrene epoxide and a series of para-menth-5-ene-1,2-diol isomers. Both essential oils and hydrosols were tested for their antibacterial activity against Escherichia coli and Staphylococcus aureus and exhibited MIC90 of less than 5 and 0.5 mg/mL of total volatiles, respectively. The essential oil features some potential as a source of readily available natural (S)-(+)-α-phellandrene.

Soft-enolization Baker-Venkataraman Rearrangement Enabled Total Synthesis of Dirchromones and Related 2-Substituted Chromones.

A seven-step total synthesis of the original scaffold of cytotoxic dirchromones involving an unprecedented soft-enolization Baker-Venkataraman rearrangement was designed. The methodology enabled access to naturally occurring dirchromone 1 (21% overall yield) at gram-scale, which was screened for cytotoxicity against 13 cancer cell lines. The scope of the soft-enolization Baker-Venkataraman rearrangement encompasses diversely substituted dirchromones, including flavonoids, 2-styrylchromones, and 2-phenylethylchromones.

Antimalarial Activities of Alkyl Cyclohexenone Derivatives Isolated from the Leaves of Poupartia borbonica.

Bioactivity-guided fractionation of the ethyl acetate extract of the leaves of Poupartia borbonica led to the isolation of three new alkyl cyclohexenone derivatives 1-3, and named Poupartone A-C. The structures of the new compounds were elucidated by 1D and 2D NMR spectroscopic data analysis and MS, whereas calculated and experimental ECD spectra were used to define the absolute configurations. These compounds were active against 3D7 and W2 Plasmodium falciparum strains with IC50 values between 0.55 and 1.81 µM. In vitro cytotoxicity against WI38 human fibroblasts and the human cervical cancer cell line HeLa (WST-1 assay) showed that these compounds were also cytotoxic, but no hemolytic activity was observed for the extract and pure compounds. An in vivo antimalarial assay was performed on the major cyclohexenone using P. berghei-infected mice at a dose of 15 mg/kg/day ip. The assay revealed growth inhibition of 59.1 and 69.5% at days 5 and 7 postinfection, respectively, although some toxicity was observed. Zebrafish larvae were used as a model to determine the type of toxicity, and the results showed cardiac toxicity. The methanol extract was also studied, and it displayed moderate antiplasmodial properties in vitro. This extract contained the known flavonoids, quercetin, 3'-O-hydroxysulfonylquercetin, quercitrin, and isoquercitrin as well as ellagic acid, which showed high to low activity against the 3D7 P. falciparum strain.

Preisocalamendiol, Shyobunol and Related Oxygenated Sesquiterpenes from Bolivian Schinus molle Essential Oil.

Five batches of Bolivian Schinus molle essential oils were obtained from pilot and industrial-scale hydrodiffusions. They were analyzed by gas chromatography to find 80 known compounds and two unknown molecules. In particular, preisocalamendiol (5.6-11.0 %) was found to be an important constituent of these oils, along with shyobunol (0.6-3.2 %) and several other related oxygenated sesquiterpenes. These compounds, usually found in Acorus calamus, had not been reported altogether in S. molle essential oils previously. These findings, in light of the GABAA positive modulating effect of shyobunone and preisocalamendiol, along with some traditional uses of S. molle, suggest that further investigation of the tranquilizing properties of these Bolivian oils would be of interest.

Dirchromones: Cytotoxic Organic Sulfur Compounds Isolated from Dirca palustris.

Eight novel organic sulfur compounds featuring an unprecedented structure among natural organosulfur molecules are reported. The identified compounds, named dirchromones (1-8), were isolated from a dichloromethane extract of the roots, bark, and wood of Dirca palustris, an endemic shrub of eastern North America. Their identification was based on thorough NMR, IR, and HRMS spectroscopic data interpretation. These compounds showed cytotoxic and mild Gram-positive antibacterial activities in vitro, while being inactive against Gram-negative Escherichia coli and the yeast Candida albicans. This is the first report of sulfur-containing compounds from a species of the Thymelaeaceae.