Recent advances in the chemistry and biology of oleanolic acid and its derivatives.

The pentacyclic triterpenes represent a significant class of plant bioactives with a variety of structures and a wide array of biological activities. These are biosynthetically produced via the mevalonate pathway although occasionally mixed pathways may also occur to introduce structural divergence. Oleanolic acid is one of the most explored bioactive from this class of compounds and possesses a broad spectrum of pharmacological and biological activities including liver protection, anti-cancer, atherosclerosis, anti-inflammation, antibacterial, anti-HIV, anti-oxidative, anti-diabetic etc. This review provides an overview of the latest research findings, highlighting the versatile medicinal and biological potential of oleanolic and its future prospects.

Exploring the osteogenic potential of semisynthetic triterpenes from Combretum leprosum: An in vitro and in silico study.

Combretum leprosum Mart. is a plant of the Combretaceae family, widely distributed in the Northeast region of Brazil, popularly used as an anti-inflammatory agent, and rich in triterpenes. This study evaluated in vitro and in silico potential osteogenic of two semisynthetic triterpenes (CL-P2 and CL-P2A) obtained from the pentacyclic triterpene 3ß,6ß,16ß-trihydroxylup-20(29)-ene (CL-1) isolated from C. leprosum. Assays were carried out in cultured murine osteoblasts (OFCOL II), first investigating the possible toxicity of the compounds on these cells through viability assays (MTT). Cell proliferation and activation were investigated by immunohistochemical evaluation of Ki-67, bone alkaline phosphatase (ALP) activity, and mineralization test by Von Kossa. Molecular docking analysis was performed to predict the binding affinity of CL-P2 and CL-P2A to target proteins involved in the regulation of osteogenesis, including: bone morphogenetic protein 2 (BMP-2), proteins related to Wingless-related integration (WNT) pathway (Low-density lipoprotein receptor-related protein 6-LRP6 and sclerostin-SOST), and receptor activator of nuclear factor (NF)-kB-ligand (RANK-L). Next, Western Blot and immunofluorescence investigated BMP-2, WNT, RANK-L, and OPG protein expressions in cultured murine osteoblasts (OFCOL II). None of the CL-P2 and CL-P2A concentrations were toxic to osteoblasts. Increased cell proliferation, ALP activity, and bone mineralization were observed. Molecular docking assays demonstrated interactions with BMP-2, LRP6, SOST, and RANK-L/OPG. There was observed increased expression of BMP-2, WNT, and RANK-L/OPG proteins. These results suggest, for the first time, the osteogenic potential of CL-P2 and CL-P2A.

Synthesis and anticancer evaluation of new lupane triterpenoid derivatives containing various substituent at the 2 or 3 position.

Betulonic acid benzyl ester 1 has been subjected to a series of structural modifications for the purpose of new triterpenoid synthesis and evaluating for anticancer activity. The one-pot two step synthesis of 2α-(aminomethyl)betulinic acid benzyl ester derivatives 3a-f (yield 46-69 %) was achieved by the Mannich reaction of compound 1 with methyleneiminium salts, generated in situ from N,N-disubstituted bis(amino)methanes 2a-f by the action of acetyl chloride in dichloromethane, and subsequent reduction of aminomethylation products with sodium borohydride. Minor 2ß-(aminomethyl) triterpenoids 4c,d,f were also isolated (yield 6-15 %). We found, that the stereoselective reaction of triterpenoid 1 with acetylides, generated at -78 °C from alkynes in the presence of n-BuLi, has been useful and noteworthy as the key step in providing of new alkyne substituted triterpenoids - benzyl 3-alkynyl-3-deoxy-2(3),20(29)-lupadiene-28-oates or 3-deoxy-2(3)-dehydro-28-oxoallobetulin derivative. The new compounds were examined for anticancer activity against the human cell lines (MTT assay). All tested derivatives were non-toxic on human fibroblasts. The 3-(phenylethynyl)lupa-2(3),20(29)-diene 9 showed selective cytotoxicity on cervical cancer cell lines. Tumor cells death trigged by the most active compound 4f resulted from apoptotic processes. These data make the series of synthesized 2 or 3 substituted lupane derivatives as promising compounds with anticancer potential.

Unraveling the Impact of Six Pentacyclic Triterpenes Regulating Metabolic Pathways on Lung Carcinoma Cells.

Recently, there has been great interest in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, and lupane-type triterpenes are phytochemicals that exert significant activity against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose-limiting toxic effects and chemoresistance. Herein, we investigated six pentacyclic triterpenes, oleanolic acid, ursolic acid, asiatic acid, betulinic acid, betulin, and lupeol, on NSCLC A549 cells. These triterpenes have several structural variations that can influence the activation/inactivation of key cellular pathways. From our results, we determined that most of these triterpenes induced apoptosis, S-phase and G2/M-phase cycle arrest, the downregulation of ribonucleotide reductase (RR), reactive oxygen species, and caspase 3 activation. For chemoresistance markers, we found that most triterpenes downregulated the expression of MAPK/PI3K, STAT3, and PDL1. In contrast, UrA and AsA also induced DNA damage and autophagy. Then, we theoretically determined other possible molecular targets of these triterpenes using the online database ChEMBL. The results showed that even slight structural changes in these triterpenes can influence the cellular response. This study opens up promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

Metabolic discrimination of Thymus, Zataria, and Ziziphora genera by NMR-based metabolomics.

Thyme is a commercial spice widely used in food, cosmetics, and pharmaceutical industries. Three popular genera in food and traditional medicine, including Zataria Boiss., Thymus L., and Ziziphora L., are considered as thyme-like plants in Iran. Thyme has been standardised based on phenolic monoterpenes, which are abundant in the essential oils of these three genera. Apart from monoterpenes, the flavonoid naringenin, the triterpene oleanolic acid, and phytosterols such as ß-sitosterol were abundant in Zataria, Thymus, and Ziziphora samples, respectively. Therefore, employing current analytical techniques on the basis of thymol and carvacrol may be insufficient to differentiate Thymus spp from similar medicinal plants including Zataria and Ziziphora spp. In this study, we applied NMR-based metabolomics using multivariate analyses to develop quality control of thyme and their similar products. Our findings revealed that NMR-based metabolomics can be a useful approach in differentiating Zataria, Thymus, and Ziziphora.

Development of a high-speed and ultrasensitive UV/Vis-CM for detecting total triterpenes in traditional Chinese medicine and its application.

This study proposes a novel colorimetric method based on the ultraviolet/visible spectrophotometry-colorimetric method (UV/Vis-CM) for detecting and quantifying total triterpenoids in traditional Chinese medicine. By incorporating the colourants 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid, triterpenoid compounds colour development became more sensitive, and the detection accuracy was significantly improved. 2-hydroxy-5-methylbenzaldehyde and concentrated sulfuric acid were incorporated in a 1:3 vol ratio at room temperature to react with the total triterpenes for 25 min, incorporated to an ice bath for 5 min, and then detected at the optimal absorption wavelength. The accuracy and reliability of this method were verified by comparison with high-performance liquid chromatography and four other colorimetric methods. Additionally, this approach has the advantages of not requiring heating during operation, high sensitivity, short usage time, low solvent usage, and low equipment costs. This study not only offers a reliable method for detecting total triterpenes in traditional Chinese medicine but also offers a rapid detection tool for on-site testing and large-scale screening, laying a foundation for the modernization of traditional Chinese medicine research, quality control, and drug development.

Notoginseng leaf triterpenes promotes angiogenesis by activating the Nrf2 pathway and AMPK/SIRT1-mediated PGC-1/ERα axis in ischemic stroke.

Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.

Triterpenes from antler-shaped fruiting body of Ganoderma lucidum and their hepatoprotective activities.

Seven previously undescribed triterpenes (1-7), as well as one triterpene (8) previously described as a synthetic product, were isolated from the antler-shaped fruiting body of Ganoderma lucidum. Their structures were established based on comprehensive spectroscopy analysis. At a concentration of 10 µM, (24E)-3-oxo-15α-acetoxy-lanosta-7,9(11),24-trien-26-al (3) and (24R,25S)-3-oxo-lanosta-7,9(11)-dien-25-ethoxyl-24,26-diol (5) provided significant protection against acetaminophen-induced necrosis in human HepG2 liver cancer cells, and the cell survival rates were 69.7 and 76.1% respectively, similar to that of the positive control (glutathione, 72.1%). Based on the present results, these compounds could be potential hepatoprotective agents.

Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

Mexican Coccoloba uvifera L. Leaf and Fruit Extracts: Identification of Pentacyclic Triterpenes and Volatile Profile by GC-MS.

Mexican Coccoloba uvifera fruit contains polyphenols, flavonoids, and anthocyanins, while in the leaves, lupeol, α- and ß-amyrin have been previously identified by HPLC. However, the low resolution by HPLC of pentacyclic triterpenes (PTs) is a limitation. Moreover, the volatile profile of C. uvifera fruit is still unknown. Therefore, this study aimed to identify PTs in C. uvifera leaf and fruit extracts by CG-MS analysis and to determine the volatile profile of C. uvifera pulp by headspace solid-phase microextraction. The results showed trimethylsilylated compounds of standards lupeol, α- and ß-amyrin, indicating that the silylation reaction was suitable. These trimethylsilylated compounds were identified in leaf and fruit extracts. The fruit volatile profile revealed the presence of 278 esters, 20 terpenes, 9 aldehydes, 5 alcohols, and 4 ketones. The fruit showed a high content of esters and terpenes. Due to their flavour properties, esters are essential for the food, cosmetics, and pharmaceutics industries. Moreover, terpenes in the fruit, such as menthone, ß-elemene, junipene, and ß-caryophyllene have the potential as anticancer and phytopathogen agents. The results indicated that GC-MS is an alternative to HPLC approaches for identifying PTs. Besides, identifying volatile compounds in the fruit will increase the value of this plant and expand its application. Identifying PTs and volatile compounds in Mexican C. uvifera leads to a better understanding of the potential benefits of this plant. This would increase the consumption of Mexican C. uvifera fresh or as functional ingredients in nutraceutical or pharmaceutical products.

A Review on Ethnobotany, Phytochemistry and Pharmacological Activities of Euphorbia antiquorum L.

Euphorbia antiquorum L. is a small plant in the Euphorbiaceae family that is found primarily in tropical and subtropical Asia. It has a long tradition of being utilized in Chinese, Ayurvedic, and other traditional systems for a variety of ailments. To date, More than 116 bioactive constituents were isolated from Euphorbia antiquorum, with diterpenoids being the most abundant. Extracts and isolated chemicals from various portions of the plant have demonstrated significant pharmacological activities such as anti-inflammatory, analgesic, antidiabetic, anticancer etc. It is necessary to conduct an in-depth investigation of the phytochemicals along with the pharmacological properties of E. antiquorum. This review summarised the knowledge of ethnobotany, phytochemistry and pharmacological activities of the plant which will provide a better understanding to clarify the traditional uses of the species and its relation to modern pharmacology which will ultimately pave the way for its clinical application.

Mode of administration influences plasma levels of active Centella asiatica compounds in 5xFAD mice while markers of neuroinflammation remain unaltered.

Introduction: A water extract of Centella asiatica (L.) Urban [Apiaceae] (CAW) has demonstrated cognitive-enhancing effects in mouse models of Alzheimer's disease and aging, the magnitude of which is influenced by whether CAW is delivered in the drinking water or the diet. These cognitive benefits are accompanied by improvements in oxidative stress and mitochondrial function in the brain, two pathways related to the neuroinflammatory response. The effect of CAW on neuroinflammation, however, has not been directly studied. Here, we investigated the effect of CAW on neuroinflammation in 5xFAD mice and compared plasma levels of CAW's active compounds following two modes of CAW administration. Methods: Eight-to-nine-month-old male and female 5xFAD mice and their wild-type littermates were administered CAW in their diet or drinking water (0 or 1,000 mg/kg/day) for five weeks. Immunohistochemistry was performed for ß-amyloid (Aß), glial fibrillary acidic protein (GFAP), and Griffonia simplicifolia lectin I (GSL I) in the cortex and hippocampus. Gene expression of inflammatory mediators (IL-6, TNFα, IL-1ß, TREM2, AIF1, CX3CR1, CX3CL1, CD36, C3AR1, RAGE, CCR6, CD3E) was measured in the deep grey matter. Results: CAW decreased cortical Aß plaque burden in female 5xFAD mice administered CAW in the drinking water but had no effect on Aß plaques in other treatment groups. CAW did not impact elevated levels of GFAP or GSL I in 5xFAD mice, regardless of sex, brain region, or mode of CAW administration. In the deep grey matter, CAW increased C3AR1 expression in 5xFAD females administered CAW in the drinking water and decreased IL-1ß expression in 5xFAD males administered CAW in the diet. CAW had no effect, however, on gene expression levels of any other inflammatory mediator in the deep grey, for either sex or mode of CAW administration. Mice administered CAW in the drinking water versus the diet had significantly higher plasma levels of CAW compounds. Discussion: CAW had little impact on the neuroinflammatory markers selected for evaluation in the present study, suggesting that the cognitive benefits of CAW may not be mediated by an anti-inflammatory effect or that additional molecular markers are needed to fully characterize the effect of CAW on neuroinflammation.

Comparison of the Antioxidant Potency of Four Triterpenes of Centella asiatica against Oxidative Stress.

We comparatively evaluated the antioxidant properties of key triterpenes from Centella asiatica, including asiatic acid (AA), asiaticoside, madecassic acid, and madecassoside, in several cell types, including skin fibroblasts, macrophages, hepatocytes, and endothelial cells, under conditions promoting oxidative stress. AA conferred the highest viability on Hs68 cells exposed to ultraviolet B (UVB) irradiation. Triterpene pretreatment attenuated the UVB-induced generation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the UVB-induced depletion of glutathione (GSH) in skin fibroblasts. AA most potently inhibited UVB-induced MMP generation, resulting in increased intracellular collagen levels. Pretreatment with triterpenes, particularly AA, significantly improved cell viability and attenuated TBHP-induced levels of ROS, alanine aminotransferase, and aspartate aminotransferase in HepG2 cells. Triterpenes attenuated ROS levels and reduced MDA and GSH expression in EA.hy926 cells. In RAW264.7 macrophages, production of nitric oxide, tumor necrosis factor-α, and interleukin-6 (indicators of LPS-induced oxidative damage) was significantly reduced by treatment with any of the triterpenes. Statistical analyses of triterpene biological activities using principal component analysis and hierarchical clustering revealed that AA exerted the greatest overall influence and showed remarkable activity in Hs68 and HepG2 cells.

Can Asiatic Acid from Centella asiatica Be a Potential Remedy in Cancer Therapy?-A Review.

Centella asiatica has been recognized for centuries in Eastern medicine for its pharmacological properties. Due to the increasing prevalence of oncological diseases worldwide, natural substances that could qualify as anticancer therapeutics are becoming increasingly important subjects of research. This review aims to find an innovative use for asiatic acid (AA) in the treatment or support of cancer therapy. It has been demonstrated that AA takes part in inhibiting phosphorylation, inducing cell death, and reducing tumor growth and metastasis by influencing important signaling pathways, such as PI3K, Akt, mTOR, p70S6K, and STAT3, in cancer cells. It is also worth mentioning the high importance of asiatic acid in reducing the expression of markers such as N-cadherin, ß-catenin, claudin-1, and vimentin. Some studies have indicated the potential of asiatic acid to induce autophagy in cancer cells through changes in the levels of specific proteins such as LC3 and p62. It can also act as an anti-tumor immunotherapeutic agent, thanks to its inductive effect on Smad7 in combination with naringenin (an Smad3 inhibitor). It seems that asiatic acid may be a potential anticancer drug or form of adjunctive therapy. Further studies should take into account safety and toxicity issues, as well as limitations related to the pharmacokinetics of AA and its low oral bioavailability.

Triterpenes G-A and G-E from Galphimia glauca with anti-inflammatory and anti-arthritic activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Galphimia glauca is a medicinal plant that treats inflammatory and anti-rheumatic problems. Its anti-inflammatory capacity has been reported pharmacologically, attributed to the triterpenes G-A and G-E. AIM: The objective of the present work was to measure the anti-inflammatory and immunomodulatory effect of the methanolic extract (GgMeOH) of Galphimia glauca and the isolated galphimines G-A and G-E, first in an acute test of plantar edema with carrageenan, and later in the model of experimental-induced arthritis with CFA. The effect was measured by quantifying joint inflammation, the concentration of pro- (TNF-α, IL-6, IL-17) and anti-inflammatory (IL-10, and IL-4) cytokines, and the ADA enzyme in joints, kidneys, and spleen from mice with experimental arthritis. METHOD: The extract and the active triterpenes were obtained according to established methods using different chromatographic techniques. Female ICR strain mice were subjected to intraplantar administration with carrageenan and treated with different doses of GgMeOH, G-A, and G-E; edema was monitored at different times. Subsequently, the concentration of TNF-a and IL-10 in the spleen and swollen paw was quantified. Meloxicam (MEL) was used as an anti-inflammatory control drug. The most effective doses of each treatment were analyzed using a complete Freunds adjuvant (CFA)-induced experimental arthritis model. Joint inflammation was followed throughout the experiment. Ultimately, the concentration of inflammation markers, oxidant stress, and ADA activity was quantified. In this experimental stage, methotrexate (MTX) was used as an antiarthritic drug. RESULTS: Treatments derived from G. glauca, GgMeOH (DE50 = 158 mg/kg), G-A (DE50 = 2 mg/kg), and G-E (DE50 = 1.5 mg/kg) caused an anti-inflammatory effect in the plantar edema test with carrageenan. In the CFA model, joint inflammation decreased with all natural treatments; GgMeOH and G-A inhibited the ADA enzyme in all organs analyzed (joints, serum, spleen, left and right kidneys), while G-E inhibited the enzyme in joints, serum, and left kidney. CFA caused an increase in the weight index of the organs, an effect that was counteracted by the administration of G. glauca treatments, which also modulate the response to the cytokines analyzed in the different organs (IL-4, IL-10, IL-17, IL-6, and TNF- α). CONCLUSION: It is shown, for the first time, that the GgMeOH extract and the triterpenes G-A and G-E of Galphimia glauca have an anti-arthritic effect (anti-inflammatory, immunomodulatory, antioxidant, and ADA inhibitor), using an experimental arthritis model with CFA. Therefore, knowledge of the plant as a possible therapeutic agent for this rheumatic condition is expanding.

The Nitrogen Content in the Fruiting Body and Mycelium of Pleurotus Ostreatus and Its Utilization as a Medium Component in Thraustochytrid Fermentation.

Following the idea of a circular bioeconomy, the use of side streams as substitutes for cultivation media (components) in bioprocesses would mean an enormous economic and ecological advantage. Costly compounds in conventional media for the production of the triterpene squalene in thraustochytrids are the main carbon source and complex nitrogen sources. Among other side streams examined, extracts from the spent mycelium of the basidiomycete Pleurotus ostreatus were best-suited to acting as alternative nitrogen sources in cultivation media for thraustochytrids. The total nitrogen (3.76 ± 0.01 and 4.24 ± 0.04%, respectively) and protein (16.47 ± 0.06 and 18.57 ± 0.18%, respectively) contents of the fruiting body and mycelium were determined. The fungal cells were hydrolyzed and extracted to generate accessible nitrogen sources. Under preferred conditions, the extracts from the fruiting body and mycelium contained 73.63 ± 1.19 and 89.93 ± 7.54 mM of free amino groups, respectively. Cultivations of Schizochytrium sp. S31 on a medium using a mycelium extract as a complex nitrogen source showed decelerated growth but a similar squalene yield (123.79 ± 14.11 mg/L after 216 h) compared to a conventional medium (111.29 ± 19.96 mg/L, although improvable by additional complex nitrogen source).

Plant In Vitro Culture Factories for Pentacyclic Triterpenoid Production.

Pentacyclic triterpenoids are a diverse subclass of naturally occurring terpenes with various biological activities and applications. These compounds are broadly distributed in natural plant resources, but their low abundance and the slow growth cycle of plants pose challenges to their extraction and production. The biosynthesis of pentacyclic triterpenoids occurs through two main pathways, the mevalonic acid (MVA) pathway and the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, which involve several enzymes and modifications. Plant in vitro cultures, including elicited and hairy root cultures, have emerged as an effective and sustainable system for pentacyclic triterpenoid production, circumventing the limitations associated with natural plant resources. Bioreactor systems and controlling key parameters, such as media composition, temperature, light quality, and elicitor treatments, have been optimized to enhance the production and characterization of specific pentacyclic triterpenoids. These systems offer a promising bioprocessing tool for producing pentacyclic triterpenoids characterized by a low carbon footprint and a sustainable source of these compounds for various industrial applications.

An asiatic acid derived trisulfamate acts as a nanomolar inhibitor of human carbonic anhydrase VA.

This investigation delves into the inhibitory capabilities of a specific set of triterpenoic acids on diverse isoforms of human carbonic anhydrase (hCA). Oleanolic acid (1), maslinic acid (2), betulinic acid (3), platanic acid (4), and asiatic acid (5) were chosen as representative triterpenoids for evaluation. The synthesis involved acetylation of parent triterpenoic acids 1-5, followed by sequential reactions with oxalyl chloride and benzylamine, de-acetylation of the amides, and subsequent treatment with sodium hydride and sulfamoyl chloride, leading to the formation of final compounds 21-25. Inhibition assays against hCAs I, II, VA, and IX demonstrated noteworthy outcomes. A derivative of betulinic acid, compound 23, exhibited a Ki value of 88.1 nM for hCA VA, and a derivative of asiatic acid, compound 25, displayed an even lower Ki value of 36.2 nM for the same isoform. Notably, the latter compound displayed enhanced inhibitory activity against hCA VA when compared to the benchmark compound acetazolamide (AAZ), which had a Ki value of 63.0 nM. Thus, this compound surpasses the inhibitory potency and isoform selectivity of the standard compound acetazolamide (AAZ). In conclusion, the research offers insights into the inhibitory potential of selected triterpenoic acids across diverse hCA isoforms, emphasizing the pivotal role of structural attributes in determining isoform-specific inhibitory activity. The identification of compound 25 as a robust and selective hCA VA inhibitor prompts further exploration of its therapeutic applications.

Pentacyclic triterpenes from the leaves of Camellia hakodae Ninh.

Nine pentacyclic triterpene derivatives including new 3-O-cis-p-coumaroyl trichadenic acid B (1) and two new ursane-type triterpene derivatives, 11α,12-[1-(methyl)-2-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (2) and 11α,12-[2-(methyl)-1-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (3) were isolated from the leaves of Camellia hakodae Ninh., along with six known compounds (4-9). This is the first report on pentacyclic triterpenoids from this species. New compounds 1-3 and compound 7 were tested for cytotoxic activity against four human cancer cell lines (KB; Hep-G2; Lu; MCF-7) using the MTT assay to show moderate activity.

Larvicidal Activity against Spodoptera frugiperda of some Constituents from two Diospyros Species. In silico Pesticide-likeness Properties, Acetylcholinesterase Activity and Molecular Docking.

This report informs for the first time the chemical constituents of Diospyros xolocotzii and Diospyros digyna, the pesticidal and the acetylcholinesterase (AChE) inhibition potential of some compounds calculated by in silico approaches, the larvicidal activity against Spodoptera frugiperda of available compounds, the AChE inhibition of selected compounds, and the results of the molecular docking of the most active ones with this receptor. From the aerial parts of D. xolocotzii were isolated pentacyclic triterpenes (1-4, 6, 10, 11-13), phytosterols (15-17), and isodiospyrin (18), whereas the analysis of aerial parts of D. digyna conducted to the isolation of pentacyclic triterpenes (4, 5, 7-9, 11-14), (4S)-shinanolone (19), and scopoletin (20). For comparison purposes, origanal (21) was chemically prepared from 11. The in silico analysis showed that the tested compounds have pesticide potential. The larvicidal activities of 11>13>12 indicated that the increase of the oxidation degree at C-28 increases their bioactivity. Compounds 11 and 21 presented the higher inhibition in the acetylcholinesterase assay, and the higher binding energies, and for the interactionswith AChE by molecular docking. Both Diospyros species are sources of triterpenes with pesticidal potential and the molecular changes in lupane triterpenes correlate with the observed bioactivity and molecular docking.