Cassane Diterpenes Research Articles

Discovery of diversified cassane diterpenoids as potent antibacterial agents from Caesaplinia pulcherrima and their mechanisms.

Natural products play a significant role in the development of novel bactericide candidates. Caesalpinia pulcherrima, a traditional medicine, had anti-inflammatory, antimicrobial, and antifeedant activities, therefore the previous bioassay results of C. pulcherrima implied that its main active ingredients may have potential to be used as botanical bactericides. Bio-guided isolation of C. pulcherrima was conducted to obtain 11 novel cassane diterpenoids (capulchemins A-K) and 10 known sesquiterpenes. Their structures were established by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. Capulchemins A-F possess a rare aromatic C ring, while capulchemin K with a 15,16-degradative carbon skeleton represents a rare group of cassane diterpenes. Capulchemin A exhibited remarkable antibacterial activity against four phytopathogenic bacteria, particularly against Pseudomonas syringae pv. actinidae and Bacillus cereus, with minimal inhibitory concentration values of 3.13 μM. Meanwhile, capulchemin A showed significant control effect on kiwifruit canker in vivo. Further investigation of its mechanism of antibacterial activity revealed that compound 1 was closely related to destroy cell membrane to cause cell death. Additionally, some of those cassane diterpenoids showed potential antifeedant against Mythimna separate walker and Plutella xylostella. Consequently, capulchemin A could have the potential to be used as a template for the development for new eco-friendly NP-based bactericides. These data contribute to a better understanding of the antibacterial activity of cassane diterpenes. Cassane diterpenes have been discovered to be leading to broad application prospects in the development as novel botanical bactericides. © 2023 Society of Chemical Industry.

Distinctive Cassane Diterpenoids Corroborated Biogenetic Evolutionary Process from Caesalpinia mimosoides with Anti‐renal Fibrosis Activity

Comprehensive SummaryEighteen diterpenoids were isolated from the seeds of Caesalpinia mimosoides, including four extremely infrequent cassane diterpenes, together with nine new and five known structures. Compounds 7 and 8 represent the first examples of cassane diterpenoids fused with a ketone carbonyl and a ternary oxygen ring at C‐4, respectively. Compounds 9 and 10 possess a rare five‐member ring in cassane diterpenes. Intriguingly, these isolated components are a clue to the fact that there are lower and higher levels in the plant secondary metabolites, demonstrating the evolution of secondary metabolism of C. mimosoides. All the isolated compounds were tested for their anti‐renal fibrosis activity against TGF‐β1 induced NRK‐52E cell model. The mRNA levels of fibrosis marker α‐SMA, E‐cadherin, Collagen I were tested by qRT‐PCR. The data showed compounds 6 and 9 exhibited the best anti‐renal fibrosis activity and provided preliminary structure−activity relationships.

New Cassane Diterpenoids from the Seed Kernels of Caesalpinia cucullata, Exhibit Anti‐inflammatory Effect in vitro by Inhibiting iNOS Enzymatic Activity

Main observation and conclusionInflammation is a complex biological response to stimulation. Natural cassane diterpenoids from Caesalpinia genus exhibit significant anti‐inflammation activity. Eight new cassane diterpenoids (1—8) along with seven known ones (9—15) were obtained from the seed kernels of Caesalpinia cucullata Roxb. This is the first report on chemical investigation of the seed kernels of C. cucullata, and the cassane diterpenes were found in this plant for the first time. Their structures were elucidated based on the extensive spectroscopic analyses, and the absolute configurations were identified by ECD calculation and X‐ray crystallography. All compounds were evaluated for their anti‐inflammation activity by inhibiting NO production in LPS‐induced RAW 264.7 cells. Compounds 1—2 and 9—11 exhibited effective inhibitory activity with inhibition rate more than 50%. The iNOS enzyme activity and molecular docking experiments were performed to explore the preliminary mechanism. Eventually, a potential anti‐inflammatory mechanism revealed that the bioactive cassane inhibited overproduction of NO by targeting key residues in the iNOS active cavity to reduce iNOS enzymatic activation.

Four new cassane-type diterpenoids from the seed kernels of Caesalpinia cucullata Roxb.

The first investigation of chemical composition in seed kernels of Caesalpinia cucullata Roxb. resulted in the separation of four new cassane diterpenes, including three furanoditerpenes (1, 2 and 4) and one tricyclic type (3). It was the first found cassane diterpenoids from this plant. Their gross structures were elucidated by means of comprehensive spectroscopic analysis (UV, IR, NMR, HRESIMS) as well as electronic circular dichroism (ECD) calculation. The compound 1 possess a rare isomerized dihydrofuran ring in structure framework. In bioassay, compounds 1-4 exhibited moderate anti-inflammatory activity by inhibiting production of NO in LPS-induced RAW 264.7 cells.

Five new cassane diterpenes from the seeds and bark of Erythrophleum suaveolens

Five new cassane-type diterpenoid heterosides, i. e. two cassane-type amides (1–2), two erythrophlamine-type amine esters (3–4) and a non‑nitrogenous erythrophlamine analogue (5) were isolated from the root barks (1–2) and the seeds (3–5) of Erythrophleum suaveolens. Their structures were unambiguously established by interpretation of their HRESIMS, 1D and 2D NMR data, and chemical degradation for sugar determination. Compounds 3–5 were evaluated for their cytotoxicity against a panel of three cell lines, revealing modest to strong activities.

Therapeutic effects of Caesalpinia minax Hance on complete Freund's adjuvant (CFA)-induced arthritis and the anti-inflammatory activity of cassane diterpenes as main active components

Ethnopharmacological relevanceSeeds of Caesalpinia minax Hance called ‘Ku-Shi-Lian’ (KSL) in China have been used as Zhuang or Dai folk medicines for treatment of common cold, fever, rheumatoid arthritis and dysentery for hundred years. Aim of the studyThis study aimed to investigate therapeutic efficacy of KSL extract using complete Freund's adjuvant (CFA) induced arthritis in a rat model and the anti-inflammatory activity of cassane diterpenes as the main active material basis of this herb. Materials and methodsArthritis was induced in male Wistar rats (200–220 g) by immunization with CFA. Dexamethasone (DXMS) and Tripterygium glycosides (TG) were chosen as the positive drugs. Water soluble fraction (CMW, 1000 and 2000 mg/kg) and chloroform soluble fraction (CMC, 400 and 800 mg/kg) of KSL were orally administered from day 1 and continued for 21 days. Change of paw swelling perimeter, arthritics score, body weight growth, were observed, and the production of TNF-α, IL-1β and IL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The histological changes in the ankle joint were analyzed in adjuvant induced arthritis rats. Moreover, the inhibitory effect on mRNA expression of proinflammatory cytokine IL-1β, IL-6 and TNF-α of fourteen cassane diterpenes obtained from CMC extract were valued using the RAW 264.7 macrophages cell stimulated by lipopolysaccharide (LPS) assay. ResultsThe chloroform soluble fraction (CMC) showed the significantly suppressed change of paw swelling perimeter, arthritics score and increased body weight loss. The overproduction of TNF-α, IL-1β and IL-6 were remarkably suppressed in the serum. Fourteen cassane derivatives as the main constituents of CMC extract showed the promising activity on the expression mRNA of cytokine IL-1β, IL-6 and TNF-α produced by macrophages cells. ConclusionsIn this study, the chloroform soluble fraction of ‘KSL’ (seeds of C. minax) was found to exert an anti-RA activity significantly in vivo for the first time, which indicted this fraction might be used as a powerful therapeutic agent for arthritis treatments. Cassane diterpenes, as the main constituents in this fraction, showed the anti-inflammation activity through the regulation of cytokine expression, which might be developed as target-agents for this national herb further developing.

Three new cassane diterpenes from the seeds of Caesalpinia minax Hance

Four fractions were prepared from the crude extract of Caesalpinia minax Hance and the inhibitory activity of nitric oxide (NO) production release of RAW 264.7 cells stimulated by lipopolysaccharide (LPS) was evaluated. The ethyl acetate (EtOAc) fraction showed obvious inhibitory effect. Bioassay-guided fractionation led to the isolation of three new cassane diterpenes, caesalmin X (1), caesalmin Y (2) and caesalmin Z (3), together with 19 known cassane diterpenoids (4–22). Their structures were mainly characterised on the basis of extensive spectroscopic analyses and comparison with reported data. Moreover, three compounds (20–22) which possessed furanditerpenoid 7,17-lactone structures, displayed moderate activities, with IC50 value of 29.85, 27.38 and 25.40 μM, respectively.

New cassane diterpenes from the fruits of Caesalpinia mimosoides Lam.

Six new cassane diterpenes, caesmimosins A-F (1–6) were isolated from the fruits of Caesalpinia mimosoides Lam. Their structures were identified by 1D and 2D NMR spectral data. Compounds 1–6 were evaluated for their cytotoxicity on HL-60, SMMC-7721, A-549, MCF-7 and SW-480 human cancer cell lines, they did not show inhibitory cytotoxic activities at a concentration of 40μM against the five cell lines.

Short Route to Cassane-Type Diterpenoids: Synthesis of the Supposed Structure of Benthaminin 1.

A short route toward aromatic cassane diterpenes from labdane terpenoids has been developed. In the key step, the aromatic ring with the oxygenated function at C-12 and the characteristic carbon group at C-14 of the target compounds is elaborated via a Diels-Alder/aromatization sequence of a furanosesquiterpene and methyl propiolate. On this basis, the synthesis of the proposed structure of benthaminin 1 from trans-communic acid has been achieved. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.

Caesalmins N-Q, new cassane diterpenes from the seeds of Caesalpinia minax

Four new cassane diterpenes, named caesalmins N-Q together with six known compounds (1⿿10) were isolated from the MeOH extract of seeds of Caesalpinia minax Hance. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and HRESIMS data. All the new compounds were evaluated for their antiproliferative activities in vitro against three human cancer cell lines, and they showed weak cytotoxic activity with the IC50 values ranging from 45.4 to 78.1μM.

Cassane diterpenes with oxygen bridge from the seeds of Caesalpinia sappan

The seeds of the medicinal plant Caesalpinia sappan yielded fourteen cassane-type diterpenes, including six new rearranged ones named as caesalppans A-F (1–6). Their structures were elucidated by spectroscopic analysis and comparison with literature data. The isolated new compounds 1–6 possess lactone-type cassane diterpenoid skeleton with an oxygen bridge between C-19 and C-20, and were tested cytotoxic activity against four cancer cell lines using the MTT method.

Novel cassane diterpenes from the seeds of Caesalpinia decapetala and their antiproliferative activity

Two new cassane diterpenes, caesaldecapes A-B (1–2), were isolated from the seeds of Caesalpinia decapetala. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and HRESIMS. Compounds 1–2 are novel examples of rearranged cassane diterpenes obtained from C. decapetala. The two compounds were evaluated for their antiproliferative activity in vitro against four human cancer cell lines, and compound 1 showed selectively cytotoxic activity against KB cancer cell lines, with an IC50 value at 9.6μM.

Cassane diterpenes from the seed kernels of Caesalpinia sappan

Eight structurally diverse cassane diterpenes named tomocins A–H were isolated from the seed kernels of Vietnamese Caesalpinia sappan Linn. Their structures were determined by extensive NMR and CD spectroscopic analysis. Among the isolated compounds, tomocin A, phanginin A, F, and H exhibited mild preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived condition without causing toxicity in normal nutrient-rich conditions.

Six new cassane diterpenes from the twigs and leaves of Tara (Caesalpinia spinosa Kuntze)

Six new cassane diterpenes, isoneocaesalpin H (1), caespinosin A (2), caespinosin B (3), a cassane diterpene with unique 6/6/7 carbon rings, and caespinosins C–E (4–6) were isolated from the twigs and leaves of Tara (Caesalpinia spinosa Kuntze). The absolute configuration of isoneocaesalpin H (1) was determined by single-crystal X-ray crystallographic analysis. Compound 3 represents a class of rare natural cassane diterpene bearing unique 6/6/7 carbon rings. Their structures were identified by 1D and 2D NMR spectral data. Cassane diterpenes were firstly reported from Tara. Compounds 1–5 were evaluated for their cytotoxicity on HL-60, SMMC-7721, A-549, MCF-7 and SW-480 human cancer cell lines, but they were inactive.

Three new cassane diterpenes from the seeds of Caesalpinia sappan

Three new cassane furanoditerpenes, phanginins N–P (1–3), together with four known ones were isolated from the seeds of Caesalpinia sappan. Their structures were elucidated on the basis of spectroscopic analysis including HRESIMS, 1D and 2D NMR techniques. Evaluation of all the compounds for cytotoxicity against three human cancer cell lines (HepG-2, MCF-7 and HCT-8) showed insignificant results (IC50>10μM).

Further Diterpenes from the Seeds of Caesalpinia minaxHance

AbstractThree new cassane‐type diterpenes, neocaesalpin AF (1), neocaesalpin AG (2), and neocaesalpin AH (3), were isolated from the seeds of Caesalpinia minax Hance. Their structures were elucidated on the basis of extensive spectroscopic analyses. The partially hydrogenated lactone unit in a tetracyclic cassane diterpene in 2 is rarely encountered in the cassane diterpenes isolated from the genus Caesalpinia. All compounds were evaluated for their in vitro cytotoxic activities against HCT‐8 and MCF‐7 human cancer cell lines.

Cassane diterpenes from Caesalpinia platyloba

The dichloromethane extract from the leaves of Caesalpinia platyloba provided cassane diterpenes whose structures were determined as (-)-(5S,6R,8S,9S,10R,14R)-6-acetoxyvouacapane (1), (-)-(5S,6R,8S,9S,10R,12Z,14R)-6-acetoxycassa-12,15-diene (3), and (-)-(5S,6R,8S,9S,10R,13E)-6-acetoxycassa-13,15-diene (4). Compound 1 was chemically correlated with (-)-(5S,6R,8S,9S,10R,14R)-6-hydroxyvouacapane (2), (+)-(5S,8S,9S,10R,14R)-6-oxovouacapane (5), and (+)-(5S,6S,8S,9S,10R,14R)-6-acetoxyvouacapane (6), the last one previously isolated from Dipteryx lacunifera. The absolute configurations of all six diterpenes 1-6 were established by comparison of DFT calculated vibrational circular dicroism spectra of 1, 2 and 5 with those obtained experimentally. In addition, several reported chemical shifts for 2 and 5 were reassigned based on two-dimensional NMR measurements.

ChemInform Abstract: Voulkensin C—E, New 11‐Oxocassane‐Type Diterpenoids and a Steroid Glycoside from Caesalpinia volkensii Stem Bark and Their Antiplasmodial Activities.

AbstractThree new cassane diterpenes, voulkensin C (Ia), D (Ib), and E (II), and a new steroidal‐stigmasterol glycoside (III) are isolated together with seven known compounds.

Four new cassane diterpenes from the seeds of Caesalpinia minax

In our survey on the chemical composition of traditional Chinese medicines to further elucidate their chemical substances for the treatment of diseases, we investigated the chemical constituents of the seeds of plants Caesalpinia minax. The investigation led to the isolation and identification of four new cassane diterpenes, caesalpines A–D (1–4). Their structures were elucidated on the basis of extensive 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) and mass (ESIMS and HR-ESIMS) spectroscopic data analyses. The phytochemical results imply that cassane diterpenes are maybe regarded as the characteristic constituents of C. minax.

Novel cassane diterpenes from the seeds of Caesalpinia minax

Three new cassane diterpenes, sucutiniranes G (1), H (2) and I (3) were isolated from the seeds of Caesalpinia minax Hance. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, CD, 1D and 2D NMR). All compounds were evaluated for cytotoxic activities against MCF-7 and HepG-2 human cancer cell lines.