Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Haplophyllum tuberculatum (Forssk.) A. Juss Essential Oils: Seasonal Contents Variation, Bioactivity of the Traditionally-favored, High-yield and Frequent-use Summer Season Oil.

Haplophyllum tuberculatum (Forssk.) A.Juss. volatile oils were obtained by distillation of the aerial parts of the plant growing in Libya during the summer and spring seasons. A yield and componential analysis revealed that the summer season oil, which is frequently used in traditional medicaments by North African communities, was high in yield (0.858%) compared to the spring season oil (0.47%), and distinguished by the presence of major and various diverse constituents, some of which are considered chemical markers. Owing to the traditional and high incidence of use of the summer-produced essential oil for the treatment of several disorders, including hepatic diseases, and fatigue, the oil was pharmacologically investigated for its varied bioactivities of anti-microbial, in vivo anti-oxidant, and in vitro anti-cancer properties. Thirty-three compounds were identified and represented 96.2% of the peaks in the GCchromatogram of the summer oil, in which the major volatile constituents were δ-3-carene (21.5%), bornyl acetate (16.9%), and limonene aldehyde (15.2%). The summer-based essential oil of the plant demonstrated moderate anti-bacterial activity against Gram-positive bacteria and a relatively strong antibacterial effect against Gram-negative bacteria as compared to the positive antibacterial controls, ampicillin and gentamicin, respectively. Also, antifungal activity against Aspergillus sp. was observed. The summerproduced oil also exhibited in vivo antioxidant and in vitro anti-cancer activities.

Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Six new coumarins from the roots of Toddalia asiatica and their anti-inflammatory activities.

We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC50) values of 3.22, 4.78, 8.90, and 4.31 µmol·L-1, respectively.

A Review of the Ethnomedicinal, Phytochemical, and Anticancer Properties of Melicope Species.

The genus Melicope, which consists of 230 species, stands out as the largest genus within the Rutaceae family. Melicope species are characterized by their evergreen nature and can range from shrubs to predominantly dioecious trees. The Melicope species have been utilized in traditional medicine to address a wide range of ailments, including fever, colds, cramps, and inflammation. These plants have gained significant attention due to their noteworthy ethnopharmacological and ethnomedicinal significance. Researchers have isolated numerous biologically active secondary metabolites from different Melicope species, which include polymethoxylated flavonoids, furanocoumarins, acetophenones, benzenoids, and quinolone alkaloids. These compounds exhibit diverse biological activities, such as antibacterial, antidiabetic, antifungal, and antiproliferative properties against human cancer cell lines. This review provides an update on the chemical constituents of the selected species of Melicope. The study also highlights the anticancer and cytotoxicity properties of the plant extracts and phytochemical constituents from Melicope species. Furthermore, the molecular mechanisms underlying the anticancer effects are elucidated. Overall, this review contributes to understanding the significant pharmacological potential of Melicope species and unlocking their chemical composition, emphasizing their relevance in the development of therapeutic agents, particularly in the field of cancer research.

Antibacterial and antibiotic potentiating capabilities of extracts isolated from Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus against human pathogenic bacteria.

Antibiotics which once a boon in medicine and saved millions of lives are now facing an ever-growing menace of antibacterial resistance, which desperately needs new antibacterial drugs which are innovative in chemistry and mode of action. For many years, the world has turned to natural plants with antibacterial properties to combat antibiotic resistance. On that basis, we aimed to identify plants with antibacterial and antibiotic potentiating properties. Seventeen different extracts of 3 plants namely Burkillanthus malaccensis, Diospyros hasseltii and Cleisthanthus bracteosus were tested against multi-drug resistant Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillinresistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). Antibacterial activity of hexane, methanol and chloroform extracts of bark, seed, fruit, flesh and leaves from these plants were tested using, disk diffusion assay, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Antibiotic potentiating capabilities were tested using time-kill assay. B. malaccensis fruit chloroform extract showed the biggest zone of inhibition against MRSA (13.00±0.0 mm) but C. bracteosus bark methanol extract showed the biggest inhibition zone against MSSA (15.33±0.6 mm). Interestingly, bark methanol extract of C. bracteosus was active against MRSA (8.7±0.6 mm), MSSA (7.7±0.6 mm) (Gram-positive) and A. baumannii (7.7±0.6 mm) (Gram-negative). Overall, the leaf methanol and bark methanol extract of C. bracteosus warrants further investigation such as compound isolation and mechanism of action for validating its therapeutic use as antibiotic potentiator importantly against MRSA and A. baumannii.

7-Geranyloxycinnamic Acid Isolated from Melicope lunu-ankenda Leaves Perturbs Colon Cancer and Breast Cancer Cell Lines' Growth via Induction of Apoptotic Pathway.

Globally, breast cancer is the most prevalent form of cancer in women and there is a need for alternative therapies such as plant-derived compounds with low systemic toxicity and selective toxicity to cancer cells. The aim of this study is to assess the cytotoxicity effects of 7-geranyloxycinnamic acid isolated from leaves of Melicope lunu-ankenda, a traditional medicinal plant, on the human breast cancer cell lines. Dried leaf powder was used for the preparation of different crude extracts using different solvents of increasing order of polarity. The structure of the isolated compound from the petroleum ether extract was elucidated by 1H and 13C NMR, LC-MS, and DIP-MS spectroscopy. The cytotoxic activity of the crude extract and 7-geranyloxycinnamic acid analyzed using MTT assay. Apoptotic analysis was evaluated using Annexin V-PI staining, AO/PI staining, intracellular ROS measurement, and measurement of activities of caspases 3/7, 8, and 9. Crude extracts and the isolated pure compound showed significant cytotoxicity against tested cancer cell lines. 7-geranyloxycinnamic acid was found to exert significant cytotoxic effects against breast cancer cell lines such as the MCF-7 and MDA-MB-231 cell lines. The cytotoxic effects are attributed to its ability to induce apoptosis via accumulation of ROS and activation of caspases in both breast cancer cell lines. The pure compound, 7-geranyloxycinnamic acid isolated from the leaves of M. lunu-ankenda, can exert significant cytotoxic effects against breast cancer cell lines without affecting the normal cells.

Isolation and Characterization of One New Natural Compound with Other Potential Bioactive Secondary Metabolites from Glycosmis cyanocarpa (Blume) Spreng. (Family: Rutaceae).

Glycosmis cyanocarpa (Blume) Spreng is a plant in the Rutaceae family and a species in the Glycosmis genus that has received little attention. Therefore, this research aimed to report the chemical and biological analysis of Glycosmis cyanocarpa (Blume) Spreng. The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study, and the structures of these metabolites were elucidated on the basis of a detailed analysis of NMR and HRESIMS spectroscopic data and by comparison with those of related compounds reported in the literature. Different partitions of the crude ethyl acetate (EtOAc) extract were evaluated for antioxidant, cytotoxic, and thrombolytic potentials. In chemical analysis, one new phenyl acetate derivative, namely 3,7,11,15-tetramethylhexadec-2-en-1-yl 2-phenylacetate (1), along with four known compounds N-methyl-3-(methylthio)-N-(2-phenylacetyl) acrylamide (2), penangin (3), ß-Caryophyllene oxide (4), and acyclic diterpene-phytol (5) were isolated for the first time from the stem and leaf of the plant. The ethyl acetate fraction showed significant free radical scavenging activity with an IC50 value of 11.536 µg/mL compared to standard ascorbic acid (4.816 µg/mL). In the thrombolytic assay, the dichloromethane fraction showed the maximum thrombolytic activity of 16.42% but was still insignificant compared to the standard streptokinase (65.98%). Finally, in a brine shrimp lethality bioassay, the LC50 values of dichloromethane, ethyl acetate, and aqueous fractions were found to be 0.687 µg/mL, 0.805 µg/mL, and 0.982 µg/mL which are significant compared to the standard vincristine sulfate of 0.272 µg/mL.

Coumarins from Rutaceae: Chemical diversity and biological activities.

Rutaceae is a family expressed by approximately 2100 species distributed in 154 genera widespread in tropical and temperate regions of Australasia, America, and South Africa. Substantial species of this family are employed as folk medicines. The literature describes the Rutaceae family as a great source of natural and bioactive compounds like terpenoids, flavonoids, and, especially, coumarins. To data, 655 coumarins were isolated and identified from Rutaceae in the past twelve years and, most of them, showed different biological and pharmacological activities. There are studies with coumarins from Rutaceae indicating that these compounds showed activity against cancer, inflammation, infectious diseases, and in the treatment of endocrinal and gastrointestinal conditions. Although coumarins are considered versatile bioactive molecules, until the present, there is no compiled information about coumarins from the Rutaceae family demonstrating the potency of these compounds in all dimensions and chemical similarities among the genera. The present review covers the relevant studies dealing with isolation of Rutaceae coumarins from 2010 until 2022 and outlines the current data on pharmacological activities these coumpounds. Additionally, the chemical disposition and similarity among Rutaceae genera are also statistically discussed employing PCA and HCA methods.

Coumarinolignoid and Indole Alkaloids from the Roots of the Hybrid Plant Citrus × paradisi Macfad (Rutaceae).

A phytochemical investigation of the roots of Citrus × paradisi Macfad. (Rutaceae) led to the isolation of two new compounds, namely 1-formyl-5-hydroxy-N-methylindolin-1-ium (1) and decyloxycleomiscosin D (2), along with ten known compounds: 1,1-dimethylpyrrolidin-1-ium-2-carboxylate (3), furan-2,3-diol (4), 5-methoxyseselin (5), umbelliferone (6), scopoletin (7), citracridone I (8), citracridone II (9), citracridone III (10), limonin (11) and lupeol (12). The structures were determined through the comprehensive spectroscopic analysis of 1D and 2D NMR and EI- and ESI-MS, as well as a comparison with the published data. Notably, compounds 3 and 4 from the genus Citrus are reported here for the first time. In addition, the MeOH extract of the roots and compounds 1-7 were screened against the human adenocarcinoma alveolar basal epithelial cell line A549 and the Caucasian prostate adenocarcinoma cell line PC3 using the MTT assay. While the extract showed significant activity, with IC50 values of 35.2 and 38.1 µg/mL, respectively, compounds 1-7 showed weak activity, with IC50 values of 99.2 to 250.2 µM and 99.5 to 192.7 µM, respectively.

Structurally diverse sulphur-containing amides from Glycosmis craibii with their potential antiproliferative activities.

Fourteen new sulphur-containing amides, glycocramides A-N (1-14), as well as nine known analogues (15-23) were isolated and characterized from Glycosmis craibii Tanaka. The chemical structures of new sulphur-containing amides 1-14 were ambiguously elucidated by extensive spectroscopic methods, while the known compounds 15-23 were identified by the comparison of their experimental spectral data with those described data in the literatures. The antiproliferative effects of all isolated sulphur-containing amides were evaluated in vitro. As a result, part of sulphur-containing amides showed remarkable inhibitory effects against MGC-803 cell line with IC50 values ranging from 13.12 ± 0.10 to 20.03 ± 0.13 µM. These research results suggest that the sulphur-containing amides are potentially to be developed as a new natural anti-tumor drugs.

Furoquinoline and bisindole alkaloids from the roots of Teclea nobilis and their in-silico molecular docking analysis.

Teclea nobilis is a medicinal plant widely used to treat oral pathogens, gonorrhea, fever, analgesics, asthma, joint pains, pneumonia, and intestinal worms in Ethiopia. Anticipated by these claims, column chromatographic separation of the roots extract of T. nobilis led to the isolation of eight alkaloids (1-8). The structures of the isolated compounds were identified based on their NMR (1D and 2D) spectral data analysis and comparison with reported literature data. In-silico molecular docking analysis of the isolated compounds were performed against Staphylococcus aureus DNA Gyrase (PDB ID: 2XCT) and human topoisomerase IIß DNA (PDB ID: 3QX3) by using AutoDock Vina. ADMET analysis were performed by SwissADME, PreADMET, and OSIRIS Property predictions. The study revealed that the isolated compounds exhibited promising binding affinity to DNA gyrase, especially with compound 5 forms a stable drug-protein complex. Whereas the ADME and drug-likeness analysis revealed that compound 5 is less absorbed from the gastrointestinal tract, crossblood brain barrier and a P-glycoprotein substrate. This indicated that compound 5 could be a good candidate as anticancer agent provided that in vivo analysis done for more confirmation.

Acrotrione B, a Prenylated and Highly Oxidized Xanthenoid with Antibacterial and Anti-proliferative Activities from the Roots of Acronychia pedunculata.

A new prenylated xanthenoid with a highly oxidized core, acrotrione B (1: ), together with six previously reported acetophenones (2:  - 7: ), were isolated from the roots of Acronychia pedunculata. The structures of the isolated compounds were elucidated by thorough analysis of their 1D and 2D NMR spectroscopic data. The relative and absolute configurations of acrotrione B were determined by electronic circular dichroism (ECD) calculations. Acrotrione B is an unusual, oxidized xanthenoid with a cyclohexadienone core that has not been previously reported. It thus represents a new skeletal type within the xanthenoid class. Acrotrione B (1: ) exhibited anti-proliferative activity against Hela (IC50 = 16.0 µM) and A549 (IC50 = 16.3 µM) cell lines. 5'-Prenylacrovestone (4: ) and acrovestone (5: ) were even more potent with IC50 values of 5.1 µM and 0.77 µM, respectively, against Hela cells and 11.8 µM and 1.13 µM, respectively, against A549 cells. Moreover, acrotrione B (1: ) displayed moderate antibacterial activities against Staphylococcus aureus, Bacillus cereus, and Bacillus subtilis, with MIC values in the range of 16 - 64 µg/mL. Finally, acropyrone (6: ) showed a significant suppression of lipopolysaccharide (LPS) induced NO production in murine macrophage J774.A1 cells (IC50 = 8.9 µM).

New flavone, and cytotoxicity activity of Rauia resinosa ethanolic extract and constituents.

The ethanolic extract from leaves of Rauia resinosa, Rutaceae, provided a new flavone, 5-hydroxy-5',6,7-trimethoxy-3',4'-methylenedioxyflavone (1), in addition to four known compounds: 3',4',5,5',7-pentamethoxyflavone (2), 5,7,8-trimethoxy-3'4'-methylenedioxyflavone (3), 3',4',5,7,8-pentamethoxyflavone (4) and ß-sitosterol (5). The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR, UPLC-DAD-MS and UPLC-ESI-MS/MS, involving comparison with literature data. Cytotoxicity of leaves and stems extracts, their fractions and compounds (2), (3), (4) and (5) were evaluated against T24 (bladder carcinoma), TOV-21-G (ovarian adenocarcinoma) and HepG2 (liver carcinoma) cell lines.

Acronyrones A-C, unusual prenylated acetophenones from Acronychia pedunculata.

Two novel prenylated acetophenones with new carbon skeletons, acronyrones A and B (1 and 2), and a new analogue, acronyrone C (3), together with two known compounds (4 and 5) were isolated from the leaves of Acronychia pedunculata. Their structures with absolute configurations were identified by interpretation of spectroscopic data, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first example of prenylated acetophenones possessed a C7 (1) and a C6 (2) side chain, forming a 4-isobutylchroman-2-one unit and a 3-(2-methylpropylidene)benzofuran-2(3H)-one moiety with the acetophenone core, respectively. In addition, compound 4 exhibited significant dose-dependent transcriptional activation effect against retinoid X receptor-α (RXRα), and could be regarded as a new type of non-classical RXR ligand.

Isolation, Characterization and Pharmacological Investigations of a New Phenolic Compound along with Four Others Firstly Reported Phytochemicals from Glycosmis cyanocarpa (Blume) Spreng.

Plants are serving the mankind with important bioactive phytochemicals from the very ancient ages to develop novel therapeutics against different disease states. Glycosmis cyanocarpa (Blume) Spreng is a plant from the Rutaceae family and a very less explored species from the Glycosmis genus. Thus, this present study was intended to present the chemical and biological investigation of Glycosmis cyanocarpa (Blume) Spreng. The chemical investigation resulted in the isolation of one new phenolic compound to the best of our knowledge which is (4-(3-hydroxy-2-methylpropyl)-2-methoxyphenol) (1) along with four known compounds that are isolated for the first time from this species- 3-methyl-1H-indole (2), Tri-transpoly-cis prenol-12 (3), Stigmasterol (4) and ß-sitosterol (5). Their chemical structures were elucidated based on extensive spectroscopic methods, including 1D and 2D NMR, and comparison with the available literature data. Isolated phytochemicals were further investigated to unveil their antioxidant properties with IC50 values (ranged from 9.97-75.48 µg/mL), cytotoxicity with LC50 values (ranged from 1.02-1.92 µg/mL), and antibacterial properties against some selected Gram (+) ve and Gram (-) ve bacteria. Among the compounds, 3-methyl-1H-indole (2) was found to be the most active against Staphylococcus aureus. Moreover, the phenolic compound (1) and the alkaloid (2) revealed the highest antioxidant (9.97 µg/mL) and cytotoxic activities (1.02 µg/mL), respectively. Thus, the isolation of these bioactive phytochemicals from the plant revealed a new perception in the study arena of drug discovery and the findings may ease the development and discovery of novel therapeutics. Further investigations are still recommended to understand their exact molecular mechanism and toxicological impact.

Anti-inflammatory constituents from the stems and leaves of Glycosmis ovoidea Pierre.

Seven undescribed compounds, including four acridones, two coumarins, and a phenylpropanoid, together with 13 known acridone analogues were isolated from the ethanolic extract of the stems and leaves of Glycosmis ovoidea Pierre. Their structures were elucidated on the basis of comprehensive analysis of 1D and 2D NMR and HRESIMS spectroscopic data, and the absolute configurations were assigned by comparison of the experimental and calculated ECD data. Five compounds showed moderate inhibitory effects on nitric oxide production stimulated by lipopolysaccharide in BV-2 microglial cells with IC50 values in the range of 18.30-30.84 µM, and three compounds showed potent inhibition on 5-lipoxygenase (5-LOX) with IC50 values in the range of 2.08-10.26 µM. The possible binding sites of the active compounds with 5-LOX were further performed by molecular docking.

Larvicidal Activity of Two Rutaceae Plant Essential Oils and Their Constituents Against Aedes albopictus (Diptera: Culicidae) in Multiple Formulations.

Aedes albopictus (Skuse) is a vector of several arboviruses, such as dengue, chikungunya, West Nile, and Zika viruses. At present, the use of synthetic insecticides is the main vector control strategy. However, the widespread and long-term use of insecticides has aroused several problems, including insecticide resistance, environmental pollution, and non-target species effects, thereby encouraging researchers to search for new alternatives derived from natural products. In recent decades, essential oils (EOs) as natural alternatives to control mosquitoes have received increasing attention. In the initial larvicidal activity screen, two Rutaceae plants (Citrus aurantium and Citrus paradisi) EOs were selected and evaluated for killing Ae. albopictus larvae. The LC50 values of C. aurantium and C. paradisi EOs against Ae. albopictus were 91.7 and 100.9 ppm, respectively. The main components of C. aurantium EO include diethyl o-phthalate (37.32%), limonene (10.04%), and methyl dihydrojasmonate (6.48%). The main components of C. paradisi EO include limonene (60.51%), diethyl o-phthalate (11.75%), linalool (7.90%), and styralyl acetate (6.28%). Among these main components of the two EOs, limonene showed potent larvicidal activity, with the LC50 value of 39.7 ppm. The nanoemulsions of limonene were prepared and characterized. The duration of larvicidal activity was greater in the limonene nanoemulsions than when limonene was applied in solvent. This study demonstrates that EOs of plants in family Rutaceae are a potential resource to develop new larvicides, and nanoemulsification is an effective method for improving the physicochemical properties and efficacy of natural products as larvicides.

Determination of quality markers for quality control of Zanthoxylum nitidum using ultra-performance liquid chromatography coupled with near infrared spectroscopy.

With the increasing demand for quality control in the traditional Chinese medicine industry, there is a need for the development of quality markers and a quick, non-destructive technique for the discrimination of related species. In our previous study, ultra-performance liquid chromatography (UPLC) was used for the simultaneous determination of five compounds, including three alkaloids (nitidine chloride, chelerythrine, and magnoflorine), one flavonoid (aurantiamarin), and one lignan (sesamin). In this study, the simultaneous quantification of the above-mentioned compounds could be used to discriminate the powders of roots from those of stems. To further test the reliability of the five compounds, seventy-two batches of wild and seventy-five batches of cultivated Zanthoxylum nitidum samples collected from Guangdong, Guangxi, and Fujian provinces in China were analyzed by UPLC and near-infrared spectroscopy (NIRS). In general, the quantitative results of UPLC were consistent with those of NIRS, and cultivated Z. nitidum has similar major bioactive compounds as the wild one, as supported by principal component analysis. Consequently, these five major bioactive compounds are suggested as potential quality markers. In addition, the NIRS method with discriminant analysis successfully differentiated Z. nitidum from three related species (Z. avicennae, Z. scandens and Toddalia asiatica) of the Rutaceae family. In summary, this study provides a method for the rapid identification of Z. nitidum and discrimination of root and stem powders, and suggests five compounds as quality markers for the evaluation of Z. nitidum.

Chemical Constituents of the Stem Bark of the Hybrid Plant Citrus × paradisi Macfad. (Rutaceae).

The stem bark of Citrus × paradisi Macfad. (Rutaceae) gave (23S)-isolimonexic acid (1), limonin (2), citracridone II (3), citpressine II (4), citpressine I (5), grandisine (6), 2-hydroxynoracronycine (7), citracridone I (8), 5-methoxyseselin (9), umbelliferone (10), scopoletin (11), naringenin (12), apigenin (13), friedelin (14), agrostophyllinone (15) and stigmasterol-3-O-ß-D-glucopyranoside (16). The structures of the compounds were determined using NMR and MS spectroscopic data, and by comparison with published data. The relative configuration of 1 was proposed as (23S)-isolimonexic acid using NOE studies. Hydrogenation reaction of compound 3 led to the new derivative 3',4'-dihydrocitracridone II (3a). Cytotoxicity activities against the human adenocarcinoma alveolar basal epithelial cell lines A549 and the Caucasian prostate adenocarcinoma cell lines PC3, using the MTT assays showed that the methanol crude extract was significant with IC50 values of 30.1 and 31.7 µg/mL, respectively, with the positive control, doxorubicin giving an IC50 of 0.9 µM. In addition, compounds 3, 7 and 8 gave moderate cytotoxic activities with IC50 values of 33.1, 31.2 and 32.5 µM for A549 cells and 35.7, 33.8 and 34.9 µM for PC3 cells, respectively. The hydrogenated 3a was less active than 3, suggesting that the presence of the double bond in pyrans is important for structure-activity relationship.