Sustainable Natural Resources for Aphid Management: ß-Ionone and Its Derivatives as Promising Ecofriendly Botanical-Based Products.

ß-Ionone, sustainably derived from Petunia hybrida as a natural bioresource, was identified as a lead compound for integrated aphid management. A series of ß-ionone derivatives containing ester groups were designed and synthesized for the purpose of discovering renewable botanical-based products. The odorant-binding protein (OBP) binding test indicated that ß-ionone and its derivatives displayed binding affinities with Acyrthosiphon pisum OBP9 (ApisOBP9) and Harmonia axyridis OBP15 (HaxyOBP15). Bioactivity assays revealed that most ß-ionone derivatives exhibited a higher repellent activity than that of ß-ionone. ß-Ionone and derivatives 4g and 4l displayed attractiveness to H. axyridis. Specifically, 4g was a highly promising derivative, possessing good repellent activity against A. pisum and attractiveness to H. axyridis. Molecular dynamics simulations revealed that integrating the hydrophobic ester group into the ß-ionone framework strengthened the van der Waals interactions of 4g with ApisOBP9/HaxyOBP15, improving the binding affinity with OBPs and producing higher push-pull activity than ß-ionone; 4g also had low toxicity toward nontarget organisms. Thus, 4g is a potential ecofriendly, botanical-based option for aphid management.

ß-Ionone enhances the inhibitory effects of 5-fluorouracil on the proliferation of gastric adenocarcinoma cells by the GSK-3ß signaling pathway.

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.

ß-ionone inhibits the grazing of Daphnia sinensis by reducing the activity of acetylcholinesterase.

ß-ionone is a volatile metabolite of Microcystis aeruginosa that is toxic to aquatic organisms. Using Daphnia sinensis as model, our present study found that ß-ionone could significantly reduce heart rate and feeding rate, and induce intestinal emptying. Transcriptomic analysis showed that ß-ionone could significantly inhibit the expression of acetylcholinesterase (AchE) mRNA, while metabolomics further revealed that ß-ionone could significantly increase the level of acetylcholine (Ach) in D. sinensis. These results indicated that ß-ionone might act as an AchE inhibitor, resulting in an increase in Ach levels. To test this hypothesis, both in vivo and in vitro experiments demonstrated that ß-ionone could significantly reduce AchE activity. Furthermore, the inhibitory effects of ß-ionone on heart rate and feeding rate could be blocked by the M-type Ach receptor (mAchR) blocker. These findings confirm that ß-ionone is a novel AchE inhibitor. ß-ionone could inhibit the activity of AchE, which in turn resulted in an increase of Ach in D. sinensis. Consequently, elevated levels of Ach could suppress the heart rate and feeding rate of D. sinensis by activating the mAchR, while concurrently accelerating the rate of intestinal emptying by stimulating intestinal peristalsis, thereby obstructing the digestion of algae within the intestinal tract.

A Food Odorant, α-Ionone, Inhibits Skin Cancer Tumorigenesis by Activation of OR10A6.

SCOPE: This study aims to investigate the anticancer properties of α-ionone in squamous cell carcinoma (SCC). METHODS AND RESULTS: The expression of OR10A6 together with olfactory receptor signaling components is demonstrated in A431 human SCC cells via RT-PCR and qRT-PCR analysis. OR10A6 activation in A431 cells using the ligand α-ionone inhibits proliferation and migration but induces apoptosis which is confirmed by proliferation assay, colony formation, and western blotting. The mechanism involves the core proteins of the Hippo pathway, where the phosphorylation of large tumor suppressor kinase (LATS), yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) is confirmed by western blotting. However, the anticancer effects of α-ionone are abrogated in A431 cells with OR10A6 gene knockdown. In A431 xenograft mouse model, the injection of α-ionone suppresses tumor growth, induces apoptosis, and increases phosphorylation of the LATS-YAP-TAZ signaling axis in the Hippo pathway. None of these effects are observed in xenografted tumors with OR10A6 gene knockdown. CONCLUSION: These findings collectively demonstrate that activation of ectopic OR OR10A6 by α-ionone in SCC cells stimulates the Hippo pathway and suppresses tumorigenesis both in vitro and in vivo, suggesting a novel therapeutic candidate for the treatment of SCC.

Megastigmane glycosides from the traditional Uighur medicine Cydonia oblonga Mill.

Phytochemical investigation on the fruits of Cydonia oblonga Mill., a traditional Uighur medicine, led to the isolation of seven undescribed and nine known megastigmane glycosides. Their structures including absolute configurations were characterized by an extensive analysis of spectroscopic data including HRESIMS and NMR, combined with ECD calculations. Additionally, compounds 1, 2, 4, and 6-16 exhibited anti-inflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6 in RAW264.7 cells induced by lipopolysaccharides (LPS) with inhibitory rates of 10.79%-44.58% at 20 µM.

Three New Ionone Glycosides from Rhododendron capitatum Maxim.

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

The effect of ß-ionone on bacterial cells: the use of specific lux-biosensors.

The diversity of the biological activity of volatile organic compounds (VOCs), including unsaturated ketone ß-ionone, promising pharmacological, biotechnological, and agricultural agent, has aroused considerable interest. However, the functional role and mechanisms of action of VOCs remain insufficiently studied. In this work, the response of bacterial cells to the action of ß-ionone was studied using specific bioluminescent lux-biosensors containing stress-sensitive promoters. We determined that in Escherichia coli cells, ß-ionone induces oxidative stress (PkatG and Pdps promoters) through a specific response mediated by the OxyR/OxyS regulon, but not SoxR/SoxS (PsoxS promoter). It has been shown that ß-ionone at high concentrations (50 µM and above) causes a weak induction of the expression from the PibpA promoter and slightly induces the PcolD promoter in the E. coli biosensors; the observed effect is enhanced in the ΔoxyR mutants. This indicates the presence of some damage to proteins and DNA. ß-Ionone was found to inhibit the bichaperone-dependent DnaKJE-ClpB refolding of heat-inactivated bacterial luciferase in E. coli wild-type and ΔibpB mutant strains. In the cells of the Gram-positive bacterium Bacillus subtilis 168 pNK-MrgA ß-ionone does not cause oxidative stress. Thus, in this work, the specificity of bacterial cell stress responses to the action of ß-ionone was shown.

Effects of natural Ionones and derived novel analogues with simplified structures on behavioral responses of whiteflies.

BACKGROUND: Whiteflies are major pests in agriculture, causing damage to crops and transmitting plant viruses. Using Volatile Organic Compounds (VOCs) as semiochemicals offers a sustainable approach for combating whiteflies. One such group of compounds, represented by ß-ionone, has been found to possess repellent/attractant properties. To further explore the behavioral effects of these compounds on whiteflies, we selected five natural ionone compounds and synthesized six novel analogues to examine the impact of structural variations on whitefly behavior. RESULTS: Our results demonstrated that ß-ionone and its analogues have a significant impact on the behavior of whiteflies. Among them, 0.01% pseudo ionone solution exhibited an attractant effect on whiteflies. Notably, the application of 1% ß-ionone and 0.1% ß-ionol solution demonstrated a notable repellent effect and oviposition deterrent effect on whitefly. We also found that the novel ionone analogue (±)1A exhibited a strong repellent effect. Both ß-ionol and compound (±)1A possess high logP values and low saturation vapor pressures, which contribute to enhanced lipophilicity, making them more likely to penetrate insect antennae and prolong their presence in the air. CONCLUSION: The newly discovered ionone analogue (±)1A and ß-ionol exhibit improved repellent effects, while pseudo ionone shows an attractant effect. These three compounds hold promising potential for development as novel biological control agents. Our work highlights the efficacy of VOCs as a protection method against whiteflies. These findings indicate that our new technology for a 'push-pull' control method of B. tabaci can offer a novel tool for integrated pest management (IPM). © 2024 Society of Chemical Industry.

A new megastigmane glycoside, a new organic acid glycoside and other constituents with anticomplementary activity from Artemisia halodendron.

A new megastigmane glycoside, (1R,5R,6S,7E)-megastigman-3,9-dione-7-en-6,11-diol 11-O-ß-D-glucopyranoside (1), and a new organic acid glycoside, methyl (4 R)-4-O-ß-D-glucopyranosyl-decanoate (2), together with eight known compounds (3-10), were isolated from the aerial parts of Artemisia halodendron Turcz. ex Bess. (Asteraceae). Their chemical structures were elucidated by 1 D and 2 D NMR and HR-ESI-MS spectra and DP4+ probability analysis. Among the identified compounds, compounds 5, 6 and 10 were isolated from the family Asteraceae, and compounds 3, 4 and 7-9 were identified from the genus Artemisia for the first time. All of the compounds were evaluated for their anticomplementary activity against the classical pathway (CP) and the alternative pathway (AP). Compounds 7 and 9 showed anticomplementary activity with the CH50 values of 0.31 ± 0.08 and 0.50 ± 0.09 mM, respectively.

New Ionone Glycosides from the Aerial Parts of Allium sativum and Their Anti-Platelet Aggregation Activity.

The bulbs of Allium sativum known as garlic are widely used as food or seasoning. In China they have been used as a traditional Chinese medicine (TCM) since ancient times for the treatment of scabies, tuberculosis, pertussis, diarrhea and dysentery. A. sativum has reportedly shown platelet aggregation inhibition and has been used in the treatment of cardiovascular diseases. However, there are only few studies focussing on the aerial parts, which are normally discarded during harvest. In this study, two new ionone glycosides, dasuanxinosides D and E (1, 2: ), are isolated from the aerial parts together with 13 known compounds including alkanes derivatives and alkyl glycosides (3 - 15: ), which are reported for the first time from this plant. Their structures are identified by extensive NMR and HRMS analyses. The isolated compounds are evaluated for their inhibitory effect on adenosine diphosphate (ADP)-induced platelet aggregation in vitro.

Megastigmane sesquiterpenoids from whole plants of Viola kunawurensis.

Investigation on the chemical constituents of Viola kunawurensis resulted in the isolation of seven undescribed megastigmane sesquiterpenoids including four bicyclic megastigmane glucosides, kunawuronoside A-D, two megastigmane glucosides, kunawuronoside E-F, and a megastigmane, kunawurone A, together with ten known megastigmane sesquiterpenoids. Their structures were established by comprehensive 1D, 2D-NMR and HRESIMS analyses, and their absolute configurations were determined by comparing their calculated ECD data with the experimental ones. Evaluations of the anti-inflammatory activity revealed that kunawuronoside A-D and compounds 14-15 inhibited COX-2 expression with inhibition rates ranging from 36.7% to 58.5%, while the NO production induced by lipopolysaccharide (LPS) was suppressed by the kunawuronoside A-D in a dose-dependent manner in RAW264.7 macrophage cell line.

Chemotherapeutic potentials of ß-ionone against Trypanosoma congolense infection: Inhibition of parasite proliferation, anemia development, trans-sialidase (TconTS3 and TconTS4) gene expressions, and phospholipase A2.

Trypanosoma congolense is a pathogenic African animal trypanosome species causing devastating conditions leading to death of an infected host. The drawbacks of the existing trypanocidal drugs have led to the search for new drug candidates. In this study, ß-ionone at 15 and 30 mg/kg body weight (BW) was orally administered to T. congolense infected rats for 14 days followed by an assessment of anemia, organ damages, and the expression of T. congolense trans-sialidase gene variants. A significant decrease in parasitemia (p < .05) was observed in the animals treated with 15 mg/kg BW ß-ionone besides increased animal survival rate. A trypanosome-induced decrease in packed cell volume (PCV) and histopathological changes across tissues was significantly (p < .05) ameliorated following treatment with both doses of ß-ionone. This is in addition to reversing the parasite-induced upsurge in free serum sialic acid (FSA) and expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3, and TconTS4). Correlation analysis revealed a positive correlation (p > .05) between FSA with the TconTS gene expressions. In addition, the compound inhibited partially purified T. congolense sialidase and phospholipase A2 via mixed inhibition pattern with inhibition binding constants of 25.325 and 4.550 µM, respectively, while molecular docking predicted binding energies of -5.6 kcal/mol for both enzymes. In conclusion, treatment with ß-ionone suppressed T. congolense proliferation and protected the animals against some of the parasite-induced pathologies whilst the effect on anemia development might be due to inhibition of sialidase and PLA2 activities as well as the expression levels of TconTS3 and TconTS4.

Evaluation of the antifungal activity of α, ß, and δ-damascone and inclusion complexes in ß-cyclodextrin against Candida spp.

Due to the increase in fungal resistance to existing drugs, a need exists to search for new antifungals. This study aimed to evaluate the antifungal activity of α, ß, and δ-damascone and inclusion complexes with ß-cyclodextrin against different Candida spp. The inclusion complex of ß-damascone was prepared by the co-evaporation method using three molar proportions (1:1; 2:1; 3:1 (ßDA-ßCD)) and analyzed using Fourier transform infrared spectroscopy (FTIR). Standard Candida albicans (CA INCQS 40,006), Candida krusei (CK INCQS 40,095), and Candida tropicalis (CT INCQS 40,042) strains were used to evaluate antifungal activity. The substances were tested individually or in association with fluconazole (FCZ). The IC50 and cell viability curve constructions were performed using the microdilution method. The minimum fungicidal concentration (MFC) was determined by the subculture method in a solid medium. The α, ß, and δ-DA isolated or in combination with fluconazole (FCZ) showed significant antifungal activity. ß-damascone showed effective complexation in the three molar proportions assayed; however, none of the inclusion complexes was demonstrated clinically significant effects against the fungal tested. Then, all compounds have shown promising antifungal activities; however, in vivo assays are necessary to have therapeutical application in the future.

Chemical characterization, antiproliferative and antifungal activities of Clinacanthus nutans.

Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1-32), including three new megastigmanes (1-3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 µM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.

Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.

ß-Ionone Attenuates Dexamethasone-Induced Suppression of Collagen and Hyaluronic Acid Synthesis in Human Dermal Fibroblasts.

Stress is a major contributing factor of skin aging, which is clinically characterized by wrinkles, loss of elasticity, and dryness. In particular, glucocorticoids are generally considered key hormones for promoting stress-induced skin aging through binding to glucocorticoid receptors (GRs). In this work, we aimed to investigate whether ß-ionone (a compound occurring in various foods such as carrots and almonds) attenuates dexamethasone-induced suppression of collagen and hyaluronic acid synthesis in human dermal fibroblasts, and to explore the mechanisms involved. We found that ß-ionone promoted collagen production dose-dependently and increased mRNA expression levels, including collagen type I α 1 chain (COL1A1) and COL1A2 in dexamethasone-treated human dermal fibroblasts. It also raised hyaluronic acid synthase mRNA expression and hyaluronic acid levels. Notably, ß-ionone inhibited cortisol binding to GR, subsequent dexamethasone-induced GR signaling, and the expression of several GR target genes. Our results reveal the strong potential of ß-ionone for preventing stress-induced skin aging and suggest that its effects are related to the inhibition of GR signaling in human dermal fibroblasts.

Discovery of Antimetastatic Chiral Ionone Alkaloid Derivatives Targeting HIF-1α/VEGF/VEGFR2 Pathway.

Novel chiral ionone alkaloid derivatives were synthesized and their antimetastatic effects were evaluated in human breast cancer cells using chemotaxis assay. Compared with positive control LY294002, a PI3 K inhibitor, derivatives 10 a, 11 a, 11 c, 11 g, 11 j, 11 k and 11 w exhibited significant inhibitory effects against cancer cell migration. Especially, the IC50 for compound 11 g was as low as 0.035±0.004 µM. Further investigations on compound 11 g revealed that it could exert inhibitory effects on the adhesion, migration and invasion of MDA-MB-231 cells. The mechanisms for the antitumor metastatic effects of 11 g might be through the inhibition of HIF-1α/VEGF/VEGFR2/Akt pathway, which suppressed the downstream signaling molecules, including Akt1/mTOR/p70S6K and Akt2/PKCζ/integrin ß1 pathways. Taken together, chiral ionone alkaloid derivative 11 g has the potential to be developed into an antitumor metastatic agent for breast cancer.

Ionone Is More than a Violet's Fragrance: A Review.

The term ionone is derived from "iona" (Greek for violet) which refers to the violet scent and "ketone" due to its structure. Ionones can either be chemically synthesized or endogenously produced via asymmetric cleavage of ß-carotene by ß-carotene oxygenase 2 (BCO2). We recently proposed a possible metabolic pathway for the conversion of α-and ß-pinene into α-and ß-ionone. The differences between BCO1 and BCO2 suggest a unique physiological role of BCO2; implying that ß-ionone (one of BCO2 products) is involved in a prospective biological function. This review focuses on the effects of ionones and the postulated mechanisms or signaling cascades involved mediating these effects. ß-Ionone, whether of an endogenous or exogenous origin possesses a range of pharmacological effects including anticancer, chemopreventive, cancer promoting, melanogenesis, anti-inflammatory and antimicrobial actions. ß-Ionone mediates these effects via activation of olfactory receptor (OR51E2) and regulation of the activity or expression of cell cycle regulatory proteins, pro-apoptotic and anti-apoptotic proteins, HMG-CoA reductase and pro-inflammatory mediators. α-Ionone and ß-ionone derivatives exhibit anti-inflammatory, antimicrobial and anticancer effects, however the corresponding structure activity relationships are still inconclusive. Overall, data demonstrates that ionone is a promising scaffold for cancer, inflammation and infectious disease research and thus is more than simply a violet's fragrance.

Antioxidant compounds from Banisteriopsis argyrophylla leaves as α-amylase, α-glucosidase, lipase, and glycation inhibitors.

Banisteriopsis argyrophylla belongs to the Malpighiaceae family, which is a species from Cerrado, also known as "cipó-prata" or "cipó-folha-de-prata." Several species of this family present biological potential. This work reports the chemical identification of the ethanol extract (EE) and its fractions from B. argyrophylla leaves and shows the analysis of the antioxidant activity and inhibitory effects on activities of α-amylase, α-glucosidase and lipase, and non-enzymatic glycation. The ethyl acetate fraction (EAF) and n-butanol fraction (BF) showed antioxidant activity, with IC50 values of 4.1 ± 0.1 and 4.8 ± 0.1 µg mL-1, respectively, by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and IC50 values of 6046.3 ± 174.2 and 6264.2 ± 32.2 µmol Trolox eq g-1 by the oxygen radical absorbance capacity (ORAC) method. Furthermore, the DPPH method with these fractions presented electroactive species with antioxidant potential, as shown by the differential pulse voltammetry (DPV) method. The inhibitory effects of the EAF and BF were demonstrated by the following results: IC50 of 5.1 ± 0.3 and 2.5 ± 0.2 µg mL-1 for α-amylase, IC50 of 1093.5 ± 26.0 and 1250.8 ± 21.9 µg mL-1 for α-glucosidase, IC50 of 8.3 ± 4.1 and 4.4 ± 1.0 µg mL-1 for lipase, and IC50 of 1.3 ± 0.1 and 0.9 ± 0.1 µg mL-1 for glycation. Some bioactive compounds were identified by (-)-ESI-MS/MS, such as catechin, procyanidins, glycosylated flavonoids, kaempferol, and megastigmane glucosides. The antidiabetic activity of B.argyrophylla has been reported for the first time.

Synthesis and biological evaluation of ß-ionone oriented proapoptosis agents by enhancing the ROS generation.

ß-ionone, a cyclic terpenoid compound present in many fruits, has been showed a broad spectrum of biological activities. In this paper, we synthesized a panel of ß-ionone derivatives and tested their anti-proliferation activity on cancer cell by the MTT assay. The results showed that most of the ß-ionone derivatives were more active than ß-ionone and curcumin. Particularly, the ß-ionone derivatives (1a, 1d and 1g) with ortho-substituents on the aromatic ring exhibited much stronger cytotoxicity than their corresponding meta- and para-substituted compounds. Importantly, the cytotoxicity of the ß-ionone derivatives (1a, 1d and 1g) were relationship with their reactive oxygen species (ROS)-generation abilities, which could lead to the redox imbalance, lipid peroxidation, the loss of mitochondrial membrane potential (MMP), the activation of Bax and Caspase 3, followed by cell apoptosis. This work suggest that the "ortho effect", the ROS-generation ability and drawing fluorine atom into drugs may play a potent role in enhancing the anticancer activity of ß-ionone derivatives.