Β-unsaturated Carbonyl Group Research Articles

Apo-12′-capsorubinal exhibits anti-inflammatory effects and activates nuclear factor erythroid 2-related factor 2 in RAW264.7 macrophages

Apocarotenoids have short carbon chain structures cleaved at a polyene-conjugated double bond. They can be biosynthesized in plants and microorganisms. Animals ingest carotenoids through food and then metabolize them into apocarotenoids. Although several apocarotenoids have been identified in the body, their precise health functions are still poorly understood. This study investigated the anti-inflammatory activities of apo-12′-capsorubinal in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. It was confirmed that apo-12′-capsorubinal was not cytotoxic to the macrophages at the concentrations tested. Apo-12′-capsorubinal treatment led to a marked downregulation of interleukin (IL)-6 protein and Il6 mRNA levels. This apocarotenoid exhibited more potent inhibitory effects than its parent carotenoids, capsanthin and capsorubin. Furthermore, apo-12′-capsorubinal, but not its parent carotenoids, promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-target genes, such as heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), in a dose-dependent manner. Furthermore, a comparison using apo-12′-zeaxanthinal and 7,8-dihydro-8-oxo-apo-12′-zeaxanthinal revealed that the α, β-unsaturated carbonyl group on the polyene linear chain mediated the enhanced nuclear Nrf2 translocation, HO-1 expression, and inhibition of IL-6 production. In contrast, apo-12′-mytiloxanthinal, which harbored a hydroxyl group at C-8 of apo-12′-capsorubinal, did not exhibit any of these activities. These results indicated that the β carbon of the α, β-unsaturated carbonyl group in the linear part of the polyene chain is crucial to the Nrf2-activating and anti-inflammatory effects of apo-12′-capsorubinal. This study will advance our knowledge of the physiological significance of xanthophyll-derived apocarotenoids and their potential use as nutraceuticals and pharmaceuticals.

Selective hydrodeoxygenation of α, β-unsaturated carbonyl compounds to alkenes

Achieving selective hydrodeoxygenation of α, β-unsaturated carbonyl groups to alkenes poses a substantial challenge due to the presence of multiple functional groups. In this study, we develop a ZnNC-X catalyst (X represents the calcination temperature) that incorporates both Lewis acidic-basic sites and Zn-Nx sites to address this challenge. Among the catalyst variants, ZnNC-900 catalyst exhibits impressive selectivity for alkenes in the hydrodeoxygenation of α, β-unsaturated carbonyl compounds, achieving up to 94.8% selectivity. Through comprehensive mechanism investigations and catalyst characterization, we identify the Lewis acidic-basic sites as responsible for the selective hydrogenation of C=O bonds, while the Zn-Nx sites facilitate the subsequent selective hydrodeoxygenation step. Furthermore, ZnNC-900 catalyst displays broad applicability across a diverse range of unsaturated carbonyl compounds. These findings not only offer valuable insights into the design of effective catalysts for controlling alkene selectivity but also extend the scope of sustainable transformations in synthetic chemistry.

Novel sulfonyl-substituted tetrandrine derivatives for colon cancer treatment by inducing mitochondrial apoptosis and inhibiting PI3K/AKT/mTOR pathway

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, β-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.

A COMPREHENSIVE REVIEW ON CHALCONE ANALOGUES-VERSATILE SCAFFOLD WITH MEDICINAL AND BIOLOGICAL POTENTIAL

This review’s main focus is on the most recent synthesis of chalcones with N, O, or S heterocycles, highlighting their biological potential. Chalcone derivatives are considered in beneficial species because they possess a keto-ethylenic moiety, CO−CH=CH−. Due to the existence of a reactive α, β-unsaturated carbonyl group, the synthesis of chalcone derivatives, which have been physiologically explored for use against specific disease targets, has been made possible by recent advances in heterocyclic chemistry. The need for novel drugs that are effective against multidrug-resistant pathogens has been driven by the growth in antibiotic resistance brought on by a variety of reasons. Chalcones are phenolic compounds that fall within the flavonoids category. They are a part of a large category of naturally occurring bioactive substances. During this review we have gone through a number of studies where chalcones were created via Claisen Schmidt condensation of suitable acetophenone with suitable aromatic aldehydes in the presence of an aqueous solution of potassium hydroxide and ethanol at room temperature in an effort to create antibacterial agents. The review content have been obtained through web browsing on various scientific databases and search engines like Science Direct, Pub Med, Research Gate, Google Scholar, etc. The synthesis of diverse chalcone derivatives was motivated by the potential activity of naturally occurring chalcones as anticancer, anti-inflammatory, antibacterial, antioxidant, and antiparasitic characteristics, as well as by their unique chemical structural structure. Flavonoids and isoflavonoids, which are frequent chemical building blocks found in a variety of naturally derived compounds, are enhanced by chalcone. This review may prove to be helpful for the creation and design of new powerful therapeutic medications.

MAO-B Inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a Neuroprotective Agent Against Alzheimer's Disease.

Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1-IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD.

Chemistry and synthetic methodologies of chalcones and their derivatives: A review

Due to the presence of keto ethylenic moiety, CO-CH=CH-, the chalcones and their derivatives are considered valuable moieties in the field of heterocyclic and synthetic organic chemistry. Chalcones and their derivatives have a wide range of antiproliferative, antifungal, antibacterial, antiviral, antileishmanial and antimalarial pharmacological activities because they contain a reactive α, β-unsaturated carbonyl group. Chalcones are also isolated from natural resources, especially from Piper methysticum as flavonoids and polyphenolic compounds. These derivatives are synthesized by using various conventional and greener approaches by employing different means of reactions, frequently by using Claisen-Schmidt condensation. In this review, information on the various synthetic methodologies, various approaches and techniques for the synthesis of chalcones and their derivatives are described. Thus, it will be useful to design and develop new novel drug-like candidates in the field of medicine.

Biological evaluation of polycyclic chalcone based acrylamides in human MCF-7 and HeLa cancer cell lines

Breast and cervical cancer account for the majority of cancer-narrated fatalities among women worldwide, necessitating the development of novel, effective therapeutic ways to combat the disease. In this study, we synthesized 6-methoxy naphthalene and anthracene-based acrylamide chalcone (NBA and ABA) and evaluated its activity for cell multiplication inhibition against two cancer cell lines from humans such as MCF-7 (Human Breast) and HeLa (Cervical) by MTT assay. Physiochemical characterization, such as FT-IR and NMR analyses, validated the synthesized NBA and ABA. Both NBA and ABA have shown antiproliferative action against two cancer cell lines, each with IC50 values of 38.46 and 48.25 μg/mL for HeLa cells and 38.02 and 36.35 μg/mL for MCF-7 cell lines. The results suggest that these acrylamide chalcones for cancer therapy at the lowest concentration. NBA and ABA could prevent cervical and breast cancer in-vitro, and their anti-cancer activity was closely related to methoxy-substituted naphthalene, anthracene ring, α, β-unsaturated carbonyl and amide group. According to docking data, the NBA and ABA have dock scores ranging from −8.7 to −11.44 kcal/mol. The highest dock score for compound ABA was −11.58 kcal/mol and compound NBA was −10.77 kcal/mol with Braf (5VAM) binding site.

The Structure Basis of Phytochemicals as Metabolic Signals for Combating Obesity.

The consumption of phytochemicals, bioactive compounds in fruits and vegetables, has been demonstrated to ameliorate obesity and related metabolic symptoms by regulating specific metabolic pathways. This review summarizes the progress made in our understanding of the potential of phytochemicals as metabolic signals: we discuss herein selected molecular mechanisms which are involved in the occurrence of obesity that may be regulated by phytochemicals. The focus of our review highlights the regulation of transcription factors toll like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), the peroxisome proliferator-activated receptors (PPARs), fat mass and obesity-associated protein (FTO) and regulation of microRNAs (miRNA). In this review, the effect of phytochemicals on signaling pathways involved in obesity were discussed on the basis of their chemical structure, suggesting molecular mechanisms for how phytochemicals may impact these signaling pathways. For example, compounds with an isothiocyanate group or an α, β-unsaturated carbonyl group may interact with the TLR4 signaling pathway. Regarding Nrf2, we examine compounds possessing an α, β-unsaturated carbonyl group which binds covalently with the cysteine thiols of Keap1. Additionally, phytochemical activation of PPARs, FTO and miRNAs were summarized. This information may be of value to better understand how specific phytochemicals interact with specific signaling pathways and help guide the development of new drugs to combat obesity and related metabolic diseases.

Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation.

Tranilast (TRL), a synthetic derivative of a tryptophan metabolite, is an anti-allergic drug used to treat bronchial asthma. We investigated how TRL activated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1) pathway based on the electrophilic chemistry of the drug and whether TRL activity contributed to the treatment of rat colitis. In human colon carcinoma cells, TRL activated Nrf2, as represented by an increase in nuclear Nrf2 and induction of Nrf2-dependent luciferase and, subsequently, HO-1, a target gene product of Nrf2. TRL activation of Nrf2 and induction of HO-1 were completely prevented by chemical reduction of the electrophilic functional group (α, β-unsaturated carbonyl group) in the drug. In parallel, TRL was reactive with the nucleophilic thiol group in N-acetylcysteine, forming a covalent adduct. Moreover, TRL, but not reduced TRL, binds to Kelch-like ECH-associated protein 1 (KEAP1), releasing Nrf2. TRL administration ameliorated colonic damage and inflammation in rats with dinitrobenzene sulfonic acid-induced colitis, which was partly compromised by the chemical reduction of TRL or co-treatment with an HO-1 inhibitor. Our results suggest that TRL activated the Nrf2-HO-1 pathway via covalent binding to KEAP1, partly contributing to TRL amelioration in rat colitis.

Identification of Potential Drug Targets of Broad-Spectrum Inhibitors with a Michael Acceptor Moiety Using Shotgun Proteomics.

The Michael addition reaction is a spontaneous and quick chemical reaction that is widely applied in various fields. This reaction is performed by conjugating an addition of nucleophiles with α, β-unsaturated carbonyl compounds, resulting in the bond formation of C-N, C-S, C-O, and so on. In the development of molecular materials, the Michael addition is not only used to synthesize chemical compounds but is also involved in the mechanism of drug action. Several covalent drugs that bond via Michael addition are regarded as anticarcinogens and anti-inflammatory drugs. Although drug development is mainly focused on pharmaceutical drug discovery, target-based discovery can provide a different perspective for drug usage. However, considerable time and labor are required to define a molecular target through molecular biological experiments. In this review, we systematically examine the chemical structures of current FDA-approved antiviral drugs for potential Michael addition moieties with α, β-unsaturated carbonyl groups, which may exert an unidentified broad-spectrum inhibitory mechanism to target viral or host factors. We thus propose that profiling the targets of antiviral agents, such as Michael addition products, can be achieved by employing a high-throughput LC-MS approach to comprehensively analyze the interaction between drugs and targets, and the subsequent drug responses in the cellular environment to facilitate drug repurposing and/or identify potential adverse effects, with a particular emphasis on the pros and cons of this shotgun proteomic approach.

A bis-pyrene chalcone based fluorescent material for ratiometric sensing of hydrazine: An acid/base molecular switch and solid-state emitter

In this work, we have designed and synthesized a new fluorescent molecular probe, DPY comprising of pyrene-diacetylpyridine conjugate, which was found to be sensitive to hydrazine as well as protonation. DPY is characterised by a strong emission both in solution (λem = 530 nm) as well as in solid state (λem = 610 nm), attributed to intramolecular charge-transfer. The probe responds to hydrazine with a ratiometric fluorescence emission change from yellow to blue, due to chalcone cyclisation reaction of α, β-unsaturated carbonyl group resulting in the pyrazoline compound, DPY-Hy, imparting a strong greenish-blue emission in solution. Further, the strong fluorescence emission of DPY in powder and thin film was quenched upon exposure to TFA, and revived upon exposure to TEA. For developing on-site detection protocol, when DPY was drop-casted on nonfluorescent silica plate a vivid naked-eye colour change from orange-red to dark blue was realized. Interestingly, in the aggregated state, DPY exhibited a broad range emission from green to orange in a mixed solvent system of THF:H2O. A plausible explanation of the photophysical events is substantiated with theoretical calculations.

Recent Development on Plant Aldehyde Dehydrogenase Enzymes and Their Functions in Plant Development and Stress Signaling.

Abiotic and biotic stresses induce the formation of reactive oxygen species (ROS), which subsequently causes the excessive accumulation of aldehydes in cells. Stress-derived aldehydes are commonly designated as reactive electrophile species (RES) as a result of the presence of an electrophilic α, β-unsaturated carbonyl group. Aldehyde dehydrogenases (ALDHs) are NAD(P)+-dependent enzymes that metabolize a wide range of endogenous and exogenous aliphatic and aromatic aldehyde molecules by oxidizing them to their corresponding carboxylic acids. The ALDH enzymes are found in nearly all organisms, and plants contain fourteen ALDH protein families. In this review, we performed a critical analysis of the research reports over the last decade on plant ALDHs. Newly discovered roles for these enzymes in metabolism, signaling and development have been highlighted and discussed. We concluded with suggestions for future investigations to exploit the potential of these enzymes in biotechnology and to improve our current knowledge about these enzymes in gene signaling and plant development.

Synthesis of β-Fluoro-α,β-Unsaturated Amides from the Fragmentation of Morpholine 3,3,3-Trifluoropropanamide by Grignard Reagents.

Fluoroalkenes serve as bioisosteres to peptide bonds and are resistant to hydrolytic enzymes in vivo. Currently, α-fluoro-α,β-unsaturated carbonyl compounds are readily accessible via general synthetic methods; however, β-fluoro-α,β-unsaturated carbonyl groups are more challenging to construct. To address this need, we have designed a reagent, morpholine 3,3,3-trifluoropropanamide, that creates (E)-β-fluoro-α,β-unsaturated amides upon the addition of many commonly used Grignard reagents. Reactions with this reagent enable a high level of stereocontrol in the fluoroalkene product.

Discovery of a new tetramethylpyrazine based chalcone with α, β-Unsaturated ketone moiety as a potential anticancer agent

In this study, a new ligustrazine-based chalcone molecule has been synthesized that contains an extra α, β-Unsaturated ketone moiety along with α, the β-Unsaturated carbonyl group of chalone. A new tetramethylpyrazine (TMP) based aldehyde was synthesized to make the TMP (ligustrazine) as part of chalcone and then it was reacted with newly synthesized ketone containing additional α, β-Unsaturated ketone moiety. After characterization, this new compound was evaluated for its effect on different types of cancer cell lines and very promising results were obtained. The growth of these cancer cells was inhibited by newly designed and synthesized compounds, especially for colon and pancreatic cancer cells with IC50 0.04 - 0.05 µM

Characterization of stable and reactive metabolites of piperine formed on incubation with human liver microsomes.

Black pepper, though commonly employed as a spice, has many medicinal properties. It consists of volatile oils, alkaloids, pungent resins, etc., of which piperine is a major constituent. Though safe at low doses, piperine causes alteration in the activity of drug metabolising enzymes and transporters at high dose and is known to precipitate liver toxicity. It has a potential to form reactive metabolite(s) (RM) owing to the presence of structural alerts, such as methylenedioxyphenyl (MDP), α, β-unsaturated carbonyl group (Michael acceptor), and piperidine. The present study was designed to detect and characterize stable and RM(s) of piperine formed on in vitro incubation with human liver microsomes. The investigation of RMs was done with the aid of trapping agents, viz, glutathione (GSH) and N-acetylcysteine (NAC). The samples were analysed by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS) using Thermo Scientific Q Exactive Plus Orbitrap. Full scan MS followed by data-dependent MS2 (Full MS-ddMS2 ) mode was used to establish mass spectrometric fragmentation pathways of protonated piperine and its metabolites. In total, four stable metabolites and their isomers (M1a-c, M2a-b, M3a-c, and M4a-b) were detected. Their formation involved removal of carbon (3, M1a-c), hydroxylation (2, M2a-b), hydroxylation with hydrogenation (3, M3a-c), and dehydrogenation (2, M4a-b). Out of these metabolites, M1, M2, and M3 are reported earlier in the literature, but their isomers and two M4 variants are novel. In addition, six novel conjugates of RMs, including three GSH conjugates of m/z 579 and three NAC conjugates of m/z 435, were also observed.

Virtual screening-guided discovery of thioredoxin reductase inhibitors

The selenoprotein thioredoxin reductase (TXNRD) is a promising therapeutic target for cancer. To discover novel TXNRD inhibitors, a library of α, β-unsaturated carbonyl compounds were applied in structure-based virtual screening for the selection of hit compounds. Fifteen top-ranked compounds were further validated experimentally, exhibiting potent inhibition of TXNRD and remarkable cytotoxicity to cancer cells. The further binding mode analysis indicated that multiple noncovalent interactions between the inhibitors and the active pocket of TXNRD facilitated the formation of covalent bonds between the Sec498 on TXNRD and the α, β-unsaturated carbonyl groups on inhibitors. Results from both simulations and experiments demonstrated that Sec498 is the prime interaction site for the inhibition of TXNRD. Taking compound 7 as an example, the inhibition of TXNRD by compounds promoted oxidative stress-mediated apoptosis of cancer cells. Given these findings, novel TXNRD inhibitors may be discovered and introduced to the growing fields of small molecule drugs against TXNRD.

Shogaol but not gingerol has a neuroprotective effect on hemorrhagic brain injury: Contribution of the α, β-unsaturated carbonyl to heme oxygenase-1 expression

We investigated the effects of shogaol, which has an α, β-unsaturated carbonyl group, and gingerol, which does not, on primary-cultured microglia to understand how the α, β-unsaturated carbonyl interacts with Kelch-like ECH-associated protein (Keap)1. Shogaol (1 μM) but not the same concentration of gingerol significantly increased heme oxygenase (HO)-1 protein levels in cultured microglia without cytotoxicity. In addition, shogaol suppressed the release of the inflammation marker nitric oxide induced by 30 U/ml thrombin treatment. A docking simulation suggested that the α, β-unsaturated carbonyl of shogaol but not gingerol interacts with Keap1. Nuclear import of nuclear factor E2-related factor 2 and increased binding of the HO-1 E2 enhancer support the docking-simulation prediction. The transcription inhibitor actinomycin D (0.1 μg/ml) markedly blocked the increase of HO-1 mRNA levels by shogaol. To evaluate whether the α, β-unsaturated carbonyl can be used for intracerebral hemorrhage (ICH) therapy, we investigated the effect of shogaol on an in vivo mouse ICH model. Intracerebroventricular injection of 0.2 nmol shogaol increased striatal HO-1 protein levels and rescued ICH-induced neuron loss. Thus, the α, β-unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression.

Accumulation of 9- and 13-KODEs in response to jasmonic acid treatment and pathogenic infection in rice.

The inducible metabolites in rice leaves treated with 1 mM jasmonic acid (JA) were analyzed using HPLC. We detected an increase in the levels of two compounds, 1 and 2. Based on the comparison with mass spectra and chromatographic behavior with authentic compounds, 1 and 2 were identified as 13-oxooctadeca-9,11-dienoic acid (13-KODE) and 9-oxooctadeca-10,12-dienoic acid (9-KODE), respectively, which have not been detected in rice to date. The accumulation of these compounds was also induced by an infection by Bipolaris oryzae. Treatment of rice leaves with KODEs induced the accumulation of defensive secondary metabolites, sakuranetin, naringenin, and serotonin, suggesting that KODEs may play a role in the elicitation of defense responses. The compounds that have an α, β-unsaturated carbonyl group similar to KODEs did not reproduce the response of accumulation of defensive secondary metabolites, suggesting that additional structural factors such as long hydrophobic carbon chain are needed to elicit defense responses.

Encouraging Effects of Ethacrynic Acid Derivatives Possessing a Privileged α, β-Unsaturated Carbonyl Structure Scaffold

α, β-unsaturated carbonyl unit has remarkable utility in the development of biologically active and therapeutically relevant compounds in medicinal chemistry. In recent years, a number of Ethacrynic acid (EA) derivatives containing α, β-unsaturated carbonyl group were reported, which displayed versatile biological activities, such as antitumor activity, antimalarial effects, antiviral activity and reducing intraocular pressure. In this review, we summed up a number of derivatives regarding Ethacrynic acid as the lead and α, β-unsaturated carbonyl moiety as the functional group, researching on structure-activity relationship and evaluating their various biological activities in recent years. By summarizing the structure-activity relationships of these derivatives, we aimed to demonstrate α, β-unsaturated carbonyl group is a privileged scaffold in these structures and we should pay more attention to α, β-unsaturated carbonyl group to the development of more effectively bioactive new compounds.'

Preparation, characterization, and in vitro drug release behavior of glutathione-sensitive long-circulation micelles based on polyethylene glycol prodrug

In this paper, a kind of glutathione-sensitive polymeric micelles was prepared through assembling in aqueous solution of an amphiphilic polymeric prodrug which was synthesized by linkage of 6-mercaptopurine (6-MP) and polyethylene glycol monomethyl ether using propiolic acid as a connecting arm. The glutathione (GSH)-sensitive strategy is based on a Michael addition–elimination reaction, that is the amphiphilic polymeric prodrug which contains α, β-unsaturated carbonyl group acts as a Michael acceptor to receive the attack of nucleophile – glutathione, and undergoes elimination reaction to release the original drug. Transmission electron microscope observation showed that the polymeric micelles (PMs) had a spherical-like morphology with a mean diameter of 28 ± 3.2 nm. The dynamic light scattering investigation data exhibited that the size and distribution changes of PMs are negligible after being placed for 15 days. In vitro drug release study indicated that only less than 13% of 6-MP was released from the micelles under GSH stimulation at micromolar level, while 34.5, 53.7, and 77.8% accumulative release rates were achieved under GSH stimulation at millimolar level (1, 2 and 10 mM), respectively. The cell inhibition rate of PM solution against HL-60 cells carried out by MTT method reached 85%. The cellular uptake and the intracellular drug release of PMs in HL-60 cells were observed through determining the intracellular 6-MP content by UV–vis spectrophotometer. In vitro macrophage uptake study showed a low phagocytosis rate, indicating the long-circulation ability of the PMs.