Design and synthesis of novel imidazole-chalcone derivatives as microtubule protein polymerization inhibitors to treat cervical cancer and reverse cisplatin resistance.

Using the licochalcone moiety as a lead compound scaffold, 16 novel imidazole-chalcone derivatives were designed and synthesized as microtubule protein polymerization inhibitors. The proliferation inhibitory activities of the derivatives against SiHa (human cervical squamous cell carcinoma), C-33A (human cervical cancer), HeLa (human cervical cancer), HeLa/DDP (cisplatin-resistant human cervical cancer), and H8 (human cervical epithelial immortalized) cells were evaluated. Compound 5a exhibited significant anticancer activity with IC50 values ranging from 2.28 to 7.77 µM and a resistance index (RI) of 1.63, while showing minimal toxicity to normal H8 cells. When compound 5a was coadministered with cisplatin, the RI of cisplatin to HeLa/DDP cells decreased from 6.04 to 2.01, while compound 5a enhanced the fluorescence intensity of rhodamine 123 in HeLa/DDP cells. Further studies demonstrated that compound 5a arrested cells at the G2/M phase, induced apoptosis, reduced colony formation, inhibited cell migration, and inhibited cell invasion. Preliminary mechanistic studies revealed that compound 5a decreased the immunofluorescence intensity of α-/ß-tubulin in cancer cells, reduced the expression of polymerized α-/ß-tubulin, and increased the expression of depolymerized α-/ß-tubulin. Additionally, the molecular docking results demonstrate that compound 5a can interact with the tubulin colchicine binding site and generate multiple types of interactions. These results suggested that compound 5a has anticancer effects and significantly reverses cervical cancer resistance to cisplatin, which may be related to its inhibition of microtubule and P-glycoprotein (P-gp) activity.

Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3-Triazoles: A Computational Docking Techniques.

A very interesting foundation for this study is the creation of new methods for modifying compounds with a 1,2,3-triazole and chalcone scaffolds, as these compounds are significant in organic synthesis, particularly in the synthesis of bioactive organic compounds. To contribute to the development of an efficient method for the conversion of antimicrobial and antituberculosis heterocyclics, a novel series of cyclohepta pyridinone fused 1,2,3-triazolyl chalcones were designed and synthesized. All the newly prepared scaffolds were characterized by FT-IR, NMR (1H & 13C) and mass spectrometry. Among the tested compounds, hybrids 8b, 8d, and 8f exhibited exceptional antibacterial susceptibilities with zone of inhibition 27.84±0.04, 32.27±0.02, and 38.26±0.01 mm against the tested E. faecalis bacteria, whereas 8d had better antitubercular potency against M. tuberculosis H37Rv strain with MIC value 5.25 µg/mL, compared to Streptomycin [MIC=5.01 µg/mL]. All the synthesized compounds were initially assessed in silico against the targeted protein i. e., DprE1 that indicated compound 8d, 8f and 8h along with several other 1,2,3-triazole compounds as possible inhibitors. Based on docking results, 8d showed that the amino acids His74(A), Lys76(A), Cys332(A), Asp331(A), Val307(A), Tyr357(A), Met226(A), Gln276(A), Gly75(A), Peo58(A), Leu259(A), and Lys309(A) exhibited highly stable binding to DprE1 receptor of Mycobacterium tuberculosis (PDB: 4G3 U). Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion).

Quinazoline-chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in-silico studies of potential anticancer activity against multiple myeloma.

Two new series of quinazoline-chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5-trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy-substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)-8226 cells by 96%, at 10 µM with IC50 = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC50 = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl-2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI-8226 cells showed that the trimethoxy-substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc-containing binding site of HDAC6 and HDAC8.

Synthesis, Antimicrobial Activities, and Molecular Modeling Studies of Agents for the Sortase A Enzyme.

Sortase A (SrtA) is an attractive target for developing new anti-infective drugs that aim to interfere with essential virulence mechanisms, such as adhesion to host cells and biofilm formation. Herein, twenty hydroxy, nitro, bromo, fluoro, and methoxy substituted chalcone compounds were synthesized, antimicrobial activities and molecular modeling strategies against the SrtA enzyme were investigated. The most active compounds were found to be T2, T4, and T19 against Streptococcus mutans (S. mutans) with MIC values of 1.93, 3.8, 3.94 µg/mL, and docking scores of -6.46, -6.63, -6.73 kcal/mol, respectively. Also, these three active compounds showed better activity than the chlorohexidine (CHX) (MIC value: 4.88 µg/mL, docking score: -6.29 kcal/mol) in both in vitro and in silico. Structural stability and binding free energy analysis of S.mutans SrtA with active compounds were measured by molecular dynamic (MD) simulations throughout 100 nanoseconds (ns) time. It was observed that the stability of the critical interactions between these compounds and the target enzyme was preserved. To prove further, in vivo biological evaluation studies could be conducted for the most promising precursor compounds T2, T4, and T19, and it might open new avenues to the discovery of more potent SrtA inhibitors.

Chalcone-inspired rA1 /A2A adenosine receptor ligands: Ring closure as an alternative to a reactive substructure.

Over the past few years, great progress has been made in the development of high-affinity adenosine A1 and/or A2A receptor antagonists-promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure-related concerns. The present study investigated the effect of ring closures on the rA1 /A2A affinity of compounds containing a highly reactive α,ß-unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico and in vitro. The test compounds performed well upon qualitative assessment of drug-likeness and were generally found to be free from potentially problematic fragments. Most also showed low/weak cytotoxicity. Results from radioligand binding experiments confirm that heterocycles (particularly 2-substituted 3-cyanopyridines) can replace the promiscuous α,ß-unsaturated ketone functional group without compromising A1 /A2A affinity. Structure-activity relationships highlighted the importance of hydrogen bonds in binding to the receptors of interest. Compounds 3c (rA1 Ki  = 16 nM; rA2A Ki  = 65 nM) and 8a (rA1 Ki  = 102 nM; rA2A Ki  = 37 nM), which both act as A1 antagonists, showed significant dual A1 /A2A affinity and may, therefore, inspire further investigation into heterocycles as potentially safe and potent adenosine receptor antagonists.

Design and synthesis of naphthylchalcones as novel anti-leukaemia agents.

A series of new hydroxylated chalcone derivatives with different substitution patterns on a phenyl ring A and B, were prepared by Claisen-Schmidt condensation in an aqueous alkaline base. The antiproliferative activity of the studied compounds was evaluated against the human leukaemia cell line U-937. The structure-activity relationship of these naphthylchalcones was investigated by the introduction of one methoxy or two methyl groups on the A ring, the introduction of a methoxy group on the naphthyl ring or by varying the position of the methoxy group on the A ring. The results revealed that the naphthylchalcone containing a methoxy group in position 6́ of the A ring was the most cytotoxic compound, with an IC50 value of 4.7 ± 0.5 µM against U-937 cells. This synthetic chalcone induced S and G2-M cell cycle arrest, a time-dependent increase in sub-G1 ratio and annexin-V positive cells, caspase activation and poly(ADP-ribose) polymerase cleavage. Apoptosis induction was blocked by a pan-caspase inhibitor and by the selective caspase-3/7 inhibitor and attenuated by the inhibition of c-jun N-terminal kinases / stress-activated protein kinases (JNK/SAPK) and phosphoinositide 3-kinase. The structure-activity relationship of naphthylchalcones against human leukaemia cells reveals that the major determining in cytotoxicity is the presence of a methoxy group in position 6́ of the A ring that suggest the potential of this compound or derivatives in the development of new anti-leukaemia drugs.

Multi-step Synthesis, Characterization and Photophysical Investigation of Novel Biologically Active Heterocyclic Chalcone (AECO).

Novel alkylated heterocyclic chalcone (E)-1-(2-(allyloxy)phenyl)-3-(9-ethyl-9H-carbazol-3-yl)prop-2-en-1-one (AECO) with extended π-bond was prepared by the multi-steps synthesis. The structure of the AECO was established by the spectroscopic technics and purity of the compound was confirmed by the elemental analysis. Physicochemical parameters of the AECO such as molar absorption coefficient, transition dipole moments, stokes shift, oscillator strength and fluorescence quantum yield were calculated in ten various solvents on the basis of polarity of the solvents to see the effect of the solvent with AECO. Interaction of the AECO chromophore with cationic CTAB and anionic SDS surfactants were determined by using the fluorescence spectroscopy techniques. The intensity of the florescence spectrum increase with increasing the concentrations of surfactants. This suggests that strong interaction occurs between AECO with surfactants and this interaction arise from electrostatic forces. So, AECO chromophore could be used as analysis to define the Critical Micelle Concentration (CMC) of the surfactants. In addition the in-vitro antibacterial active of novel heterocyclic chalcone agents four bacteria's strain were evaluated and result showed AECO is beater antibacterial agent against Gram-Negative Bacteria (E. coli and S. flexneri) as compare to the Gram Negative Bacteria with respected to the standard drug Tetracycline.

Photophysical Study and Biological Applications of Synthetic Chalcone-Based Fluorescent Dyes.

A chalcone series (3a-f) with electron push-pull effect was synthesized via a one-pot Claisen-Schmidt reaction with a simple purification step. The compounds exhibited strong emission, peaking around 512-567 nm with mega-stokes shift (∆λ = 93-139 nm) in polar solvents (DMSO, MeOH, and PBS) and showed good photo-stability. Therefore, 3a-f were applied in cellular imaging. After 3 h of incubation, green fluorescence was clearly brighter in cancer cells (HepG2) compared to normal cells (HEK-293), suggesting preferential accumulation in cancer cells. Moreover, all compounds exhibited higher cytotoxicity within 24 h toward cancer cells (IC50 values ranging from 45 to 100 µM) than normal cells (IC50 value >100 µM). Furthermore, the antimicrobial properties of chalcones 3a-f were investigated. Interestingly, 3a-f exhibited antibacterial activities against Escherichia coli and Staphylococcus aureus, with minimum bactericidal concentrations (MBC) of 0.10-0.60 mg/mL (375-1000 µM), suggesting their potential antibacterial activity against both Gram-negative and Gram-positive bacteria. Thus, this series of chalcone-derived fluorescent dyes with facile synthesis shows great potential for the development of antibiotics and cancer cell staining agents.

Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction.

Two series of chalcone/aryl carboximidamide hybrids 4a-f and 6a-f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.

Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of Acinetobacter baumannii by Inhibiting ompA Gene Expression.

An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2'-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.

Design, synthesis and biological evaluation of novel chalcone-like compounds as potent and reversible pancreatic lipase inhibitors.

Pancreatic lipase (PL), a crucial enzyme responsible for hydrolysis of dietary lipids, has been validated as a key therapeutic target to prevent and treat obesity-associated metabolic disorders. Herein, we report the design, synthesis and biological evaluation of a series of chalcone-like compounds as potent and reversible PL inhibitors. Following two rounds of structural modifications at both A and B rings of a chalcone-like skeleton, structure-PL inhibition relationships of the chalcone-like compounds were studied, while the key substituents that would be beneficial for PL inhibition were revealed. Among all tested chalcone-like compounds, compound B13 (a novel chalcone-like compound bearing two long carbon chains) displayed the most potent PL inhibition activity, with an IC50 value of 0.33 µM. Inhibition kinetic analyses demonstrated that B13 could potently inhibit PL-mediated 4-MUO hydrolysis in a mixed inhibition manner, with the Ki value of 0.12 µM. Molecular docking simulations suggested that B13 could tightly bind on PL at both the catalytic site and a non-catalytic site that was located on the surface of PL, which was consistent with the mixed inhibition mode of this agent. In addition, B13 displayed excellent stability in artificial gastrointestinal fluids and good metabolic stability in human liver preparations. Collectively, our findings suggested that chalcone-like compounds were good choices for design and development of orally administrated PL inhibitors, while B13 could be served as a promising lead compound to develop novel anti-obesity agents via targeting on PL.

Synthesis and Biological Evaluation of Amino Chalcone Derivatives as Antiproliferative Agents.

Chalcone is a common scaffold found in many biologically active compounds. The chalcone scaffold was also frequently utilized to design novel anticancer agents with potent biological efficacy. Aiming to continue the research of effective chalcone derivatives to treat cancers with potent anticancer activity, fourteen amino chalcone derivatives were designed and synthesized. The antiproliferative activity of amino chalcone derivatives was studied in vitro and 5-Fu as a control group. Some of the compounds showed moderate to good activity against three human cancer cells (MGC-803, HCT-116 and MCF-7 cells) and compound 13e displayed the best antiproliferative activity against MGC-803 cells, HCT-116 cells and MCF-7 cells with IC50 values of 1.52 µM (MGC-803), 1.83 µM (HCT-116) and 2.54 µM (MCF-7), respectively which was more potent than the positive control (5-Fu). Further mechanism studies were explored. The results of cell colony formatting assay suggested compound 10e inhibited the colony formation of MGC-803 cells. DAPI fluorescent staining and flow cytometry assay showed compound 13e induced MGC-803 cells apoptosis. Western blotting experiment indicated compound 13e induced cell apoptosis via the extrinsic/intrinsic apoptosis pathway in MGC-803 cells. Therefore, compound 13e might be a valuable lead compound as antiproliferative agents and amino chalcone derivatives worth further effort to improve amino chalcone derivatives' potency.

Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors.

A library of new phenstatin based indole linked chalcone compounds (9a-z and 9aa-ad) were designed and synthesized. Of these, compound 9a with 1-methyl, 2- and 3-methoxy substituents in the aromatic ring was efficacious against the human oral cancer cell line SCC-29B, spheroids, and in a mouse xenograft model of oral cancer AW13516. Compound 9a exhibited anti-cancer activity through disrupting cellular integrity and affecting glucose metabolism-which is a hallmark of cancer. The cellular architecture was affected by inhibition of tubulin polymerization as observed by an immunofluorescence assay on 9a-treated SCC-29B cells. An in vitro tubulin polymerization kinetics assay provided evidence of direct interaction of 9a with tubulin. This physical interaction between tubulin and compound 9a was further confirmed by Surface Plasmon Resonance (SPR) analysis. Molecular docking experiments and validations revealed that compound 9a interacts and binds at the colchicine binding site of tubulin and at active sites of key enzymes in the glucose metabolism pathway. Based on in silico modeling, biophysical interactions, and pre-clinical observations, 9a consisting of phenstatin based indole-chalcone scaffolds, can be considered as an attractive tubulin polymerization inhibitor candidate for developing anti-cancer therapeutics.

Synthesis, spectral characterization and antimicrobial studies of novel series of allylidene based multifaceted chalcones analogues.

Following the Claisen Schmidt condensation a series of chalcone, their allylidene derivatives and metallic complexes were produced and subsequently screened for antibacterial assay. The precursors were simple acetophenone and different substituted aryl benzaldehydes; which were made to react in basic ethanolic conditions. The structure of synthesized targets was established by IR, 1H-NMR and EIMS data. The antibacterial statistics showed that most of the bacterial strains particularly S. typhi and E. coli were potently inhibited by majority of the compounds like 3c, 5c, 7a & 7c. This structure activity relationship studies showed that these molecules possessed p-methoxy substituents in their framework and found active in rupturing the cell wall. These molecules might serve as potential drug candidates for future drug discovery and design. The presented manuscript highlights the pharmacological diversity of chalcones holding allylidene moiety and Zn+2 complexes.

Synthesis and biological evaluation of chalcone derivatives as neuroprotective agents against glutamate-induced HT22 mouse hippocampal neuronal cell death.

Seventeen chalcone analogues were synthesized from 7-methoxy-3,4-dihydronaphthalen1(2H)-one and various aromatic aldehydes under basic conditions and their therapeutic properties were studied in mouse hippocampal cell line HT-22 against neuronal cell death induced by glutamate. From this study, we selected an analogue C01 as a active compound which showed significantly high neuroprotection. This compound inhibited Ca2+ influx and reactive oxygen species (ROS) accumulation inside cells. The glutamate-induced cell death was analyzed by flow cytometry and it showed that C01 significantly reduced apoptotic or dead cell induced by 5 mM glutamate. Western blot analysis indicates that glutamate-mediated activation of MAPKs were inhibited by compound C01 treatment. In addition, the C01enhanced Bcl-2 and decreased Bax, the anti and pro apoptotic proteins respectively. Further analysis showed that, C01 prevented the nuclear translocation of AIF (apoptosis inducing factor) and inhibited neuronal cell death. Taken together, compound C01 treatment resulted in decreased neurotoxicity induced by 5 mM of glutamate. Our finding confirmed that compound C01 has neuro-therapeutic potential against glutamate-mediated neurotoxicity.

Synthesis and evaluation of the anticancer activity of bischalcone analogs in human lung carcinoma (A549) cell line.

Bischalcone has gained much attention because of its wide range of application in pharmaceutical chemistry. This work aims to evaluate the antiproliferation effects and explore the anticancer mechanism of bischalcone analogs on human lung cancer A549 cells. In this study, we synthesized a series of bischalcone analogs via Aldol condensation reaction; MTT method was used to evaluate the antiproliferation effects; the 2',7'-dichlorofluorescein fluorescence assay was used to determine the intracellular reactive oxygen species levels; the glutathione reductase-DTNB recycling assay was used to detect the redox imbalance; determination of thiobarbituric acid-reactive substance was used to evaluate the lipid peroxidation; Rhodamine 123 was used to test the mitochondrial membrane potential (MMP); the FITC/PI kit was used to detect the apoptosis; Western blotting was used to detect the expression of Bax and Caspase 3. After treatment with curcumin and bischalcone analogs, compounds 1d and 1g, the more stabilities compounds than curcumin, exhibited much higher potency in A549 cells than curcumin and other bischalcone analogs. Further mechanism of action studies revealed that 1d and 1g exhibited more stronger reactive oxygen species production abilities than curcumin and accompanied by the redox imbalance, lipid peroxidation, the loss of MMP, the activition of Bax and Caspase 3, and ultimately resulted in apoptosis of A549 cell. These data suggest that enhancing the reactive oxygen species generation ability of bischalcone analogs may be a promising strategy for the treatment of human lung cancer.

Synthesis and anti-proliferative activity of a novel 1,2,3-triazole tethered chalcone acetamide derivatives.

A new series of 1,2,3-triazole tethered chalcone acetamide derivatives (7a-c &8a-r) have been synthesized in excellent yields and their structures were determined by analytical and spectral (FT-IR, 1H NMR, 13C NMR & HRMS) studies. The newly synthesized derivatives were evaluated for their cytotoxic activity against four human cancer cell lines, such as HeLa (Human cervical cancer), A549 (Human alveolar adenocarcinoma), MCF-7 (Human breast adenocarcinoma) and SKNSH (Human brain cancer). Among them, compound 7c exhibited good anti-proliferation activity with HeLa (IC50 7.41 + 0.8 µM), SKNSH (IC50 8.68 + 1.1 µM), MCF-7 (IC50 9.76 + 1.3 µM) and MDA-MB-231, while compounds 7a and 7b showed promising anti-proliferation against above four human cancer cell lines with IC50 7.95-11.62 µM, respectively, compared with the standard drug Doxorubicin. We explored the probable key active site and binding mode interactions in HDAC8 (PDB ID:3SFH) and EHMT2 (PDB ID:3K5K) proteins. The docking results are complementary to the experimental observations.

A chalcone derivative binds a putative allosteric site of YopH: Inhibition of a virulence factor of Yersinia.

Identification of allosteric inhibitors of PTPs has attracted great interest as a new strategy to overcome the challenge of discover potent and selective molecules for therapeutic intervention. YopH is a virulence factor of the genus Yersinia, validated as an antimicrobial target. The finding of a second substrate binding site in YopH has revealed a putative allosteric site that could be further exploited. Novel chalcone compounds that inhibit PTPs activity were designed and synthesized. Compound 3j was the most potent inhibitor, interestingly, with different mechanisms of inhibition for the panel of enzymes evaluated. Further, our results showed that compound 3j is an irreversible non-competitive inhibitor of YopH that binds to a site different than the catalytic site, but close to the well-known second binding site of YopH.

A novel highly selective fluorescent probe with new chalcone fluorophore for monitoring and imaging endogenous peroxynitrite in living cells and drug-damaged liver tissue.

As a member of the reactive nitrogen species (RNS) family, peroxynitrite (ONOO-) as an oxidant and nitrating mediator plays a significant role in some physiopathologic processes. The excessive production of peroxynitrite anion in a drug-damaged liver is a culprit of hepatotoxicity. The detection of peroxynitrite is of vital importance for the treatment of some diseases including cancer and liver injury. In this study, a novel turn-on fluorescent probe IC-ONOO with new chalcone fluorophore was designed and synthesized for the detection of in vitro and in vivo. The probe responded rapidly towards ONOO- (only within 15 min did the fluorescent intensity maximize), and was endowed with high sensitivity and excellent selectivity. Given the fact that the linear correlation between the fluorescent intensity at 560 nm and the concentrations of the probe ranged from 0 to 9 µM, the limit of detection (LOD) was calculated to be 3.1 × 10-8 M. With all the merits, probe IC-ONOO was qualified as a robust tool to monitor peroxynitrite anion under physiopathologic condition. Moreover, it was successfully applied in the imaging of endogenous peroxynitrite in living MCF-7 cells (Human breast carcinoma cells) and mouse drug-damaged liver tissue with low cytotoxicity. Given all the extraordinary merits, great potential has been seen in its application to other peroxynitrite related diseases.

Synthesis and anti-inflammatory evaluation of new chalcone derivatives bearing bispiperazine linker as IL-1ß inhibitors.

In this work, a series of novel chalcone derivatives bearing bispiperazine linker have been synthesized and in vitro anti-inflammatory, cytotoxic activity and anti-inflammatory mechanism have been screened. The results indicated that most bispiperazinochalcone derivatives displayed good inhibition of NO (IC50 < 20 µM) and low cytotoxicity (CC50 > 40 µM), and selectively inhibited the production of IL-1ß via inhibiting NLRP3 inflammasome activation, as promising candidate compounds for the treatment of NLRP3 inflammasome-driven diseases.