Cherng-Chyi Tzeng

Tajen University, P’ing-tung-chieh, Taiwan, Taiwan

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Publications (98)211.29 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of 2-furanylvinylquinoline derivatives were synthesized and evaluated for antiproliferative activities against the growth of four cancer cell lines including non-small cell lung cancer (A549 and H1299), breast cancer (MCF-7 and MDA-MB-231) and normal diploid embryonic lung cell line (MRC-5). Among them, (E)-6-methoxy-3-(4-methoxyphenyl)-2-[2-(5-nitrofuran-2-yl)vinyl]quinoline (10c) was found low cytotoxic in all cancer cells and normal cell. The aim of this study was to investigate the anti-invasive and anti-metastatic activity of compound 10c in H1299 human lung cancer cells. In this study, compound 10c inhibited the migration and invasion of cells in a concentration-dependent manner by wound healing assay and transwell invasion assay. Furthermore, the inhibition of both phosphorylation of Akt and ERK by compound 10c may be critical for cell migration and this may result in the down-regulation of several factors associated with cellular migration, including β-catenin transcription factor, Bcl-2 and COX-2. Interestingly, the treatment of compound 10c did not affect the expression level but reduced the activities of the MMP-2 and -9. The phosphorylation level of stress-activated kinase p38 was significantly increased following compound 10c treatment. To sum up, compound 10c had potential to suppress the migration and invasion of H1299 cancer cells in vitro and it could serve as a promising drug for the treatment of cancer metastasis.
    Bioorganic & Medicinal Chemistry. 11/2014;
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    ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third most common cause of cancer-related deaths. The objective of our research was to develop effective agents against HCC. Here, we have synthesized a series of anilinoquinoline derivatives. Based on a MTT assay and qRT-PCR in human Huh-7 hepatoma cells, we observed that 2-(2,6-dimethylanilino)quinoline (9) and 2-(3-benzenecarbonylanilino)quinoline (23) exhibited good antitumor activity. Besides, the polo-like kinase 1 (PLK1) positively correlated with aggressiveness of tumors and polo-like kinase 3 (PLK3) regarded as a tumor suppressor gene are serine/threonine kinases that play an essential role in carcinogenesis. Our results indicated that 2-anilinoquinoline (6) and 2-(3,5-dimethoxyanilino)quinoline (16) may decrease the expression levels of PLK1 gene, as well as increase the expression levels of PLK3 gene. We suggested this series of synthesized anilinoquinolines be promising to develop as novel regulating PLK molecular. Further, structural modification and the molecular mechanism of these compounds as a candidate are underway.
    Medicinal Chemistry Research 03/2014; 23(3). · 1.61 Impact Factor
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    ABSTRACT: Certain amide-containing anthraquinone, xanthone, and carbazole derivatives have been synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal carcinoma (NPC-TW01), lung carcinoma (NCI-H661), and leukemia (Jurkat). Among them, 2-(9,10-dioxo-9,10-dihydroanthracen-2-yloxy)-N-(naphthalen-2-yl)acetamide (13) was the most active against NPC-TW01 with an IC50 value of 2.62 µM while its xanthone and dibenzofuran counterparts, 14 and 15, were inactive with an IC50 value of 16.10 and 11.09 µM, respectively. Studies on NPC-TW01 cell cycle distribution revealed that compound 13 inhibited proliferation of NPC-TW01 by the alteration of cell division and the accumulation of cells in G0/G1 phase.
    Chemical & pharmaceutical bulletin 01/2014; 62(1):106-11. · 1.70 Impact Factor
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    ABSTRACT: [Formula: see text]-6-Hydroxy-9-methoxy-6-(piperazin-1-yl)-11[Formula: see text]-indeno[1,2-[Formula: see text]]quinolin-11-one [Formula: see text]-2-(pyrrolidin-1-yl)ethyl oxime (2c) was identified as a potential dual topo I/II inhibitor in our previous paper. In continuation for the search of more potent compounds, we describe herein the preparation of certain indeno[1,2-[Formula: see text]]quinoline derivatives and evaluation of their antiproliferation, DNA binding affinity, and topoisomerases (topo I and topo II) inhibitory activities. Among them, [Formula: see text]-9-[3-(dimethylamino)propoxy]-11[Formula: see text]-indeno[1,2-[Formula: see text]]quinolin-11-one [Formula: see text]-3-(dimethylamino)propyl oxime (11b) and its analog 11c exhibited approximately equal activity to the lead compound 2c against the growth of HeLa and A549 cancer cells. Both compounds 11b and 11c were more active than 2c in the inhibition of topo I and topo II. However, none of them exhibited significant DNA binding affinity while 2c was a very strong DNA binding agent. Compound 11b exhibited a high oral bioavailability of 39.8 % while the oral bioavailability of 2c and 11c was only 10.9 and 8.6 %, respectively. The in vivo anti-tumor evaluation of 11b in nude mice bearing subcutaneous breast cancer tumors revealed that treatment with low (10 mg/kg) or high (30 mg/kg) doses of 11b dramatically diminished tumor growth. Therefore, compound 11b is identified as a potential non-DNA intercalating dual topo I/II inhibitor.
    Molecular Diversity 09/2013; · 2.86 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection is a worldwide health problem. This can be attributed, in part, to the high mutation rate associated with RNA viral replication, which favors the emergence of drug resistance and limits the efficacy of current therapies. Here we report the continuation of our efforts to rationally design and synthesize a series of novel anilinobenzothiazole derivatives. We demonstrate that 2-(4-nitroanilino)-6-methylenzothiazole (compound 14) inhibited HCV RNA-dependent RNA polymerase (RdRp) activity and HCV RNA replication (EC50 = 8 ± 0.5 μM) in a dose-dependent manner, consistent with a noncompetitive model of inhibition (kinetic constant Ki = 7.76 μM). The best docking pose of compound 14 is located in the Thumb II Pocket, suggesting an inhibitory mechanism involving the docking of compound 14 that alters RdRp breathing. Combinations of compound 14 with interferon-α or other drugs potentially targeting HCV proteins, including telaprevir, PSI7977, or BMS790052, synergistically decreased the levels of HCV RNA.
    Antiviral research 08/2013; · 3.61 Impact Factor
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    ABSTRACT: Camptothecin (CPT) and its derivatives are powerful anticancer agents, but these compounds are chemically unstable due to their α-hydroxy lactone six-membered E-ring structure, which is essential for trapping topoisomerase I (topo I)-DNA cleavage complexes. Moreover, the reversibility of trapping the topo I-DNA cleavage complex and the tight binding of CPTs to human serum albumin limit the levels of available active drug. CPT analogs are the only clinically available drugs that target topo I. Owing to the clinical importance of CPT analogs, the development of new anticancer agents which inhibit topo I is urgently needed. In the present study, we report the synthesis, biologic evaluation, and molecular mechanism of a series of substituted indeno[1,2-c]quinoline derivatives against the growth of several human cancer cell lines. We found that 9-methoxy-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinoline-11-one O-3-(dimethylamino)propyl oxime (TCH-1030) intercalated into DNA and preferentially inhibited DNA topo I relaxation. Flow cytometric analysis and BrdU incorporation assays indicate that TCH-1030 alters cell cycle progression, induces S-phase arrest, and causes DNA polyploidy (>4 N) that is distinct from the typical G2-M arrest reported with known topoisomerase toxins. Our data indicate that TCH-1030 induces caspase 3 activation, PARP cleavage, γ-H2AX phosphorylation, and, consequently, DNA fragmentation and apoptosis. We also demonstrated that treatment with TCH-1030 significantly inhibits tumor growth in a BT483-xenograft nude mouse model. Taken together, we conclude that the primary mechanism of action of TCH-1030-induced cell cycle retardation and apoptosis-mediated DNA damage involves DNA binding and intercalation as well as topo I inhibition.
    Breast Cancer Research and Treatment 02/2013; · 4.47 Impact Factor
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    ABSTRACT: The hepatitis C virus (HCV) is the main cause of progressive liver disease, leading to the development of liver cirrhosis and hepatocellular carcinoma (HCC). Novel anilinocoumarins were synthesized, and their efficacy against HCV replication was evaluated. We demonstrated that 3-(3',4',5'-trimethoxyanilin-1'-yl)methylaminocoumarin () exhibited strong anti-HCV activity at protein and RNA levels at non-toxic concentrations, with an EC(50) value of 12 ± 0.3 μM and a selective index (SI) value of 10. Combined treatment of compound and interferon-α (IFN) or telaprevir induced a significant decrease in HCV RNA levels, respectively. We also found that the anti-HCV replication effect of compound was due to the induction of IFN-mediated antiviral responses. This is the first report demonstrating that coumarins inhibit viral replication through an IFN-mediated anti-viral response. Collectively, compound possessed potent activities against HCV replication and could be a new lead compound with higher selectivity and less toxicity.
    Organic & Biomolecular Chemistry 02/2013; · 3.57 Impact Factor
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    ABSTRACT: Certain 3-phenylquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) and (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (11) were identified as potential lead compounds for further development. Compound 6a was active against the growth of H1299 and SKBR-3 with IC(50) values of 1.41 and 0.70 μM respectively which was more active than the positive topotecan (IC(50) values of 6.02 and 8.91 μM respectively). Compound 11 exhibited an IC(50) value of less than 0.10 μM against the growth of MDA-MB231, and non-cytotoxic to the normal mammary epithelial cell (H184B5F5/M10). Mechanism studies indicated that compound 11 induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and consequently caused the cell death.
    European Journal of Medicinal Chemistry 11/2012; 59C:274-282. · 3.43 Impact Factor
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    ABSTRACT: β-Lapachone (β-LAPA), a natural product from the lapacho tree in South America, is a potential chemotherapeutic agent that exhibit a wide variety of pharmacological effects such as anti-virus, anti-parasitic, anti-cancer, and anti-inflammatory activities. In order to discover novel anti-inflammatory agents, we have synthesized a series of β-LAPA derivatives for evaluation. Among them, 4-(4-methoxyphenoxy)naphthalene-1,2-dione (6b) was found to be able to inhibit NO and TNF-α released in LPS-induced Raw 264.7 cells. Inhibition of iNOS and COX-2 was also observed in compound 6b treated cells. Mechanism studies indicated that 6b exhibited anti-inflammatory properties by suppressing the release of pro-inflammatory factors through down-regulating NF-κB activation. In addition, it suppressed NF-κB translocation by inhibiting the phosphorylation of p38 kinase. Our results also indicate that the inhibitory effect of 6b on LPS-stimulated inflammatory mediator production in Raw 264.7 cell is associated with the suppression of the NF-κB and MAPK signaling pathways. A low cytotoxicity (IC(50)=31.70μM) and the potent anti-inflammatory activity exhibited by compound 6b make this compound a potential lead for developing new anti-inflammatory agents. Further structural optimization of compound 6b is on-going.
    Bioorganic & medicinal chemistry 11/2012; · 2.82 Impact Factor
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    ABSTRACT: Certain 4,5-diarylisoxazole derivatives have been found to possess broad biological effects, including anti-inflammatory and anticancer activities. Recently, we have reported preparation of certain isoflavone derivatives and investigated for their anti-osteoporotic and antiproliferative activities in a detailed SAR study. The present report describes the conversion of isoflavones into novel 4,5-diphenylisoxazole derivatives by the treatment with NH2OH. Alkylation followed by amination of these 4,5-diphenylisoxazoles gave the desired aminoalkoxy substituted 4,5-diphenylisoxazole derivatives. These compounds were evaluated in vitro for the osteogenic differentiation and quantification of mineralization. Although 5-isopropoxy- 2-[4-(4-methoxyphenyl)isoxazol-5-yl]phenol (3) exhibited approximately 2.8-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (277% mineralization), the low cell viability (6%) and high cytotoxicity (68%) prompted us to further pursue more suitable candidates. A series of aminoalkyl side chains were introduced with aims to decreased cytotoxicity. Among them, 5-{4-isopropoxy-2-[4-(pyrrolidin-1-yl)butoxy]phenyl}-4-(4-methoxyphenyl)- isoxazole (7a) exhibited approximately 2-fold more activity than the positive Ipriflavone in the promotion of osteoblast activity (121% mineralization) with comparable cell viability (71% v.s. 77%). Compound 7a was non cytotoxic against hADSCs and therefore, was selected as a lead for further structural optimization.
    Medicinal chemistry (Shāriqah (United Arab Emirates)) 10/2012; · 1.64 Impact Factor
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    ABSTRACT: A number of 2,4,5-triaryl-1H-imidazole derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cell lines including three non-small cell lung cancers (H460, H1299, and A549), one breast cancer (MCF-7), and one normal diploid embryonic lung cell line (MRC-5). Preliminary results indicated that both 2-(5-bromofuran-2-yl)-4,5-bis{4-[3-(dimethylamino) propoxy] phenyl}-1H-imidazole (10f) and 4,5-bis{4-[3-(dimethylamino)propoxy]phenyl}-2-(5-nitrofuran-2-yl)-1H -imidazole (10g) were selectively active against the growth of H1229 with an IC(50) of less than 0.1 μM, thus were more active than topotecan (IC(50) > 10.0 μ M). However, both 10f and 10g exhibited only marginal cytotoxicity against H460, A549, MCF-7, and MRC-5 requiring an IC (50) of at least 4.16 μM. Our results also indicated that 10f induced H1299 cell cycle arrest at G0/G1 through the inactivation of p38 MAPK, JNK, ERK, as well as the expression of SIRT1 and survivin. These results suggested that 10f might have therapeutic potential against H1299 (non-small cell lung cancer cell).
    Molecular Diversity 09/2012; · 2.86 Impact Factor
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    ABSTRACT: We have synthesized certain 6-substituted 9-methoxy-11H-indeno[1,2-c]quinolin-11-ones for antiproliferative evaluation. Results indicated that 6-alkylamine derivatives, 6-[2-(dimethylamino)ethylamino]-9-methoxy-11H-indeno[1,2-c]quinolin-11-one (5a) and its 6-[3-(dimethylamino)propylamino] derivative, 5b, were able to inhibit cells growth completely at a concentration of 100 μM while most of the 6-arylamine derivatives 6b-6h were inactive at the same concentration. Comparable mean GI(50) (drug molar concentration causing 50% cell growth inhibition) values for 5a (3.47 μM) and 5b (3.39 μM) indicated the cytotoxicity may not be affected by the length of alkyl substituents at C-6 position. Compound 5b, with a mean GI(50) value of 3.39 μM, was the most active and therefore was selected for further evaluation on its effects of H460 lung cancer cell cycle distribution. Results indicated that 5b induced cell cycle arrest in G2/M phase after 24h treatment, while the hypodiploid (sub-G0/G1 phase) cells increased. We found that H460 cell became shrinked after the treatment of 5b, indicating that apoptosis may be a mechanism by which 5b kills the cancer cells. DNA unwinding assay indicated that 5b may bind to DNA through intercalation. Our results have also demonstrated that PARP was cleaved while caspase-3 and caspase-8 activities were induced after the treatment of 5b at 10 μM for 24h. Thus, compound 5b intercalates DNA, induces cell cycle arrest at G2/M phase via cleavage of PARP, induces caspase-3 and caspase-8 activities, and consequently causes the cell death.
    Bioorganic & medicinal chemistry 06/2012; 20(14):4397-404. · 2.82 Impact Factor
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    ABSTRACT: In fMLP (formyl-Met-Leu-Phe)-stimulated rat neutrophils, a mixture of regioisomers benzo[a]furo[2,3-c]phenazine-10-carboxylic acid and benzo[a]furo[2,3-c]phenazine-11-carboxylic acid (TCH-1116) inhibited O(2)(-) (superoxide anion) generation, which was not mediated by scavenging the generated O(2)(-) or by a cytotoxic effect on neutrophils. TCH-1116 had no effect on the arachidonic acid-induced NADPH oxidase activation in a cell-free system, whereas it effectively attenuated the phosphorylation of Ser residues in p47(phox) and the association between p47(phox) and p22(phox) in fMLP-stimulated neutrophils. The interaction of p47(phox) with PKC (protein kinase C) isoforms (α, βI, βII, δ and ζ) was attenuated by TCH-1116, whereas TCH-1116 did not affect the PKC isoforms membrane translocation, phosphorylation (Ser660) and kinase activity. TCH-1116 effectively attenuated the association between PKB/Akt (protein kinase B) and p47(phox), Akt phosphorylation (Thr308/Ser473) and kinase activities of Akt and human recombinant PDK (3-phosphoinositide-dependent kinase) 1, whereas it had no effect on recruitment of Akt, phospho-PDK1 (Ser241) and p110γ to membrane. Moreover, the interaction of p21-activated kinase (PAK) 1 with p47(phox) and the phosphorylation of PAK1 (Thr423 but not Ser144) were inhibited by TCH-1116, but without affecting the membrane recruitment of PAK1. The cellular cyclic AMP level was not changed by TCH-1116. Taken together, these results suggest that TCH-1116 inhibits fMLP-stimulated O(2)(-) generation in rat neutrophils through the blockade of PKC, Akt and PAK signaling pathways.
    European journal of pharmacology 05/2012; 682(1-3):171-80. · 2.59 Impact Factor
  • Current Nanoscience 04/2012; 8(2):266-273. · 1.36 Impact Factor
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    ABSTRACT: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenyl) amino]furo[2,3-b]quinoline (PK-L4) is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection. To utilize solid lipid nanoparticles (SLNs) modified with polyethylene glycol (PEG) to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration. The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE%) of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%-64% in the human lung carcinoma cell line (A549), 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7), and 95% in the human breast adenocarcinoma cell line (MDA-MB-231). The amount of PK-L4 released by SLNs with PEG was significantly higher than that from the PK-L4 solution (P < 0.05). After intravenous bolus of the PK-L4-loaded SLNs with PEG, there was a marked significant difference in half-life alpha (0.136 ± 0.046 hours) when compared with the PK-L4 solution (0.078 ± 0.023 hours); also the area under the curve from zero to infinity did not change in plasma when compared to the PK-L4 solution. This demonstrated that PK-L4-loaded SLNs were rapidly distributed from central areas to tissues and exhibited higher accumulation in specific organs. The highest deposition of PK-L4-loaded SLNs with PEG was found in the lung and spine. Sufficient amounts of PK-L4 were entrapped in the SLNs, and the pharmacokinetic behavior of PK-L4-loaded SLNs was established. This formulation successfully resolved the delivery problem, and the drug was localized in particular organs.
    International Journal of Nanomedicine 01/2012; 7:4995-5005. · 4.20 Impact Factor
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    ABSTRACT: This study describes the synthesis and anti-inflammatory effects of furo[3', 2':3,4]naphtho[1,2-d] imidazole derivatives. Among these furo[3', 2':3,4]naphtho[1,2-d]imidazole derivatives, 2-(4-methoxyphenyl)furo [3', 2':3,4]naphtho[1,2-d]imidazole (12) exhibited a strong inhibitory activity against LPS-induced PGE(2) production, with an IC(50) value of 47 nM. Compound 12 is then further examined for its inhibitory effects in the protein expression of COX-2 and microsomal prostaglandin E(2) synthase-1 (mPGES-1) in Raw 264.7 cells. Our results indicate that compound 12 was capable against inhibiting LPS-induced mPGES-1 protein expression at a concentration of 1.0 μM and no inhibitory effect in COX-2 expression. The sepsis-induced PGE(2) production in rat serum decreased ~250% by the pretreatment of 12 at 10 mg/kg. These results are especially important since compound 12 exhibited good oral bioavailability (72%) and was not cytotoxic at a concentration of 10.0 μM. Therefore, compound 12 is a highly selective mPGES-1 inhibitor that can serve as a lead for the development of novel oral anti-inflammatory drug candidates.
    Molecular Diversity 12/2011; 16(2):215-29. · 2.86 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. Here, we have synthesized a series of anilinoquinoline derivatives. Based on a cell-based HCV replicon system, we observed that 2-(3'-nitroanilino)quinoline (18) exhibited anti-HCV activity with a 50% effective concentration (EC(50)) value of 7μM and a selective index (SI) value of 10. In addition, compound 18 possessed the inhibitory effect on HCV NS3/4A protease activity. Therefore, we concluded that the compound 18 possessed a potent activity against HCV replication and could provide as a new lead compound as anti-HCV inhibitor.
    Bioorganic & medicinal chemistry letters 12/2011; 22(2):1107-10. · 2.65 Impact Factor
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    ABSTRACT: A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65μM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce apoptosis via activation of p53, Bax, and caspase-8 which consequently cause cell death.
    Bioorganic & medicinal chemistry 10/2011; 19(24):7653-63. · 2.82 Impact Factor
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    ABSTRACT: We have reported the preparation and anticancer evaluation of certain 4-anilinofuro[2,3-b]quinolines. However, drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by these compounds prompted us to search for newer derivatives. Among them, (E)-1-(4-(furo[2,3-b]quinolin-4-ylamino)phenyl)ethanone O-2-aminoethyloxime (13a) is selectively active against the growth of NCI-H460 and is highly water-soluble (63 μg/mL). Its hydrochloride salt, 13a·HCl exhibited not only excellent water solubility (1049 μg/mL) but also a high oral bioavailability (57.1%). Compound 13a may cause cancer cell apoptosis through inducing mitotic arrest and mitotic catastrophe mechanism. Xenographic studies indicated the tumor size with 13a·HCl treated nude mice was significantly lower than control. Further evaluation in an orthotopic lung cancer model indicated that 13a·HCl can be absorbed readily through oral administration, distributed to lung tissue, and exhibited significant efficacy in inhibiting the growth of lung cancers.
    Journal of Medicinal Chemistry 06/2011; 54(13):4446-61. · 5.61 Impact Factor
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    ABSTRACT: Certain indeno[1,2-c]quinolines were synthesized and evaluated for antiosteoclastogenic activities. Among them, 6,9-dimethoxy-11H-indeno[1,2-c]quinolin-11-one (8a) and 9-methoxy-6-(methylthio)-11H-indeno[1,2-c]quinolin-11-one (16a) inhibited RANKL-induced osteoclast formation in Raw 264.7 cells with an IC(50) of 2.00 and 2.58 μM, respectively. Compound 8a was only weakly active in the inhibition of the RANKL-induced NFAT activation, while 16a was inactive. These results indicated that the antiosteoclastogenic effect of 8a is only partly related while 16a is not related to the suppression of NFAT.
    Journal of Medicinal Chemistry 04/2011; 54(8):3103-7. · 5.61 Impact Factor

Publication Stats

438 Citations
211.29 Total Impact Points


  • 2014
    • Tajen University
      P’ing-tung-chieh, Taiwan, Taiwan
  • 2000–2014
    • Kaohsiung Medical University
      • • Department of Pharmacy
      • • Department of Medicinal and Applied Chemistry
      • • College of Life Sciences
      Kao-hsiung-shih, Kaohsiung, Taiwan
  • 2012
    • Yuanpei University
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2007–2012
    • China Medical University Hospital
      • Department of Radiology
      臺中市, Taiwan, Taiwan
  • 2005–2009
    • University of Rhode Island
      Kingston, Rhode Island, United States
    • Chung Shan Medical University
      • Institute of Medicine
      Taichung, Taiwan, Taiwan
  • 2004–2009
    • National Taiwan University
      • College of Medicine
      Taipei, Taipei, Taiwan
  • 2006
    • Taichung Veterans General Hospital
      • Department of Internal Medicine
      臺中市, Taiwan, Taiwan