Browsing by Author "Hsu, Ming-Hua"

Now showing 1 - 8 of 8

Design and synthesis of pyridine-pyrazole-sulfonate derivatives as potential anti-HBV agents
(2016)
Chuang, Hong
;
Huang, Lin-Chiang Sherlock
;
Kapoor, Mohit
;
Liao, Yi-Jen
;
Yang, Cheng-Lin
Hepatitis B virus (HBV) is an infectious disease, which can cause acute and chronic infections. Every year, over 7.5 million persons die due to HBV. No effective drug exists for the treatment of HBV. Thus, we designed and synthesized 16 new pyridine-pyrazole-sulfonate compounds containing pyridine-SCH2-pyrazole and pyridine-pyrazole derivatives. Their structures were characterized by H-1-NMR, C-13-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the compounds were evaluated for their anti-HBV activities and a structure-activity relationship (SAR) in HepG2 2.2.15 cells was established. We found that the pyridine-pyrazole derivatives could inhibit the HBV gene expression and viral DNA replication. Among these compounds, 2-[3-(2-nitrophenylsulfonyl)oxy-5-pyrazol-yl]pyridine 19d has shown the most potent inhibitory activity with an IC50 value of 9.19 mu M and high selectivity index, SI (TC50/IC50) of 35.46. Hence, we believe our compounds could serve as a potential lead compounds for anti-HBV drug development.
Development of a Growth- Hormone- Conjugated Nanodiamond Complex for Cancer Therapy
(2014-05-01)
Chu, Hsueh-Liang
;
Chen, Hung-Wei
;
Tseng, Shin-Hua
;
Hsu, Ming-Hua
;
Ho, Li-Ping
It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a nanoblast and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.
Development of nordihydroguaiaretic acid derivatives as potential multidrug-resistant selective agents for cancer treatment
(2015-01-01)
Huang, Lin-Chiang Sherlock
;
Chuang, Hong
;
Kapoor, Mohit
;
Hsieh, Cheng-Ying
;
Chou, Shih-Ching
In this research, we designed and synthesized a new series of nordihydroguaiaretic acid (NDGA) derivatives for multidrug resistance (MDR) research. A methylsulfonyl NDGA derivative, ((2R,3S)-2,3-dimethylbutane-1,4-diyl)bis(benzene-4,1,2-triyl) tetramethanesulfonate (5d), was found to inhibit MDR1 gene expression and suppress drug resistantMES-SA/Dx5 cells. Moreover, the combination of 5d and doxorubicin/terameprocol (M4N) showed a profound synergistic effect on inhibition of drug resistant cancer cells, suggesting that 5d is a potential adjuvant applied with doxorubicin or terameprocol in cancer treatment.
Directly Thiolated Modification onto the Surface of Detonation Nanodiamonds
(2014-05-28)
Hsu, Ming-Hua
;
Chuang, Hong
;
Cheng, Fong-Yu
;
Huang, Ying-Pei
;
Han, Chien-Chung
An efficient method for modifying the surface of detonation nanodiamonds (5 and 100 nm) with thiol groups (-SH) by using an organic chemistry strategy is presented herein. Thiolated nanodiamonds were characterized by spectroscopic techniques, and the atomic percentage of sulfur was analyzed by elemental analysis and X-ray photoelectron spectroscopy. The conjugation between thiolated nanodiamonds and gold nanoparticles was elucidated by transmission electron microscopy and UV-vis spectrometry. Moreover, the material did not show significant cytotoxicity to the human lung carcinoma cell line and may prospectively be applied in bioconjugated technology. The new method that we elucidated may significantly improve the approach to surface modification of detonation nanodiamonds and build up a new platform for the application of nanodiamonds.
In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway
(2016-11-29)
Lin, Yu-Ling
;
Tsai, Nu-Man
;
Hsieh, Cheng-Hao
;
Ho, Shu-Yi
;
Chang, Jung
Cancer progression is associated with the development of antitumor autoantibodies in patients\' sera. Although passive treatment with antitumor antibodies has exhibited remarkable therapeutic efficacy, inhibitory effects on tumor progression by endogenous antitumor autoantibodies (EAAs) have been limited. In this study, we show that P4N, a derivative of the plant lignan nordihydroguaiaretic acid (NDGA), enhanced the production of EAAs and inhibited tumor growth at low noncytotoxic concentrations via its immunoregulatory activity. Intratumoral injection of P4N improved the quantity and quality of EAAs, and passive transfer of P4N-induced EAAs dramatically suppressed lung metastasis formation and prolonged the survival of mice inoculated with metastatic CT26 tumor cells. P4N-induced EAAs specifically recognized two surface antigens, 78-kDa glucose-regulated protein (GRP78) and F1F0 ATP synthase, on the plasma membrane of cancer cells. Additionally, P4N treatment led to B-cell proliferation, differentiation to plasma cells, and high titers of autoantibody production. By serial induction of autocrine and paracrine signals in monocytes, P4N increased B-cell proliferation and antibody production via the leukotriene A4 hydrolase (LTA4H)/activin A/B-cell activating factor (BAFF) pathway. This mechanism provides a useful platform for studying and seeking a novel immunomodulator that can be applied in targeting therapy by improving the quantity and quality of the EAAs.
Simple and highly efficient direct thiolation of the surface of carbon nanotubes
(2014)
Hsu, Ming-Hua
;
Chuang, Hong
;
Cheng, Fong-Yu
;
Huang, Ying-Pei
;
Han, Chien-Chung
We established a highly efficient and simple method to directly functionalize the surface of carbon nanotubes (CNTs) with thiol groups (-SH). The -SH groups on the surface of the CNTs were characterized using Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), elemental analysis (EA), and transmission electron microscopy (TEM). The TEM indicated that gold nanoparticles (Au NPs) or other metals can be attached to thiolated CNTs (CNT-SHs) through thiol-metal bonding. Hence, the proposed approach can be used for developing self-assembled materials, sensors, catalysts, and CNT nanodevices.
Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents
(2016-02-01)
Tsai, Chia-Ying
;
Kapoor, Mohit
;
Huang, Ying-Pei
;
Lin, Hui-Hsien
;
Liang, Yu-Chuan
In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using H-1-NMR, C-13-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 mu M to AGS, 4.4 mu M to HT-29 cells and 5.8 mu M to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 mu M to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.
Synthesis of Apolipoprotein B Lipoparticles to Deliver Hydrophobic/Amphiphilic Materials
(2013-08-14)
Chu, Hsueh-Liang
;
Cheng, Tsai-Mu
;
Chen, Hung-Wei
;
Chou, Fu-Hsuan
;
Chang, Yu-Chuan
To develop a drug delivery system (DDS), it is critical to address challenging tasks such as the delivery of hydrophobic and amphiphilic compounds, cell uptake, and the metabolic fate of the drug delivery carrier. Low-density lipoprotein (LDL) has been acknowledged as the human serum transporter of natively abundant lipoparticles such as cholesterol, triacylglycerides, and lipids. Apolipoprotein B (apo B) is the only protein contained in LDL, and possesses a binding moiety for the LDL receptor that can be internalized and degraded naturally by the cell. Therefore, synthetic/reconstituting apoB lipoparticle (rABL) could be an excellent delivery carrier for hydrophobic or amphiphilic materials. Here, we synthesized rABL in vitro, using full-length apoB through a five-step solvent exchange method, and addressed its potential as a DDS. Our rABL exhibited good biocompatibility when evaluated with cytotoxicity and cell metabolic response assays, and was stable during storage in phosphate-buffered saline at 4 degrees C for several months. Furthermore, hydrophobic superparamagnetic iron oxide nanoparticles (SPIONPs) and the anticancer drug M4N (tetra-O-methyl nordihydroguaiaretic acid), used as an imaging enhancer and lipophilic drug model, respectively, were incorporated into the rABL, leading to the formation of SPIONPs- and M4N- containing rABL (SPIO@rABL and M4N@rABL, respectively). Fourier transform infrared spectroscopy suggested that rABL has a similar composition to that of LDL, and successfully incorporated SPIONPs or M4N. SPIO@rABL presented significant hepatic contrast enhancement in T-2-weighted magnetic resonance imaging in BALB/c mice, suggesting its potential application as a medical imaging contrast agent. M4N@rABL could reduce the viability of the cancer cell line A549. Interestingly, we developed solution-phase high-resolution transmission electron microscopy to observe both LDL and SPIO@rABL in the liquid state. In summary, our LDL-based DDS, rABL, has significant potential as a novel DDS for hydrophobic and amphiphilic materials, with good cell internalization properties and metabolicity.