Chulabhorn Research Institute

Chulabhorn, Thailand

Chulabhorn Research Institute

Chulabhorn, Thailand

Chulabhorn Research Institute is a biomedical and chemistry research institute in Bangkok, Thailand. Initiated by Princess Chulabhorn in 1987, the institute was established as an independent agency funded by the Thai government.Today, the institute operates 9 laboratories in biochemistry, biotechnology, medicinal chemistry, chemical carcinogenesis, environmental toxicology, immunology, natural products, organic synthesis and pharmacology. Besides research, the institute also offers various trainings as well as master's and doctoral degree programs in Environmental Toxicology, Technology and Management.In addition to the existing units and programs, the Chulabhorn Cancer Center and Chulabhorn Graduate School are scheduled to open in 2007. Wikipedia.

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Ruchirawat S.,Chulabhorn Research Institute
Current topics in medicinal chemistry | Year: 2014

Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review.

Prachayasittikul V.,Mahidol University | Prachayasittikul S.,Mahidol University | Ruchirawat S.,Chulabhorn Research Institute
Drug Design, Development and Therapy | Year: 2013

Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure-activity relationships. © 2013 Prachayasittikul et al.

Dubbs J.M.,Chulabhorn Research Institute | Mongkolsuk S.,Chulabhorn Research Institute | Mongkolsuk S.,Mahidol University
Journal of Bacteriology | Year: 2012

The ability to maintain intracellular concentrations of toxic reactive oxygen species (ROS) within safe limits is essential for all aerobic life forms. In bacteria, as well as other organisms, ROS are produced during the normal course of aerobic metabolism, necessitating the constitutive expression of ROS scavenging systems. However, bacteria can also experience transient high-level exposure to ROS derived either from external sources, such as the host defense response, or as a secondary effect of other seemingly unrelated environmental stresses. Consequently, transcriptional regulators have evolved to sense the levels of ROS and coordinate the appropriate oxidative stress response. Three well-studied examples of these are the peroxide responsive regulators OxyR, PerR, and OhrR. OxyR and PerR are sensors of primarily H2O2, while OhrR senses organic peroxide (ROOH) and sodium hypochlorite (NaOCl). OxyR and OhrR sense oxidants by means of the reversible oxidation of specific cysteine residues. In contrast, PerR senses H2O2 via the Fe-catalyzed oxidation of histidine residues. These transcription regulators also influence complex biological phenomena, such as biofilm formation, the evasion of host immune responses, and antibiotic resistance via the direct regulation of specific proteins. © 2012, American Society for Microbiology.

Sandee D.,University of California at San Francisco | Sandee D.,Chulabhorn Research Institute | Miller W.L.,University of California at San Francisco
Endocrinology | Year: 2011

P450 oxidoreductase (POR) is a two-flavin protein that reduces microsomal P450 enzymes and some otherproteins. Preparation of active bacterially expressed human POR for biochemical studies has been difficult because membrane-bound proteins tend to interact with column matrices. To reduce column-protein interactions and permit more vigorous washing, human POR lacking 27 N-terminal residues (N-27 POR) was modified to carry a C-terminal Gly3His6-tag (N-27 POR-G3H6). When expressed in Escherichia coli, N-27 POR-G3H6 could be purified to apparent homogeneity by a modified, single-step nickel-nitrilotriacetic acid affinity chromatography, yielding 31 mg POR per liter of culture, whereas standard purification of native N-27 POR required multiple steps, yielding 5 mg POR per liter. Both POR proteins had absorption maxima at 375 and 453 nm and both reduced cytochrome c with indistinguishable specific activities. Using progesterone as substrate for bacterially expressed purified human P450c17, the Michaelis constant for 17α-hydroxylase activity supported by N-27 POR or N-27 POR-G3H6 were 1.73 or 1.49 μM, and the maximal velocity was 0.029 or 0.026 pmol steroids per picomole P450 per minute, respectively. Using 17-hydroxypregnenolone as the P450c17 substrate, the Michaelis constant for 17,20 lyase activity using N-27 POR or N-27 POR-G3H6 was 1.92 or 1.89 μM and the maximal velocity was 0.041 or 0.042 pmol steroid per picomole P450 per minute, respectively. Thus, N-27 POR-G3H6 is equally active as native N-27 POR. This expression and purification system permits the rapid preparation of large amounts of highly pure, biologically active POR and may be generally applicable for the preparation of membrane-bound proteins. Copyright © 2011 by The Endocrine Society.

Thetsrimuang C.,Mahasarakham University | Khammuang S.,Mahasarakham University | Chiablaem K.,Chulabhorn Research Institute | Srisomsap C.,Chulabhorn Research Institute | Sarnthima R.,Mahasarakham University
Food Chemistry | Year: 2011

Crude polysaccharides of mature fresh and dried fruit bodies and dried mycelia of Lentinus polychrous Lév. were evaluated for their antioxidant properties and cancer cell line cytotoxicity. The crude polysaccharides were in yields of 39.0-97.5 mg/g dry weight of sample. Trolox equivalent values in scavenging abilities of those crude polysaccharides against both 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid (ABTS+) radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals were in the range of 53.4-131 and 6.4-38.8 μmol trolox/g dwt of extract, respectively, whereas values of reducing power were in the range 27.6-54.9 μmol trolox/g dwt of extract. Scavenging ability and reducing power of these crude polysaccharide extracts were in the descending order of mycelia > dried fruit bodies > fresh fruit bodies. In vitro cytotoxicity, determined with the crude polysaccharides of fresh and dried fruit bodies of the fungus at a concentration of 1 mg/ml, by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) method, showed cytotoxic effects of about 38% and 45%, respectively, against the human breast adenocarcinoma cell line (MCF-7). This mushroom might be a good source of bioactive compounds for cancer prevention. © 2011 Elsevier Ltd. All rights reserved.

Au W.W.,University of Texas Medical Branch | Giri A.K.,Indian Institute of Chemical Technology | Ruchirawat M.,Chulabhorn Research Institute
International Journal of Hygiene and Environmental Health | Year: 2010

A variety of biomarkers have been used to monitor exposed populations to determine potential health hazards from their exposure to environmental toxic agents. However, the majority of these biomarkers have been focused onto the identification of biological damage from the exposure. Therefore, there is a need to develop functional biomarkers that can identify exposure-induced functional deficiencies. More importantly, these deficiencies should be positioned along pathways that are responsible for the development of specific diseases. One of such pathways belongs to the extensive and complex DNA-repair machinery. The machinery thus becomes a large target for damage from environmental toxic agents. The hypothesis is that damage to any component of a repair pathway will interfere with the pathway-specific repair activities. Therefore, when cells from exposed populations are challenged with a DNA-damaging agent in vitro, the in vivo exposure-induced repair deficiency will be dramatically amplified and the deficiency will be detectable in a challenge assay as increased chromosome aberrations, micronuclei or un-repaired DNA strand breaks. The challenge assay has been used in different laboratories to show that a variety of exposed populations (with exposure to air pollutants, arsenic, benzene, butadiene, cigarette smoke, incense smoke, lead, mercury, pesticides, uranium or xylene but not to low concentrations of air pollutants or butadiene) expressed abnormal challenge response. The predicted health consequences of some of these studies have also been validated. Therefore, the challenge assay is a useful functional biomarker for population studies. Details of the challenge assay and its application will be presented in this review. © 2009 Elsevier GmbH. All rights reserved.

Fearnley S.P.,City University of New York | Thongsornkleeb C.,Chulabhorn Research Institute
Journal of Organic Chemistry | Year: 2010

Intramolecular Diels-Alder cycloaddition of N-substituted oxazolone triene I allows direct entry to the functionalized octahydroquinoline II. Further manipulation of this framework by stereo- and regioselective introduction of the 5-methyl substituent, followed by excision of the carbamate, yields (±)-2-epi-pumiliotoxin C. © 2009 American Chemical Society.

Chittasupho C.,Srinakharinwirot University | Lirdprapamongkol K.,Chulabhorn Research Institute | Kewsuwan P.,Thailand Institute of Nuclear Technology | Sarisuta N.,Thammasat University
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2014

Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system. © 2014 Elsevier B.V. All rights reserved.

Tolins M.,Chulabhorn Research Institute | Tolins M.,Mount Sinai School of Medicine | Ruchirawat M.,Chulabhorn Research Institute | Landrigan P.,Mount Sinai School of Medicine
Annals of Global Health | Year: 2014

Background More than 200 million people worldwide are chronically exposed to arsenic. Arsenic is a known human carcinogen, and its carcinogenic and systemic toxicity have been extensively studied. By contrast, the developmental neurotoxicity of arsenic has been less well described. The aim of this review was to provide a comprehensive review of the developmental neurotoxicity of arsenic. Methods We reviewed the published epidemiological and toxicological literature on the developmental neurotoxicity of arsenic. Results Arsenic is able to gain access to the developing brain and cause neurotoxic effects. Animal models link prenatal and early postnatal exposure to reduction in brain weight, reductions in numbers of glia and neurons, and alterations in neurotransmitter systems. Animal and in vitro studies both suggest that oxidative stress may be a mechanism of arsenic neurotoxicity. Fifteen epidemiological studies indicate that early life exposure is associated with deficits in intelligence and memory. These effects may occur at levels of exposure below current safety guidelines, and some neurocognitive consequences may become manifest only later in life. Sex, concomitant exposures, and timing of exposure appear to modify the developmental neurotoxicity of arsenic. Four epidemiological studies failed to show behavioral outcomes of arsenic exposure. Conclusions The published literature indicates that arsenic is a human developmental neurotoxicant. Ongoing and future prospective birth cohort studies will allow more precise definition of the developmental consequences of arsenic exposure in early life.

Prapagdee B.,Mahidol University | Chanprasert M.,Mahidol University | Mongkolsuk S.,Mahidol University | Mongkolsuk S.,Chulabhorn Research Institute
Chemosphere | Year: 2013

Micrococcus sp. MU1 and Klebsiella sp. BAM1, the cadmium-resistant plant growth-promoting rhizobacteria (PGPR), produce high levels of indole-3-acetic acid (IAA) during the late stationary phase of their growth. The ability of PGPR to promote root elongation, plant growth and cadmium uptake in sunflowers (Helianthus annuus) was evaluated. Both species of bacteria were able to remove cadmium ions from an aqueous solution and enhanced cadmium mobilization in contaminated soil. Micrococcus sp. and Klebsiella sp. use aminocyclopropane carboxylic acid as a nitrogen source to support their growth, and the minimum inhibitory concentrations of cadmium for Micrococcus sp. and Klebsiella sp. were 1000 and 800. mM, respectively. These bacteria promoted root elongation in H. annuus seedlings in both the absence and presence of cadmium compared to uninoculated seedlings. Inoculation with these bacteria was found to increase the root lengths of H. annuus that had been planted in cadmium-contaminated soil. An increase in dry weight was observed for H. annuus inoculated with Micrococcus sp. Moreover, Micrococcus sp. enhanced the accumulation of cadmium in the root and leaf of H. annuus compared to untreated plants. The highest cadmium accumulation in the whole plant was observed when the plants were treated with EDTA following the treatment with Micrococcus sp. In addition, the highest translocation of cadmium from root to the above-ground tissues of H. annuus was found after treatment with Klebsiella sp. in the fourth week after planting. Our results show that plant growth and cadmium accumulation in H. annuus was significantly enhanced by cadmium-resistant PGPRs, and these bacterial inoculants are excellent promoters of phytoextraction for the rehabilitation of heavy metal-polluted environments. © 2013 Elsevier Ltd.

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