| 1. |
- Prachayasittikul, Veda, et al.
(author)
-
Computer-Aided Drug Design of Bioactive Natural Products.
- 2015
-
In: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1568-0266 .- 1873-4294. ; 15:18, s. 1780-800
-
Journal article (peer-reviewed)abstract
- Natural products have been an integral part of sustaining civilizations because of their medicinal properties. Past discoveries of bioactive natural products have relied on serendipity, and these compounds serve as inspiration for the generation of analogs with desired physicochemical properties. Bioactive natural products with therapeutic potential are abundantly available in nature and some of them are beyond exploration by conventional methods. The effectiveness of computational approaches as versatile tools for facilitating drug discovery and development has been recognized for decades, without exception, in the case of natural products. In the post-genomic era, scientists are bombarded with data produced by advanced technologies. Thus, rendering these data into knowledge that is interpretable and meaningful becomes an essential issue. In this regard, computational approaches utilize the existing data to generate knowledge that provides valuable understanding for addressing current problems and guiding the further research and development of new natural-derived drugs. Furthermore, several medicinal plants have been continuously used in many traditional medicine systems since antiquity throughout the world, and their mechanisms have not yet been elucidated. Therefore, the utilization of computational approaches and advanced synthetic techniques would yield great benefit to improving the world's health population and well-being.
|
|
| 2. |
- Prachayasittikul, Veda, et al.
(author)
-
Exploring the epigenetic drug discovery landscape
- 2017
-
In: Expert Opinion on Drug Discovery. - : TAYLOR & FRANCIS LTD. - 1746-0441 .- 1746-045X. ; 12:4, s. 345-362
-
Research review (peer-reviewed)abstract
- Introduction: Epigenetic modification has been implicated in a wide range of diseases and the ability to modulate such systems is a lucrative therapeutic strategy in drug discovery. Areas covered: This article focuses on the concepts and drug discovery aspects of epigenomics. This is achieved by providing a survey of the following concepts: (i) factors influencing epigenetics, (ii) diseases arising from epigenetics, (iii) epigenetic enzymes as druggable targets along with coverage of existing FDA-approved drugs and pharmacological agents, and (iv) drug repurposing/repositioning as a means for rapid discovery of pharmacological agents targeting epigenetics. Expert opinion: Despite significant interests in targeting epigenetic modifiers as a therapeutic route, certain classes of target proteins are heavily studied while some are less characterized. Thus, such orphan target proteins are not yet druggable with limited report of active modulators. Current research points towards a great future with novel drugs directed to the many complex multifactorial diseases of humans, which are still often poorly understood and difficult to treat.
|
|
| 3. |
|
|
| 4. |
- Boonpangrak, Somchai, et al.
(author)
-
Preparation of molecularly imprinted polymers using nitroxide-mediated living radical polymerization
- 2006
-
In: Biosensors & Bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 22:3, s. 349-354
-
Journal article (peer-reviewed)abstract
- The use of molecularly imprinted polymers (MIPs) in chemical and bioanalytical applications has been gaining in interest in recent years. Compared to their biological receptor counterparts, MIP's are easy to prepare, have long shelf stability and can be used under a variety of harsh conditions. The majority of MIPs currently used are produced by traditional free radical polymerization. One drawback with the use of standard free radical initiators is that little control can be exerted over the chemical processes that form the final imprinted cavities. In this study we set out to investigate the application of controlled (living) free radical polymerization to the preparation of MIPs. This was exemplified by the synthesis of cholesterol-imprinted bulk polymers by nitroxide-mediated polymerization (NMP). A sacrificial covalent bond was employed to maintain imprinting fidelity at elevated temperature. Selective uptake of cholesterol from solutions in hexane was studied with imprinted polymers prepared under different conditions. The imprinted hydrolyzed MIP prepared by NMP displayed higher selective cholesterol binding than that prepared by a traditional radical polymerization. (c) 2006 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Grey, Marie, et al.
(author)
-
A superoxide dismutase-human hemoglobin fusion protein showing enhanced antioxidative properties.
- 2009
-
In: The FEBS Journal. - : Wiley. - 1742-464X. ; 276:21, s. 6195-6203
-
Journal article (peer-reviewed)abstract
- Much of the toxicity of Hb has been linked to its redox activity; Hb may generate reactive oxygen species, such as the superoxide anion. Superoxide is intrinsically toxic, and superoxide dismutase (SOD) provides important cellular protection. However, if the Hb molecule is located outside the red blood cell, the normal protection systems involving SOD and catalase are no longer closely associated with it, exposing Hb and its cellular surroundings to oxidative damage. In order to produce less toxic Hb molecules, we have explored gene fusion to obtain homogeneous SOD-Hb conjugates. The chimeric protein was generated by coexpressing the human Hb alpha-chain/manganese SOD gene together with the beta-chain gene in Escherichia coli. We show that the engineered SOD-Hb fusion protein retains the oxygen-binding capacity and, moreover, decreases cytotoxic ferrylHb (HbFe(4+)) formation when challenged with superoxide radicals. The SOD-Hb fusion protein also exhibits a 44% lower autoxidation rate and higher thermal stability than Hb alone.
|
|
| 6. |
- Isarankura-Na-Ayudhya, Chartchalerm, et al.
(author)
-
Biochemical and Cellular Investigation of Vitreoscilla Hemoglobin (VHb) Variants Possessing Efficient Peroxidase Activity
- 2010
-
In: Journal of Microbiology and Biotechnology. - 1017-7825. ; 20:3, s. 532-541
-
Journal article (peer-reviewed)abstract
- Peroxidase-like activity of Vitreoscilla hemoglobin (VHb) has been recently disclosed. To maximize such activity, two catalytically conserved residues (histidine and arginine) found in the distal pocket of peroxidases have successfully been introduced into that of the VHb. A 15-fold increase in catalytic constant (k(cat)) was obtained in P54R variant, which was presumably attributable to the lower rigidity and higher hydrophilicity of the distal cavity arising from substitution of proline to arginine. None of the modifications altered the affinity towards either H2O2 or ABTS substrate. Spectroscopic studies revealed that VHb variants harboring the T29H mutation apparently demonstrated a spectral shift in both ferric and ferrous forms (406-408 to 411 nm, and 432 to 424-425 nm, respectively). All VHb proteins in the ferrous state had a lambda(soret) peak at 419 nm following the carbon monoxide (CO) binding. Expression of the P54R mutant mediated the downregulation of iron superoxide dismutase (FeSOD) as identified by two-dimensional gel electrophoresis (2-DE) and peptide mass fingerprinting (PMF). According to the high peroxidase activity of P54R, it could effectively eliminate autoxidation-derived H2O2, which is a cause of heme degradation and iron release. This decreased the iron availability and consequently reduced the formation of the Fe2+-ferric uptake regulator protein (Fe2+-Fur), an inducer of FeSOD expression.
|
|
| 7. |
- Isarankura-Na-Ayudhya, Chartchalerm, et al.
(author)
-
Computational Insights on Sulfonamide Imprinted Polymers
- 2008
-
In: Molecules. - : MDPI AG. - 1420-3049. ; 13:12, s. 3077-3091
-
Journal article (peer-reviewed)abstract
- Molecular imprinting is one of the most efficient methods for preparing synthetic receptors that possess user defined recognition properties. Despite general success of non-covalent imprinting for a large variety of templates, some groups of compounds remain difficult to tackle due to their structural complexity. In this study we investigate preparation of molecularly imprinted polymers that can bind sulfonamide compounds, which represent important drug candidates. Compared to the biological system that utilizes metal coordinated interaction, the imprinted polymer provided pronounced selectivity when hydrogen bond interaction was employed in an organic solvent. Computer simulation of the interaction between the sulfonamide template and functional monomers pointed out that although methacrylic acid had strong interaction energy with the template, it also possessed high non-specific interaction with the solvent molecules of tetrahydrofuran as well as being prone to self-complexation. On the other hand, 1-vinylimidazole was suitable for imprinting sulfonamides as it did not cross-react with the solvent molecules or engage in self-complexation structures.
|
|
| 8. |
- Isarankura-Na-Ayudhya, Chartchalerm, et al.
(author)
-
Engineering of a novel chimera of superoxide dismutase and Vitreoscilla hemoglobin for rapid detoxification of reactive oxygen species
- 2010
-
In: Journal of Bioscience and Bioengineering. - : Elsevier BV. - 1347-4421 .- 1389-1723. ; 110:6, s. 633-637
-
Journal article (peer-reviewed)abstract
- The genes encoding human manganese superoxide dismutase (MnSOD) and Vitreoscilla hemoglobin (VHb) were fused inframe to generate a bifunctional enzyme that possessed MnSOD and peroxidase-like activities. At neutral pH, the coupling of the SOD and peroxidase reactions revealed that the bifunctional enzyme exhibited a 2.5 times shorter transient period and a 1.67 times higher reaction rate at steady-state conditions. Furthermore, the catalytic rate of the bifunctional enzyme was not affected as much by the external H2O2 scavenger catalase. This indicates that the bifunctional protein possesses a greater antioxidant capability, which is possibly due to the close proximity between the active site of MnSOD and the heme moiety of VHb. Our findings not only provide insight into the synergistic functions of SOD and peroxidase but also could potentially be used to develop novel therapeutic agents with more efficient O-2 carrying capability. (C) 2010, The Society for Biotechnology, Japan. All rights reserved.
|
|
| 9. |
- Lapins, Maris, et al.
(author)
-
A Unified Proteochemometric Model for Prediction of Inhibition of Cytochrome P450 Isoforms
- 2013
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6, s. e66566-
-
Journal article (peer-reviewed)abstract
- A unified proteochemometric (PCM) model for the prediction of the ability of drug-like chemicals to inhibit five major drug metabolizing CYP isoforms (i.e. CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) was created and made publicly available under the Bioclipse Decision Support open source system at www.cyp450model.org. In regards to the proteochemometric modeling we represented the chemical compounds by molecular signature descriptors and the CYP-isoforms by alignment-independent description of composition and transition of amino acid properties of their protein primary sequences. The entire training dataset contained 63 391 interactions and the best PCM model was obtained using signature descriptors of height 1, 2 and 3 and inducing the model with a support vector machine. The model showed excellent predictive ability with internal AUC = 0.923 and an external AUC = 0.940, as evaluated on a large external dataset. The advantage of PCM models is their extensibility making it possible to extend our model for new CYP isoforms and polymorphic CYP forms. A key benefit of PCM is that all proteins are confined in one single model, which makes it generally more stable and predictive as compared with single target models. The inclusion of the model in Bioclipse Decision Support makes it possible to make virtual instantaneous predictions (∼100 ms per prediction) while interactively drawing or modifying chemical structures in the Bioclipse chemical structure editor.
|
|
| 10. |
- Lawung, Ratana, et al.
(author)
-
Antibiograms and Randomly Amplified Polymorphic DNA-Polymerase Chain Reactions (RAPD-PCR) as Epidemiological Markers of Gonorrhea
- 2010
-
In: Journal of Clinical Laboratory Analysis. - : Wiley. - 1098-2825 .- 0887-8013. ; 24:1, s. 31-37
-
Journal article (peer-reviewed)abstract
- The development of antimicrobial resistance of Neisseria gonorrhoeae arising from wide dissemination of resistant clones is a major global health problem. In this study, a total of 235 isolates of N. gonorrhoeae isolated from patients of Bangrak Hospital were tested for their antibiotic susceptibilities to penicillin, norfloxacin, ofloxacin, ciprofloxacin, spectinomycin, and ceftriaxone. Mutation (Ser-91) in the quinolone resistance determining regions of gyrA and random amplification of the polymorphic DNA polymerase chain reaction (RAPD-PCR) were examined from 145 isolates. Among these, 55 isolates were obtained during January-March 2000, 46 isolates during January-March 2002, and 44 isolates during October-December 2002. The occurrence of combination resistance between penicillin and quinolone was 20% in January-March 2000, which was increased to 57.8% during the period of October-December 2002 (P<0.0001). Mutation of Ser-91 in gyrA could be directly linked with the resistance or declining of susceptibility to ciprofloxacin. Using RAPD-PCR, we could classify the 145 isolates into 4 and 5 groups by primers D11344 (5'-AGTGAATTCGCGGTGAGATGCCA-3') and D8635 (5'-GAGCGGCCAAAGGGAG-CA GAC-3'), respectively. Combination of the data obtained from these two primers produced 11 fingerprint groups. Our findings conclude that monitoring of the Ser-91 mutation of gyrA and RAPD-PCR methods are most useful for epidemiological screening. (C) 2010 Wiley-Liss, Inc.
|
|
