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Publication Metadata only Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling(2016-02-01) Sumitra Miriyala; Chadinee Thippakorn; Luksana Chaiswing; Yong Xu; Teresa Noel; Artak Tovmasyan; Ines Batinic-Haberle; Craig W. Vander Kooi; Wang Chi; Ahmed Abdel Latif; Manikandan Panchatcharam; Virapong Prachayasittikul; D. Allan Butterfield; Mary Vore; Jeffrey Moscow; Daret K.St Clair; University of Kentucky; Louisiana State University in Shreveport; Mahidol University; University of Wisconsin Madison; Duke University Medical Center; University of Kentucky HealthCarerole of HNE with important consequences for mitochondrial stress signaling, heart failure, and the side effects of cancer therapy....© 2015 Elsevier Inc. All rights reserved. Cardiovascular complications are major side effects of many anticancer drugs. Accumulated evidence indicates that oxidative stress in mitochondria plays an important role in cardiac injury, but howPublication Metadata only Synthesis and neuroprotective effects of novel chalcone-triazole hybrids(2020-12-01) Pichjira Sooknual; Ratchanok Pingaew; Kamonrat Phopin; Waralee Ruankham; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; South Carolina Commission on Higher Education; Chulabhorn Research Institute; Mahidol University; Srinakharinwirot University; Chulabhorn Graduate Institute) was synthesized and evaluated for their biological properties including cytotoxicity, antioxidant, anti-apoptosis, and neuroprotection using SH-SY5Y cells. The results showed that 6a and 6e provided neuroprotection in oxidative stress-induced neuronal cell damage.... Both compounds significantly improved the morphology of neurons and obviously increased cell survival rate of neuronal cells induced by oxidative stress. Additionally, 6a and 6e counteracted H2O2‑induced mitochondrial dysfunction, which was supportedPublication Open Access Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives(2014-08-14) Veda Prachayasittikul; Ratchanok Pingaew; Virapong Prachayasittikul; Chanin Nantasenamat; Somsak Ruchirawat; Supaluk Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical InformaticsPurpose: Estrogens play important roles in the pathogenesis and progression of breast cancer as well as estrogen-related diseases. Aromatase is a key enzyme in the rate-limiting step of estrogen production, in which its inhibition is one strategy for controlling estrogen levels to improve prognosis of estrogen-related cancers and diseases. Herein, a series of metal (Mn, Cu, and Ni) complexes of 8-hydroxyquinoline (8HQ) and uracil derivatives (4–9) were investigated for their aromatase inhibitory and cytotoxic activities. Methods: The aromatase inhibition assay was performed according to a Gentest™ kit using CYP19 enzyme, wherein ketoconazole and letrozole were used as reference drugs. The cytotoxicity was tested on normal embryonic lung cells (MRC-5) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Only Cu complexes (6 and 9) exhibited aromatase inhibitory effect with IC50 0.30 and 1.7 µM, respectively. Cytotoxicity test against MRC-5 cells showed that Mn and Cu complexes (5 and 6), as well as free ligand 8HQ, exhibited activity with IC50 range 0.74–6.27 µM. Conclusion: Cu complexes (6 and 9) were found to act as a novel class of aromatase inhibitor. Our findings suggest that these 8HQ–Cu–uracil complexes are promising agents that could be potentially developed as a selective anticancer agent for breast cancer and other estrogen-related diseases.Publication Open Access Molecular basis of human cerebral malaria development(2016) Saw Thu Wah; Hathairad Hananantachai; Usanee Kerdpin; Chotiros Plabplueng; Virapong Prachayasittikul; Pornlada Nuchnoi; Mahidol University. Faculty of Medical Technology. Department of Clinical Microscopy; Mahidol University. Faculty of Medical Technology. Center for Research and InnovationCerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.Publication Open Access Origin of aromatase inhibitory activity via proteochemometric modeling(2016-04) Saw Simeon; Ola Spjuth; Maris Lapins; Chanin Nantasenamat; Jarl ES Wikberg; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical InformaticsAromatase, the rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure-activity relationships and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents.Publication Open Access Molecular modeling of the human hemoglobin-haptoglobin complex sheds light on the protective mechanisms of haptoglobin.(Mahidol University, 2013-04) Chanin Nantasenamat; Virapong Prachayasittikul; Leif Bulow; Mahidol University. Faculty of Medical TechnologyHemoglobin (Hb) plays a critical role in human physiological function by transporting O2. Hb is safe and inert within the confinement of the red blood cell but becomes reactive and toxic upon hemolysis. Haptoglobin (Hp) is an acute-phase serum protein that scavenges Hb and the resulting Hb-Hp complex is subjected to CD163-mediated endocytosis by macrophages. The interaction between Hb and Hp is extraordinarily strong and largely irreversible. As the structural details of the human Hb-Hp complex are not yet available, this study reports for the first time on insights of the binding modalities and molecular details of the human Hb-Hp interaction by means of protein-protein docking. Furthermore, residues that are pertinent for complex formation were identified by computational alanine scanning mutagenesis. Results revealed that the surface of the binding interface of Hb-Hp is not flat and protrudes into each binding partner. It was also observed that the secondary structures at the Hb-Hp interface are oriented as coils and α-helices. When dissecting the interface in more detail, it is obvious that several tyrosine residues of Hb, particularly β145Tyr, α42Tyr and α140Tyr, are buried in the complex and protected from further oxidative reactions. Such finding opens up new avenues for the design of Hp mimics which may be used as alternative clinical Hb scavengers.