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Publication Metadata only Metal complexes of uracil derivatives with cytotoxicity and superoxide scavenging activity(2012-03-01) Supaluk Prachayasittikul; Apilak Worachartcheewan; Ratchanok Pingaew; Thummaruk Suksrichavalit; Chartchalerm Isarankura-Na-Ayudhya; Somsak Ruchirawat; Virapong Prachayasittikul; Srinakharinwirot University; Mahidol University; Chulabhorn Research Institute5-Substituted uracils were reported to be important core structure of diverse therapeutics. Herein, novel mixed ligand transition metal (Mn, Cu, Ni) complexes of 5-iodouracil (5Iu) with 8-hydroxyquinoline or 8HQ (1-3) and 5-nitrouracil (5Nu) with 8...HQ (4-6) have been synthesized. The metal complexes 1-6 exert significant cytotoxicity against HepG2, A-549, HuCCA-1 and MOLT-3 cell lines. Particularly, the cytotoxicities of tested complexes against HepG2 cells show their IC 50 values lower thanPublication Metadata only Synthesis, anticancer activity and QSAR study of 1,4-naphthoquinone derivatives(2014-09-12) Veda Prachayasittikul; Ratchanok Pingaew; Apilak Worachartcheewan; Chanin Nantasenamat; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; Mahidol University; Srinakharinwirot University; Chulabhorn Research Institute; Chulabhorn Graduate Institute; Ministry of Educationthe HepG2, HuCCA-1 and A549 cell lines was found to be m-acetylphenylamino-1,4-naphthoquinone (8) affording IC50values of 4.758, 2.364 and 12.279 μM, respectively. On the other hand, p-acetylphenylamino-1,4-naphthoquinone (9) exhibited the most potent....1881. The effects of substituents at the 2-amino position on the naphthoquinone core structure and its corresponding influence on the cytotoxic activity were investigated by virtually constructing additional 1,4-naphthoquinone compounds (13-36) for which cytotoxicPublication Open Access Discovery of novel 1,2,3-triazole derivatives as anticancer agents using QSAR and in silico structural modification(2015-10-05) Veda Prachayasittikul; Ratchanok Pingaew; Nuttapat Anuwongcharoen; Apilak Worachartcheewan; Chanin Nantasenamat; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong 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 InformaticsConsiderable attention has been given on the search for novel anticancer drugs with respect to the disease sequelae on human health and well-being. Triazole is considered to be an attractive scaffold possessing diverse biological activities. Structural modification on the privileged structures is noted as an effective strategy towards successful design and development of novel drugs. The quantitative structure–activity relationships (QSAR) is well-known as a powerful computational tool to facilitate the discovery of potential compounds. In this study, a series of thirty-two 1,2,3-triazole derivatives (1–32) together with their experimentally measured cytotoxic activities against four cancer cell lines i.e., HuCCA-1, HepG2, A549 and MOLT-3 were used for QSAR analysis. Four QSAR models were successfully constructed with acceptable predictive performance affording RCV ranging from 0.5958 to 0.8957 and RMSE CV ranging from 0.2070 to 0.4526. An additional set of 64 structurally modified triazole compounds (1A–1R, 2A–2R, 7A–7R and 8A–8R) were constructed in silico and their predicted cytotoxic activities were obtained using the constructed QSAR models. The study suggested crucial moieties and certain properties essential for potent anticancer activity and highlighted a series of promising compounds (21, 28, 32, 1P, 8G, 8N and 8Q) for further development as novel triazole-based anticancer agents.Publication Open Access Copper Complexes of Nicotinic-Aromatic Carboxylic Acids as Superoxide Dismutase Mimetics(Mahidol University, 2008) Thummaruk Suksrichavalit; Supaluk Prachayasittikul; Theeraphon Piacham; Chartchalerm Isarankura-Na-Ayudhya; Chanin Nantasenamat; Virapong Prachayasittikul) at the B3LYP/LANL2DZ level of theory. Interestingly, the SOD activity of the copper complex CuNA/Ph was positively correlated with the electron affinity (EA) value. The two quantum chemical parameters, highest occupied molecular orbital (HOMO) and lowest... shown to possess the lowest HOMO energy. These findings demonstrate a great potential for the development of value-added metallovitamin-based therapeutics.Publication Open Access Derivatives (halogen, nitro and amino) of 8-hydroxyquinoline with highly potent antimicrobial and antioxidant activities(2016-07) Rungrot Cherdtrakulkiat; Somchai Boonpangrak; Nujarin Sinthupoom; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology; Mahidol University. Faculty of Medical Technology. Center for Innovation Development and Technology Transfer; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informaticsagainst Gram-positive bacteria including diploid fungi and yeast with MIC values in the range of 3.44-13.78 μM. Moreover, the halogenated 8HQ, especially 7-bromo-8HQ (4) and clioquinol (6), displayed a high antigrowth activity against Gram-negative... of P. aeruginosa with the MIC value of 84.14 μM; cloxyquin (3) showed a strong activity against L. monocytogenes and P. shigelloides with MIC values of 5.57 and 11.14 μM, respectively. Most compounds displayed an antioxidant activity. Specifically, 5Publication Open Access Bioactive azafluorenone alkaloids from polyalthia debilis (Pierre) finet and gagnep(2009) Supaluk Prachayasittikul; Patumporn Manam; Maneekarn Chinworrungsee; Chartchalerm Isarankura-Na-Ayudhya; Somsak Ruchirawat; Virapong PrachayasittikulThis study investigated bioactive extracts of Polyalthia debilis (Annonaceae) with antimicrobial, antimalarial and cytotoxic activities. Extensive chromatographic isolations provided azafluorenone alkaloids; onychine (1) and 7-methoxyonychine (2) together with a mixture of β–sitosterol and stigmasterol. The two alkaloids were isolated from the P. debilis for the first time. Isolated fractions containing a mixture of triterpenoids (C7, C8 and C9) exhibited the most potent antimicrobial activity against many bacterial strains with minimum inhibitory concentration of 64 μg/mL. Fractions with antimalarial and cytotoxic activities were also observed. The findings suggest the potential use of P. debilis in medicinal applications.Publication Open Access Synthesis of a “clickable” Angiopep-conjugated p-coumaric acid for brain-targeted delivery(2014-08-19) Thummaruk Suksrichavalit; Supaluk Prachayasittikul; Virapong Prachayasittikul; Chartchalerm Isarankura Na Ayudhya; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics; Mahidol University. Faculty of Medical Technology. Department of Clinical Chemistry; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied TechnologyOverexpression of free radicals in the brain is emerging as important markers in the etiology of neurodegenerative diseases including Parkinson’s disease, Alzheimer’s disease, and stroke. Numerous antioxidants with protective effect on neuronal injuries under oxidative stress are often limited to penetrate the blood–brain barrier (BBB). Angiopep-2 is the ligand of low-density lipoprotein receptor-related protein expressed on the BBB possessing high transcytosis capacity and parenchymal accumulation. In this study, novel Angiopep-conjugated p-coumaric acid (3) was synthesized, using the Click chemistry, as a potential antioxidant for the protection of the brain under oxidative stress. The clickable Angiopep (3) was synthesized by Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction of the terminal acetylene-modified Angiopep and azide of p-coumaric acid. The Angiopep-conjugated compound (3) showed antioxidant potency and non-cytotoxic effect toward brain endothelial cells (BECs). Obviously, the penetration and BECs protection of 3 were higher than that of the unconjugated p-coumaric acid. The results establish the bio-conjugation of antioxidant and Angiopep with enhanced protective effect on the BECs under oxidative stress. The findings provide great potential for the development of neurotherapeutics with increased brain penetration.Publication Open Access Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells(2015-04-08) Waraporn Chan-on; Nguyen Thi Bich Huyen; Napat Songtawee; Wilasinee Suwanjang; Supaluk Prachayasittikul; Virapong 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: Fork head box M1 (FoxM1) is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA). A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ) and nitroxoline (NQ), represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells. Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium (MTS assay). Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction. Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment, expression of oncogenic FoxM1 was markedly decreased concomitant with downregulation of various FoxM1’s downstream targets including cdc25b, CENP-B, and survivin. In addition, the compounds distinctly impaired HuCCT1 migration as well as inhibited expression of matrix metalloproteinase (MMP)-2 and MMP-9. Conclusion: Collectively, this study reports for the first time the anticancer effects of CQ and NQ against CCA cells, and highlights new insights into the mechanism of actions of the quinoline-based compounds to disrupt FoxM1 signaling.