• Genomics & Informatics
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• v.21 no.1
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• pp.6.1-6.8
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• 2023

Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.91-96
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• 1997

General steps in the discovery and development of novel drugs in the United States are presented. The first step is the discovery of novel drugs. Brief histories and mechanisms of a few novel drugs in the American market are outlined. In this presentation preclinical animal toxicologic studies (drug safety evaluateion) are emphasized in regard to drug development. When preclinical animal studies have defined the toxicity and the doses at which it occurs an Investigational new Drug Application (IND) is submitted to the Food and Drug Administration (FDA) An IND notifies the FDA the intention to begin testing a novel drug in human subjects.

• Journal of Microbiology and Biotechnology
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• v.29 no.5
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• pp.713-720
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• 2019

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.

• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.171-177
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• 2019

Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p < 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.237.3-238
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• 2003

Carbonucleosides has extensively been studied as a promising anti-viral agents having chemical and metabolical stability. As yet there are no rules relating the structures of carbocyclic nucleosides to their therapeutic activity. although trends among certain kinds of structure have been tentatively put forward. In our research program for discovery of anti-viral drugs, the novel cyclobutyl nucleosides can be expected to be potential antiviral drugs as analogues of cyclobut-A, anti-HBV agent. (omitted)

• Journal of Veterinary Science
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• v.21 no.2
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• pp.37.1-37.5
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• 2020

Poultry red mites (PRMs), Dermanyssus gallinae, are one of the most harmful ectoparasites of laying hens. Because of their public health impact, safe, effective methods to eradicate PRMs are greatly needed. Carbon dioxide (CO₂) was shown to eradicate phytophagous mites; however, there is no evidence that PRMs can be eradicated by CO₂. Thus, the efficacy of CO₂, applied by direct-spraying and dry ice-generated exposure, for eradicating PRMs was investigated. Both treatments eradicated > 85% of PRMs within 24 h and 100% of PRMs by 120 h of post-treatment. Therefore, these novel approaches may be useful for eradicating PRMs in clinical settings.

• Korean Journal of Clinical Pharmacy
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• v.33 no.4
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• pp.290-304
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• 2023

Background: Innovative Alzheimer's disease drugs received approval in the United States in 2021 and 2023. This study aims to assess the safety and efficacy of these novel treatments, elucidate their mechanisms of action, and compare their impact on cognitive function improvement with approved drugs. Methods: We conducted a comprehensive search of pivotal clinical studies related to Alzheimer's disease treatments in PubMed/Medline, Embase, and the Cochrane Library databases from January 1st, 2020 to December 31st, 2022. Meta-analysis was performed using RevMan 5.4 software. Results: A total of 14 studies were included in this systematic review. When compared to the placebo, the new drugs did not exhibit a statistically significant effect on MMSE (Mini-Mental State Examination) (mean difference= -0.04, 95% confidence intervals [CIs]: -0.31, 0.23, N=3662, I²=0%). However, they demonstrated a significant impact on ADAS-cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) (standardized mean difference= -0.15, 95% CIs: -0.2, -0.1, N=6710, I²=17%). When compared to the approved drugs, the new drugs showed a statistically significantly lower effect on MMSE (test for subgroup difference Chi²=23.13, N = 5870, p<0.00001) but showed only a trend of decreased efficacy on ADAS-cog (Chi²=1.16, N = 8670, p=0.28). Conclusion: New drugs yielded diverse clinical endpoint results compared to the placebo, and in comparison to existing approved drugs, they exhibited lower efficacy in improving cognitive function. The safety profile of these new drugs, as reported in clinical trials, was generally well-tolerated.

• International Journal of Computer Science & Network Security
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• v.22 no.9
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• pp.258-270
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• 2022

Cancer has become a common disease for the past two decades throughout the globe and there is significant increase of cancer among women. Breast cancer and ovarian cancers are more prevalent among women. Majority of the patients approach the physicians only during their final stage of the disease. Early diagnosis of cancer remains a great challenge for the researchers. Although several drugs are being synthesized very often, their multi-benefits are less investigated. With millions of drugs synthesized and their data are accessible through open repositories. Drug repurposing can be done using machine learning techniques. We propose a feature selection technique in this paper, which is novel that generates multiple populations for the grey wolf algorithm and classifies breast cancer drugs efficiently. Leukemia drug dataset is also investigated and Multilayer perceptron achieved 96% prediction accuracy. Three supervised machine learning algorithms namely Random Forest classifier, Multilayer Perceptron and Support Vector Machine models were applied and Multilayer perceptron had higher accuracy rate of 97.7% for breast cancer drug classification.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.299-310
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• 2023

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.624-626
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• 2006

Four known butenolides were isolated from the ethyl acetate extracts of the culture broth of the marine-derived bacterium, Streptoverticillium luteoverticillatum, by bioassay-guided fractionation. The structures were identified on the basis of spectral data. The absolute configuration of compound (1) was determined by CD spectrum for the first time. Compounds 1-4 showed in vitro cytotoxicity against the murine lymphoma P388 and human leukemia K562 cell lines. This is the first report on the isolation of butenolides from the marine bacterium, Streptoverticillium luteoverticillatum, and their cytotoxic activities.