• Bulletin of the Korean Chemical Society
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• 제32권3호
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• pp.1000-1006
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• 2011

The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged $IC_{50}$ value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold.

• Genomics & Informatics
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• 제19권1호
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• pp.6.1-6.10
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• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• Natural Product Sciences
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• 제8권1호
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

• International Journal of Computer Science & Network Security
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• 제21권12spc호
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• pp.526-538
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• 2021

Machine and deep learning-based models are emerging techniques that are being used to address prediction problems in biomedical data analysis. DNA sequence prediction is a critical problem that has attracted a great deal of attention in the biomedical domain. Machine and deep learning-based models have been shown to provide more accurate results when compared to conventional regression-based models. The prediction of the gene sequence that leads to cancerous diseases, such as prostate cancer, is crucial. Identifying the most important features in a gene sequence is a challenging task. Extracting the components of the gene sequence that can provide an insight into the types of mutation in the gene is of great importance as it will lead to effective drug design and the promotion of the new concept of personalised medicine. In this work, we extracted the exons in the prostate gene sequences that were used in the experiment. We built a Deep Neural Network (DNN) and Bi-directional Long-Short Term Memory (Bi-LSTM) model using a k-mer encoding for the DNA sequence and one-hot encoding for the class label. The models were evaluated using different classification metrics. Our experimental results show that DNN model prediction offers a training accuracy of 99 percent and validation accuracy of 96 percent. The bi-LSTM model also has a training accuracy of 95 percent and validation accuracy of 91 percent.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3971-3977
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• 2016

Background: Breast cancer, the commonest cancer among women in the world, ranks top in India with an incidence rate of 1,45,000 new cases and mortality rate of 70,000 women every year. Chemotherapy outcome for breast cancer is hampered due to poor response and irreversible dose-dependent cardiotoxicity which is determined by genetic variations in drug metabolizing enzymes and transporters. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, induces expression of drug metabolizing enzymes (DMEs) and transporters leading to regulation of xenobiotic metabolism. Materials and Methods: A genomic region spanning PXR 3' UTR was amplified and sequenced using genomic DNA isolated from 96 South Indian breast cancer patients. Genetic variants observed in our study subjects were queried in miRSNP to establish SNPs that alter miRNA binding sites in PXR 3' UTR. In addition, enrichment analysis was carried out to understand the network of miRNAs and PXR in drug metabolism using DIANA miRpath and miRwalk pathway prediction tools. Results: In this study, we identified SNPs rs3732359, rs3732360, rs1054190, rs1054191 and rs6438550 in the PXR 3; UTR region. The SNPs rs3732360, rs1054190 and rs1054191 were located in the binding site of miR-500a-3p, miR-532-3p and miR-374a-3p resulting in the altered PXR level due to the deregulation of post-transcriptional control and this leads to poor treatment response and toxicity. Conclusions: Genetic variants identified in PXR 3' UTR and their effects on PXR levels through post-transcriptional regulation provide a genetic basis for interindividual variability in treatment response and toxicity associated with chemotherapy.

• 대한화학회지
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• 제54권1호
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• pp.77-87
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• 2010

40여년전에 보고된 이래 병원에서 유래한 메치실린-저항 Staphylococcus aureus (MRSA) 은 세계적으로 큰 문제가 되어왔다. 항균성의 가능성을 가지는 새로운 약품을 개발하기 위하여 N'-[(-3-substituted-4-oxo-1,3-thiazolidin-2-ylidene]-4-hydroxy benzohydrazide (4a-4.i)와 N'-[-(3,4-disubstituted)-1,3-thiazolidin-2ylidene)]-4-hydroxybenzohydrazide (5.a-5.i)~(10.a-10.i)을 적절한 합성방법을 사용하여 합성하였다. 이들 합성된 화합물들은 s. aureus 균주에 대해 생체외 조건에서 분석하였다. 시료 화합물과 표준 화합물에 대해 최소억제농도(MIC)를 결정하였다. 시험한 모든 화합물들은 2000 ${\mu}g$/mL 투여량까지는 독성이 없었고, 사용한 균주에 대해 상당한 항균성을 보였다. 특히 6.f, 7.g, 9.f 와 10.f, 10 i 들이 가장 항균성이 컸다. 이것으로 미루어 파라-히드록시벤조히드라자이드 고리와 치환된 싸이아졸린 고리는 항균성에 필수적임을 알 수 있었다. 3D-QSAR 분석결과로 파라-히드록시벤조히드라자이드의 활성자리에 대한 결합방식을 알게되었다.

• Journal of Microbiology and Biotechnology
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• 제32권2호
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• pp.141-148
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• 2022

Many bone diseases such as osteolysis, osteomyelitis, and septic arthritis are caused by gram-negative bacterial infection, and lipopolysaccharide (LPS), a bacterial product, plays an essential role in this process. Drugs that inhibit LPS-induced osteoclastogenesis are urgently needed to prevent bone destruction in infective bone diseases. Marein, a major bioactive compound of Coreopsis tinctoria, possesses anti-oxidative, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic effects. In this study, we measured the effect of marein on RAW264.7 cells by CCK-8 assay and used TRAP staining to determine osteoclastogenesis. The levels of osteoclast-related genes and NF-κB-related proteins were then analyzed by western blot, and the levels of pro-inflammatory cytokines were quantified by ELISA. Our results showed that marein inhibited LPS-induced osteoclast formation by osteoclast precursor RAW264.7 cells. The effect of marein was related to its inhibitory function on expressions of pro-inflammatory cytokines and osteoclast-related genes containing RANK, TRAF6, MMP-9, CK, and CAII. Additionally, marein leads to markedly inhibited NF-κB signaling pathway activation in LPS-induced RAW264.7 cells. Concurrently, when the NF-κB signaling pathway was inhibited, osteoclast formation and pro-inflammatory cytokine expression were decreased. Collectively, marein could inhibit LPS-induced osteoclast formation in RAW264.7 cells via regulating the NF-κB signaling pathway. Our data demonstrate that marein might be a potential drug for bacteria-induced bone destruction disease. Our findings provide new insights into LPS-induced bone disease.

• 문화기술의 융합
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• 제8권3호
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• pp.405-413
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• 2022

COVID-19 이후 원격진료, 스마트 병원, AI 진단 등 ICT 기술과 데이터사이언스를 활용한 새로운 의료서비스모형의 활용이 크게 증가하고 있다. 본 연구에서는 최근 미국에서 원격진료와 대면진료의 혼합 모형 운영, 소비자 중심의 온라인의약품 배송, 가정용 진단기기 개발, 그리고 진료 및 처방, 의약품 배송, 진단기기의 활용이 통합적으로 제공되는 새로운 모형 제시 등 미국 헬스케어산업에서 파괴적 혁신을 선도하는 아마존의 헬스케어 사업 모형을 살펴보았다. 특히 아마존 기존 사업분야와의 시너지 효과 등으로 인해 적극적 시장 확대 및 소비자 가치 증대가 발생함을 다품목시장에서의 시장확대 모형을 통해 보였고, 또한 소비자 선택 유도 확대 시 의료서비스 시장에서의 경쟁이 활성화됨을 호텔링의 공간경쟁모형을 통해 보였다. 분석 결과 소비자 가치 증대의 장점과 함께 공급기반 감소에 따른 경쟁 약화의 부작용이 있을 수 있으므로 장기적으로 공정경쟁 관리 차원의 정책적 관심이 필요할 것으로 보인다.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2000년도 Proceedings of 2000 KSAM International Symposium and Spring Meeting
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• pp.3-6
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• 2000

Antimicrobial resistance has been a well-recognized problem ever since the introduction of penicillin into clinical use. History of antimicrobial development can be categorized based on the major antibiotics that had been developed against emerging resistant $pathogens^1$. In the first period from 1940 to 1960, penicillin was a dominating antibiotic called as a "magic bullet", although S.aureus armed with penicillinase led antimicrobial era to the second period in 1960s and 1970s. The second stage was characterized by broad-spectrum penicillins and early generation cephalosporins. During this period, nosocomial infections due to gram-negative bacilli became more prevalent, while those caused by S.aureus declined. A variety of new antimicrobial agents with distinct mechanism of action including new generation cephalosporins, monobactams, carbapenems, ${\beta}$-lactamase inhibitors, and quinolones characterized the third period from 1980s to 1990s. However, extensive use of wide variety of antibiotics in the community and hospitals has fueled the crisis in emerging antimicrobial resistance. Newly appeared drug-resistant Streptococcus pneumoniae (DRSP), vancomycin-resistant enterococci (VRE), extended-spectrum ${\beta}$-lactamase-producing Klebsiella, and VRSA have posed a serious threat in many parts of the world. Given the recent epidemiology of antimicrobial resistance and its clinical impact, there is no greater challenge related to emerging infections than the emergence of antibiotic resistance. Problems of antimicrobial resistance can be amplified by the fact that resistant clones or genes can spread within or between the species as well as to geographically distant areas which leads to a global concern$^2$. Antimicrobial resistance is primarily generated and promoted by increased use of antimicrobial agents. Unfortunately, as many as 50 % of prescriptions for antibiotics are reported to be inappropriate$^3$. Injudicious use of antibiotics even for viral upper respiratory infections is a universal phenomenon in every part of the world. The use of large quantities of antibiotics in the animal health industry and farming is another major factor contributing to selection of antibiotic resistance. In addition to these background factors, the tremendous increase in the immunocompromised hosts, popular use of invasive medical interventions, and increase in travel and mixing of human populations are contributing to the resurgence and spread of antimicrobial resistance$^4$. Antimicrobial resistance has critical impact on modem medicine both in clinical and economic aspect. Patients with previously treatable infections may have fatal outcome due to therapeutic failure that is unusual event no more. The potential economic impact of antimicrobial resistance is actually uncountable. With the increase in the problems of resistant organisms in the 21st century, however, additional health care costs for this problem must be enormously increasing.

• Bulletin of the Korean Chemical Society
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• 제31권1호
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• pp.52-58
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• 2010

Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.