• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2020년도 추계국제학술대회
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• pp.14-14
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• 2020

In December 2019, the COVID-19 epidemic was discovered in Wuhan, China, and since has disseminated around the world impacting human health for millions. Herein, in-silico drug discovery approaches were utilized to identify potential candidates as Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro) inhibitors. We investigated several databases including natural and natural-like products (>100,000 molecules), DrugBank database (10,036 drugs), major metabolites isolated from daily used spices (32 molecules), and current clinical drug candidates for the treatment of COVID-19 (18 drugs). All tested compounds were prepared and screened using molecular docking techniques. Based on the calculated docking scores, the top ones from each project under investigation were selected and subjected to molecular dynamics (MD) simulations followed by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. Combined long MD simulations and MM-GBSA calculations revealed the potent compounds with prospective binding affinities against M^pro. Structural and energetic analyses over the simulated time demonstrated the high stabilities of the selected compounds. Our results showed that 4-bis([1,3]dioxolo)pyran-5-carboxamide derivatives (natural and natural-like products database), DB02388 and Cobicistat (DB09065) (DrugBank database), salvianolic acid A (spices secondary metabolites) and TMC-310911 (clinical-trial drugs database) exhibited high binding affinities with SARS-CoV-2 M^pro. In conclusion, these compounds are up-and-coming anti-COVID-19 drug candidates that warrant further detailed in vitro and in vivo experimental estimations.

• Bulletin of the Korean Chemical Society
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• 제29권4호
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• pp.833-841
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• 2008

Principal component-genetic algorithm-multiparameter linear regression (PC-GA-MLR) and principal component-genetic algorithm-artificial neural network (PC-GA-ANN) models were applied for prediction of melting point for 323 drug-like compounds. A large number of theoretical descriptors were calculated for each compound. The first 234 principal components (PC’s) were found to explain more than 99.9% of variances in the original data matrix. From the pool of these PC’s, the genetic algorithm was employed for selection of the best set of extracted PC’s for PC-MLR and PC-ANN models. The models were generated using fifteen PC’s as variables. For evaluation of the predictive power of the models, melting points of 64 compounds in the prediction set were calculated. Root-mean square errors (RMSE) for PC-GA-MLR and PC-GA-ANN models are 48.18 and $12.77{^{\circ}C}$, respectively. Comparison of the results obtained by the models reveals superiority of the PC-GA-ANN relative to the PC-GA-MLR and the recently proposed models (RMSE = $40.7{^{\circ}C}$). The improvements are due to the fact that the melting point of the compounds demonstrates non-linear correlations with the principal components.

• Genomics & Informatics
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• 제14권4호
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• pp.241-254
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• 2016

Environmental microbes like Bordetella petrii has been established as a causative agent for various infectious diseases in human. Again, development of drug resistance in B. petrii challenged to combat against the infection. Identification of potential drug target and proposing a novel lead compound against the pathogen has a great aid and value. In this study, bioinformatics tools and technology have been applied to suggest a potential drug target by screening the proteome information of B. petrii DSM 12804 (accession No. PRJNA28135) from genome database of National Centre for Biotechnology information. In this regards, the inhibitory effect of nine natural compounds like ajoene (Allium sativum), allicin (A. sativum), cinnamaldehyde (Cinnamomum cassia), curcumin (Curcuma longa), gallotannin (active component of green tea and red wine), isoorientin (Anthopterus wardii), isovitexin (A. wardii), neral (Melissa officinalis), and vitexin (A. wardii) have been acknowledged with anti-bacterial properties and hence tested against identified drug target of B. petrii by implicating computational approach. The in silico studies revealed the hypothesis that lpxD could be a potential drug target and with recommendation of a strong inhibitory effect of selected natural compounds against infection caused due to B. petrii, would be further validated through in vitro experiments.

• 셀메드
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• 제6권4호
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• pp.22.1-22.19
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• 2016

The biologically active compounds derived from different natural organisms such as animals, plants, and microorganisms like algae, fungi, bacteria and merine organisms. These natural compounds possess diverse biological activities like anthelmintic, antibacterial, antifungal, antimalarial, antiprotozoal, antituberculosis, and antiviral activities. These biological active compounds were acted by variety of molecular targets and thus may potentially contribute to several pharmacological classes. The synthesis of natural products and their analogues provides effect of structural modifications on the parent compounds which may be useful in the discovery of potential new drug molecules with different biological activities. Natural organisms have developed complex chemical defense systems by repelling or killing predators, such as insects, microorganisms, animals etc. These defense systems have the ability to produce large numbers of diverse compounds which can be used as new drugs. Thus, research on natural products for novel therapeutic agents with broad spectrum activities and will continue to provide important new drug molecules.

• 환경위생공학
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• 제22권3호
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• pp.89-96
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• 2007

To determine 8 anti-impotence drug/drug-like compounds such as sildenafil, vardenafil, tadalafil, homosildenafil, hydroxyhomosildenafil, aminotadalafil, pseudovardenafil and hongdenafil in foods, simultaneously, high performance liquid chromatography(HPLC) and liquid chromatography-mass spectrometry (LC/MS) were used. The HPLC/UV analysis was performed on a column of capcellpak $C_{18}$ with 0.1% sodium-1-hexansulfonate in 0.2M ammonium formate/acetonitrile as a mobile phase. Mass spectra of the compounds by LC/MS were investigated with SCAN mode(Mass range and Fragment voltage) and SIM(Selected Ion Monitoring) mode (Ion target and Fragment voltage). The results follow as; 1. The HPLC/UV analysis was detected from 5 out of 63 samples. The content of sildenafil was in the range of 32.80 ppm ${\sim}$ 60.13 ppm from 4 out of 5 samples. The contents of sildenafil, vardenafil, homosildenafil were in the range 47.14 ppm from 1 out of 5 samples. 2. The conformed result of LC/MS was equal of detected from 5 out of 63 samples in HPLC/UV analysis. An easily available, simultaneous determination of 8 standards in adulterated health related foods was established by using a combination of LC/MS methods.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2291-2295
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• 2016

Small molecule tyrosine kinase inhibitors targeting HER 2 receptors have emerged as an important therapeutic approach in inhibition of downstream proliferation and survival signals for the treatment of breast cancers. Recent drug discovery efforts have demonstrated that naturally occurring polyphenolic compounds like delphinidin have potential to inhibit proliferation and promote apoptosis of breast cancer cells by targeting HER2 receptors. While delphinidin may thus reduce tumour size, it is associated with serious side effects like dysphonia. Owing to the narrow therapeutic window of delphinidin, the present study aimed to identify high affinity compounds targeting HER2 with safer pharmacological profiles than delphinidin through virtual screening approaches. Delphinidin served as the query parent for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. The compounds retrieved were further subjected to Lipinski and Verber's filters to obtain drug like agents, then further filtered by diversity based screens with a cut off of 0.6. The compound with Pubchem ID: 91596862 was identified to have higher affinity than its parent. In addition it also proved to be non-toxic with a better ADMET profile and higher kinase activity. The compound identified in the study can be put to further in vitro drug testing to complement the present study.

• 분석과학
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• 제20권1호
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• pp.78-83
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• 2007

식품 중 발기부전치료 성분 및 유사물질의 분석능력을 평가하기 위하여 실험실간 정도관리를 시도하였다. 평가대상물질은 실데나필, 타다라필, 바데나필, 호모실데나필, 하이드록시호모실데나필, 슈도바데나필 6종이었으며, 참여기관은 식품위생검사를 담당하고 있는 13개 기관이었다. 표준시료는 이중맹검을 위하여 평가대상물질 중 임의의 3종을 함유하도록 조제한 인삼음료 13개이었다. 분석방법은 식품공전의 일반시험법에 제시되어 있는 발기부전치료제 유사물질 시험법에 따라 일정량을 취하여 물에 희석한 후 유기용매로 추출하여 HPLC/UV로 분석하고 LC/MS로 확인하는 방법을 적용하였다. 분석기간은 표준시료를 수령한 날로부터 60일이었다. 검사능력관리규정에 따라 Z-값 및 RSZ를 종합평가한 결과 10기관이 만족한 수준이었다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.90-90
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• 2003

I describe here a novel and promising approach to drug discovery that involves the identification and assembly of drug-like fragments to afford lead compounds. This approach is attractive for a number of reasons. First, the productive assembly of two weakly bound fragments, even fragments with independent dissociation constants in the low mM range, can potentially afford ligands with sub-micromolar affinities for their targets. (omitted)

• 분석과학
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• 제17권6호
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• pp.520-526
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• 2004

식품 중 발기부전치료제 및 유사물질 (anti-impotence drug-like compounds)인 실데나필, 바데나필, 타다라필, 호모실데나필, 홍데나필 및 하이드록시호모실데나필에 대해 고속액체크로마토그라피를 이용하여 동시분석을 시도하였다. 환제나 캅슐제 등 고체 시료의 경우 균질화한 후 일정량을 취하고, 드링크제 등 액체시료의 경우 일정량을 취하여 물에 희석한 후 유기용매로 추출하여 대상물질에 대해 photodiode array 스펙트럼의 최대흡수파장을 확인하였다. 인산을 함유한 아세토니트릴을 이동상으로 하고 $C_{18}$ 컬럼으로 분석한 결과 바데나필, 홍데나필, 하이드록시호모실데나필, 실데나필, 호모실데나필, 타다라필의 순으로 용리되었으며, PDA 스펙트럼의 최대흡수파장은 바데나필의 경우 216 nm, 홍데나필의 경우 233 및 282 nm, 하이드록시호모실데나필, 실데나필 및 호모실데나필의 경우 222 및 293 nm, 그리고 타다라필의 경우 284 nm이었다. 검출한계는 물질마다 차이는 있으나 신호대 잡음비 3이상에서 0.04 mg/kg이었으며 평균 회수율은 95 ~ 109% 이었고 식품시료 중 검출된 대상물질은 1.7 (홍데나필) ~ 63 (타다라필) mg/1회복용량 수준이었다.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3760-3764
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• 2010

We screened 10,000 heterocyclic small molecules and identified a novel hit core skeleton of 3-(8-chloro-6-(trifluoromethyl) imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives. It has been selected as a potential glucagon-like peptide 1 receptor (GLP-1R) activator and demonstrated its effects in increasing GLP-1 secretion, and thereby increasing the glucose responsiveness in both in vitro and pharmacology analyses. Further studies are currently underway to optimize the potency and selectivity of 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate derivatives (hit compounds 2 and 8), and address their in vivo efficacy and therapeutic potential. These molecules may serve as useful evidence showing that compounds with a 3-(8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-yl)phenyl acetate moiety are selective GLP-1R agonists, and have potential as anti-diabetic treatment agents.