• Bulletin of the Korean Chemical Society
• /
• 제35권7호
• /
• pp.2065-2071
• /
• 2014

${\beta}$-Secretase (beta-amyloid converting enzyme 1 [BACE1]) is involved in the first and rate-limiting step of ${\beta}$-amyloid ($A{\beta}$) peptides production, which leads to the pathogenesis of Alzheimer's disease(AD). Therefore, inhibition of BACE1 activity has become an efficient approach for the treatment of AD. Ligand-based and docking-based 3D-quantitative structure-activity relationship (3D-QSAR) studies of acyl guanidine analogues were performed with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to obtain insights for designing novel potent BACE1 inhibitors. We obtained highly reliable and predictive CoMSIA models with a cross-validated $q^2$ value of 0.725 and a predictive coefficient $r{^2}_{pred}$ value of 0.956. CoMSIA contour maps showed the structural requirements for potent activity. 3D-QSAR analysis suggested that an acyl guanidine and an amide group in the $R_6$ substituent would be important moieties for potent activity. Moreover, the introduction of small hydrophobic groups in the phenyl ring and hydrogen bond donor groups in 3,5-dichlorophenyl ring could increase biological activity.

• 통합자연과학논문집
• /
• 제15권4호
• /
• pp.145-152
• /
• 2022

Colon rectal cancer is one of the frequently diagnosed cancers worldwide. In recent times the drug discovery for colon cancer is challenging because of their speedy metastasis and morality of these patients. C-jun N-terminal kinase signaling pathway controls the cell cycle survival and apoptosis. Evidence has shown that JNK1 promotes the tumor progression in various types of cancers like colon cancer, breast cancer and lung cancer. Recent study has shown that inhibiting, JNK1 pathway is identified as one of the important cascades in drug discovery. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened ChEMBL dataset against JNK1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top compounds to be more specific with JNK1 comparing the affinity with JNK2 and JNK3.The drugs which exhibited higher binding were subjected to Conceptual - Density functional theory. The results showed mainly Entrectinib and Exatecan showed better binding to the target.

• 통합자연과학논문집
• /
• 제10권2호
• /
• pp.74-77
• /
• 2017

Bradykinin receptor B2 (B2R) is a GPCR protein which binds with the inflammatory mediator hormone bradkynin. Kallidin, a decapeptide, also signals through this receptor. B2R is crucial in the cross-talk between renin-angiotensin system (RAS) and the kinin-kallikrein system (KKS) and in many processes including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Thus the structural study of the receptor becomes important. We have predicted the peptide structures of Bradykinin and Kallidin from their amino acid sequences and the structures were docked with the receptor structure. The results obtained from protein-protein docking could be helpful in studying the B2R structural features and in the pathophysiology in various diseases related to it.

• 통합자연과학논문집
• /
• 제16권3호
• /
• pp.81-95
• /
• 2023

Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

• 통합자연과학논문집
• /
• 제16권4호
• /
• pp.123-131
• /
• 2023

Breast cancer continues to pose a substantial worldwide health challenge, thereby requiring the development of innovative strategies to discover new therapeutic interventions. Signal Transducer and Activator of Transcription 3 (STAT-3) has been identified as a significant factor in the development of several types of cancer, including breast cancer. This is primarily attributed to its diverse functions in promoting tumour formation and conferring resistance to therapeutic interventions. This study presents an in silico drug repositioning approach that focuses on identifying specific inhibitors of STAT-3 for the purpose of treating breast cancer. We initially examined the structural and functional attributes of STAT-3, thereby elucidating its crucial involvement in cellular signalling cascades. A comprehensive virtual screening was performed on a diverse collection of drugs that have been approved by the FDA from zinc15 database. Various computational techniques, including molecular docking, cross docking, and cDFT analysis, were utilised in order to prioritise potential candidates. This prioritisation was based on their predicted binding energies and outer molecular orbital reactivity. The findings of our study have unveiled a Dihydroergotamine and Paritaprevir that have been approved by the FDA and exhibit considerable promise as selective inhibitors of STAT-3. In conclusion, the utilisation of our in silico drug repositioning approach presents a prompt and economically efficient method for the identification of potential compounds that warrant subsequent experimental validation as selective STAT-3 inhibitors in the context of breast cancer. The present study highlights the considerable potential of employing computational strategies to expedite the drug discovery process. Moreover, it provides valuable insights into novel avenues for targeted therapeutic interventions in the context of breast cancer treatment.

• Journal of Microbiology and Biotechnology
• /
• 제27권3호
• /
• pp.542-551
• /
• 2017

Small phytochemicals have been successfully adopted as antibacterial chemotherapies and are being increasingly viewed as potential antibiofilm agents. Some of these molecules are known to repress biofilm and toxin production by certain bacterial and yeast pathogens, but information is lacking with regard to the genes allied with biofilm formation. The present study was performed to investigate the inhibitory effect of burdock root extract (BRE) and of chlorogenic acid (CGA; a component of BRE) on clinical isolates of Klebsiella pneumoniae. BRE and CGA exhibited significant antibiofilm activity against K. pneumoniae without inflicting any harm to its planktonic counterparts. In vitro assays supported the ${\beta}$-lactamase inhibitory effect of CGA and BRE while in silico docking showed that CGA bound strongly with the active sites of sulfhydryl-variable-1 ${\beta}$-lactamase. Furthermore, the mRNA transcript levels of two biofilm-associated genes (type 3 fimbriae mrkD and trehalose-6-phosphate hydrolase treC) were significantly downregulated in CGA- and BRE-treated samples. In addition, CGA inhibited biofilm formation by Escherichia coli and Candida albicans without affecting their planktonic cell growth. These findings show that BRE and its component CGA have potential use in antibiofilm strategies against persistent K. pneumoniae infections.

• 한국해양공학회:학술대회논문집
• /
• 한국해양공학회 2004년도 학술대회지
• /
• pp.249-256
• /
• 2004

KRISO/KORDI is currently developing a deep-sea unmanned underwater vehicle (UUV) system which is composed of a launcher, an ROV, and an AUV. Two USBL acoustic positioning systems will be used for UUV's navigation. One is for the deep sea positioning of all three vehicles and the other is for AUV's guidance to the docking device on the launcher. In order to increase the position accuracy MFSK(Multiple Frequency Shift Keying) broadband signal will be used. As the first step to the implementation of a USBL system, this paper studies USBL positioning algorithm using MFSK signals. Firstly, the characteristics of MFSK signal is described with various MFSK parameters: number of frequencies, frequency step, center frequency, and pulse length. Time and phase delays between two received signals are estimated by using cross-correlation and cross-spectrum methods. Finally an USBL positioning algorithm is derived by converting the delays to difference of distances and applying trigonometry. The simulation results show that the position accuracy is improved highly when both cross-correlation and cross-spectrum of MFSK signals are used simultaneously.

• 대한화학회지
• /
• 제56권2호
• /
• pp.236-245
• /
• 2012

The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.

• 경영과학
• /
• 제34권1호
• /
• pp.1-13
• /
• 2017

The percentage of 3PL (Third-party Logistics), which uses third party businesses to outsource elements of the company's distribution and fulfillment services, is increasing steadily. To provide 3PL service to the customers, it is needed to estimate the total transportation cost and propose the unit cost to the customers. In this paper, we develop a decision support system for estimation of transportation cost of 3PL provider considering various transportation services, such as direct transportation, multi point visiting transportation, and cross docking. The system supports route planning of vehicles by using algorithms based on tabu search and dynamic programming.

• 한국국방경영분석학회지
• /
• 제32권2호
• /
• pp.40-55
• /
• 2006

본 연구논문에서는 공군 군수지원체계에 대한 SCM 도입방안 제시를 목적으로 한다. 이것을 제시하기에 앞서 이해를 돕기 위해 SCM의 개념과 관련기법들을 살펴보고, SCM을 바탕으로 군수개혁에 성공한 미국의 사례를 분석하였다. 공군 군수지원체계 중에서 중요하다고 판단되는 항공기 수리부속에 대한 수송체계와 보급정보체계 측면에서 SCM 도입방안을 제시하였다. 공군은 첨단정보통신기술을 기반으로 하며, 저비용, 고효율의 혁신적인 군수지원체계를 구축함으로써 완벽한 임무지원능력을 배양할 수 있게 될 것이다.