• Journal of Pharmaceutical Investigation
• /
• 제39권1호
• /
• pp.1-6
• /
• 2009

To overcome the stability problem of hydrophilic quantum dot (Q-dot), cellular uptake of hydrophobic instead of hydrophilic Q-dot was studied in the hope to find a simple method to use Q-dot as a cellular imaging probe. Hydrophobic Q-dot and poly-L-lactic acid (PLLA) were co-dissolved in chloroform to prepare stable films. Due to the cellular compatibility of PLLA, adherent cells were cultured on the film to observe the degree of Q-dot uptake and cytotoxicity of the prepared films. The results show that Q-dots were absorbed into NIH3T3 and EMT6 cells. Cellular uptake was also observed when hydrophobic Q-dots were coated directly on a glass plate. PLLA/Q-dot film and Q-dot coated on glass plate did not show major cytotoxicity. In vivo tumor model was also used to show the uptake of Q-dot from the PLLA/Q-dot film to the tumor site.

• Journal of Information Processing Systems
• /
• 제12권4호
• /
• pp.724-740
• /
• 2016

The performance issues of screening large database compounds and multiple query compounds in virtual screening highlight a common concern in Chemoinformatics applications. This study investigates these problems by choosing group fusion as a pilot model and presents efficient parallel solutions in parallel platforms, specifically, the multi-core architecture of CPU and many-core architecture of graphical processing unit (GPU). A study of sequential group fusion and a proposed design of parallel CUDA group fusion are presented in this paper. The design involves solving two important stages of group fusion, namely, similarity search and fusion (MAX rule), while addressing embarrassingly parallel and parallel reduction models. The sequential, optimized sequential and parallel OpenMP of group fusion were implemented and evaluated. The outcome of the analysis from these three different design approaches influenced the design of parallel CUDA version in order to optimize and achieve high computation intensity. The proposed parallel CUDA performed better than sequential and parallel OpenMP in terms of both execution time and speedup. The parallel CUDA was 5-10x faster than sequential and parallel OpenMP as both similarity search and fusion MAX stages had been CUDA-optimized.

• Genomics & Informatics
• /
• 제16권3호
• /
• pp.44-51
• /
• 2018

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

• Journal of Pharmaceutical Investigation
• /
• 제38권6호
• /
• pp.429-432
• /
• 2008

Drug delivery systems (DDS) have entered mainstream in the pharmaceutical industry in the recent years. Major pharmaceutical companies as well as small or medium-sized biotechnology companies are developing various DDS-based products. We have established Drug Delivery System Company Database, which is an online searchable database of companies that develop DDS-based products and technologies or supply formulations and/or materials. Company summary, products and key technologies are listed in the database. DDS technology fields also include administration routes and indications of drugs. DDS terminologies, Statistical analysis, Useful Links, Glossary and Comments pages are also provided.

• Biomolecules & Therapeutics
• /
• 제17권3호
• /
• pp.311-317
• /
• 2009

Ginkgo biloba (G. biloba) extract is a widely used phytomedicine for the oral treatment of peripheral vascular disease. Cilostazol is a synthetic antiplatelet and vasodilating agent for the treatment of intermittent claudication resulting from peripheral arterial disease. It is likely to use concomitantly G. biloba extract and cilostazol for the treatment of peripheral arterial disease, which raises a concern of increasing their adverse effects of herbal-drug interactions. To clarify any possible herbal-drug interaction between G. biloba extract and cilostazol, the effect of the G. biloba extract on the pharmacokinetics of cilostazol was investigated. As cilostazol is known to be eliminated mainly by cytochrome P450 (CYP)-mediated metabolism, we investigated the effects of G. biloba extract on the human CYP enzyme activities and the effect of G. biloba extract on the pharmacokinetics of cilostazol after co-administration of the two agents to male beagle dogs. The G. biloba extract inhibited more or less CYP2C8, CYP2C9, and CYP2C19 enzyme activities in the in vitro microsomal study with $IC_{50}$ values of 30.8, 60.5, and $25.2{\mu}g/ml$, respectively. In the pharmacokinetic study, co-administration with the G. biloba extract had no significant effect on the pharmacokinetics of cilostazol in dogs, although CYP2C has been reported to be responsible for the metabolism of cilostazol. In conclusion, these results suggest that there may not be a pharmacokinetic interaction between G. biloba extract and cilostazol.

• Toxicological Research
• /
• 제35권4호
• /
• pp.295-301
• /
• 2019

In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = -0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = -0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.

• 한국생물정보학회:학술대회논문집
• /
• 한국생물정보시스템생물학회 2001년도 제2회 생물정보학 국제심포지엄
• /
• pp.129-137
• /
• 2001

We used cDNA microarrays to assess gene expression profiles in 60 human cancer used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity pattens in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to intergrate large databases on gene expression and molecular pharmacology.