• Biomolecules & Therapeutics
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• 제32권4호
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• pp.442-450
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• 2024

The type-1 cannabinoid receptor (CB₁R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB₁R ligands. In this study, CB₁R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB₁R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB₁R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB₁R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB₁R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB₁R, which can be used to control psychiatric disorders and drug abuse.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.29-38
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• 2023

Recent studies have highlighted the link between diseases and inflammation across our lifespan. Our sedentary lifestyle, high-calorie diet, chronic stress, chronic infections, and exposure to pollutants and xenobiotics, collectively intensify the course and recurrence of infections and inflammation in our bodies, promoting the prevalence of chronic diseases and aging. Given such phenomena and considering additional factors such as the frequency of prescription, and easy access to over-the-counter drugs, the need for anti-inflammatory therapeutics is ever-increasing. However, the readily available anti-inflammatory treatment option comes with a greater risk of side effects or high cost (biologics). Therefore in this growing competition of discovering and developing new potent anti-inflammatory drugs, we focused on utilizing the established knowledge of traditional medicine to find lead compounds. Since lead optimization is an indispensable step toward drug development, we applied this concept for the production of potent anti-inflammatory compounds achieved by structural modification of flavonoids. The derivative obtained through acetylation of myricetin, 3,3',4',5,5',7-hexaacetate myricetin, showed a greater inhibitory effect in the production of pro-inflammatory mediators such as nitric oxide, Prostaglandin E₂, and pro-inflammatory cytokines like interleukin-6, interleukin1β, in lipopolysaccharide-stimulated RAW264.7 mouse macrophage cells compared to myricetin. The increased potency of inhibition was in conjunction with an increased inhibitory effect on inducible nitric oxide synthase and cyclooxygenase-2 proteins. Through such measures, this study supports lead optimization for well-established lead compounds from traditional medicine using a simpler and greener chemistry approach for the purpose of designing and developing potent anti-inflammatory therapeutics with possibly fewer side effects and increased bioavailability.

• 응용통계연구
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• 제26권4호
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• pp.675-686
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• 2013

현재 우리나라 식품의약품안전청에서는 $2{\times}2$ 교차설계법을 기초로 제제간의 생물학적 동등성 평가를 수행하도록 규정하고 있다. 하지만 고변동성 제제의 생물학적 동등성 평가에서 $2{\times}2$ 교차설계법에 의한 시험은 지나치게 많은 피험자를 필요로 할 수 있어 윤리적이고 경제적인 고려가 필요하다는 논의가 이루어지고 있다. $2{\times}2$ 교차설계법을 대체할 수 있는 대안으로 $2{\times}4$ 교차설계법은 미국 및 유럽 등에서는 생물학적 동등성 평가에 광범위하게 사용되는 설계 방법이고, $2{\times}3$ 교차설계법도 $2{\times}2$와 $2{\times}4$ 교차설계법의 단점을 개선할 수 있는 효율적인 대안으로 관심이 많다. 본 연구에서는 $2{\times}4$와 $2{\times}3$ 교차설계법의 통계적 모형과 제시된 통계적 모형에 연계된 분산분석표를 유도한다. 현행 국내 생물학적 동등성 시험 규정에 의하면 $2{\times}4$와 $2{\times}3$ 교차설계법의 분산분석표는 반드시 제시되어야 하지만 아직 문헌상에 존재하지 않아 관련 연구에 기여할 것으로 생각된다. 또한 $2{\times}4$와 $2{\times}3$ 교차설계법에 기초한 피험자 계산을 $2{\times}2$ 교차설계법과 비교 제시하여 고변동성 제제의 생물학적 동등성 시험 연구에 적절한 시험 설계 선택에 정보를 제공한다.

• 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.

• 농촌의학ㆍ지역보건
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• 제13권1호
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• pp.3-18
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• 1988

The general objective of this research is to study behavioral pattern of health care utilization and to measure the level of utilization of the traditional medicine. The specific objective is to study utilization pattern and content of folk medicine which is the indegenous medical technology recognized part of traditional medicine. This research was under taken to generate valid information that will provide basis data for formulating general direction for health education activities and for designing service package for general population. A social survey method was employed to obtain required information for the research activities, The survey field team consisted of 20 surveyors who all participated is an intensive 2 day training course. A total of 3091 households were visited and interviewed by the field team during the period 7 September to 6 October 1987. The major findings obtained from the information collected by the field survey are as follows ; 1) General characteristics of the study households 2562 households out of 3091 households visited were selected for final data process, 80.2 of the selected households were nuclear families ; 17.4%, extended families ; others 2.4%. Only 4.3 percent of the study population in the urban households indicated "no schooling" whereas 14.2% of the rural household members falls within this category. Study population in the urban areas are more protected against diseases by the national medical insurance system than those in rural areas. In their self appraisal of living standard, those who responded with low group are 39.6% and 50.3% respectively by urban and rural households. 2) Morbidity status Period prevalence rate for all diseases during the preceding 15 days before the date of the household interview v as 243,0 per 1,000 study population. For cases with the illness duration of within 15 days, the initial points of medical entry were diversied ; 56.9%, drug stores ; 30.9%, clinics and hospitals ; 4.6% folk medicine ; 1.7% clinics of Korean oriental medicine. Among the chronic case; with illness duration of over 90 days, 34.6% of these people utilized clinics and hospitals of modern medicine ; 31.6%, drug stores ; 18.6% clinics of Korean oriental medicine ; 6.8% folk medical techniques. Noticeable is the almost ten fold increase from the mere 0.9% in the utilization of Korean oriental medicine, whereas in the utilization of folk medicine, it is short of two-fold increase. 3) Folk medicine and its utilization Households that use folk medicine for relief and care of signs and symptoms commonly encountered in daily life, number 1969 households, which accounts for 76.9% of all the study households. This rather high level use of folk medicine is not different from rural to urban areas. The order of frequency of utilizing folk medicine among the study people are : the highest 14.3% for the relief of indigestion ; 8.6% for burns ; 5.1% for common cold ; 4.7% for hiccough ; and 4.2% for hordeolum. A present various procedures of folk medicine is being used to relieve all kinds of symptoms. 192 symptoms are identified at present. The most frequently used procedures of folk medicine appear to be based either on principles of the Korean oriental medicine or of scientific knowledge. Based on these survey findings, proposals for utilizing folk medicine are as follows First, this survey's findings will be feed back to both on the job training and on the spot guidance of community health practitioners, public health nurses and other peripheral work force in the health field, who are in daily contacts with community. This feed back will assure that the health personnel carry out their health education and information activities that are based on the utilization pattern of folk medicine as found in the survey result. Second, studies will be soon implemented that are designed to measure the efficiency and potency of these procedures and to improve these procedures of folk medicine were most frequently used by the community. Third, studies will continue to systematize medicinal plants and skills of Korean oriental medicine that are easily available at minimal cost in daily life for the prevention of diseases and management of emergency cases.