• Archives of Pharmacal Research
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• 제26권12호
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• pp.985-989
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• 2003

An efficient synthesis of 5-chloro-3-[4-(3-diethylaminopropoxy)benzoyl]-2-(4-methoxyphenyl)benzofuran (8), a potent $\beta$-amyloid aggregation inhibitor, is described. 5-Chloro-2-(4-methoxyphenyl)benzofuran (3) was obtained by the one-pot synthesis of 4-chlorophenol with $\omega$(methylsulfinyl)-p-methoxyacetophenone (1) under Pummerer reaction conditions, and it was followed by the desulfurization of the resultant 5-chloro-3-methylthio-2-(4-methoxyphenyl)benzofuran (2e). Acylation of benzofuran 3 with 4-(3-bromopropoxy)benzoyl chloride (6) gave the ketone 7, which was converted into compound 8 by the treatment of diethylamine.

• Natural Product Sciences
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• 제10권6호
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• pp.315-320
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• 2004

Alpha-viniferin was previously isolated as a cyclooxygenase (COX)-2 inhibitor from Carex humilis (Cyperaceae) and is an oligomeric stilbene compound with benzofuran (BF) moieties in its chemical structure. In the present study, a chemically synthetic BF compound, named as 3,3-dimethyl-2,3,4,6,7,8,9,10,11,12,13,14,15,16,17,18-hexadecahydro-1H-benzo[b] cyclopentadeca[d]furan-1-one, was discovered to inhibit bacterial lipo polysaccharide (LPS)-induced prostaglandin $E_2$ $(PGE_2)$ production in macrophages RAW 264.7. The BF compound exhibited a selectively preferred inhibitory effect on COX-2 activity over COX-1 activity. Furthermore, BF compound inhibited LPS-induced COX-2 expression at transcription level. As a down-regulatory mechanism of COX-2 expression shown by BF compound, suppression of nuclear factor $(NF)-{\kappa}B$ activation has been demonstrated. BF compound inhibited LPS-induced $NF-{\kappa}B$ transcriptional activity and nuclear translocation of $NF-{\kappa}B$ p65, in parallel, but did not affect LPS-induced degradation of inhibitory ${\kappa}B{\alpha}$ protein $(I{\kappa}B{\alpha})$. Taken together, anti-inflammatory effect of BF compound on $PGE_2$ production was ascribed by its down-regulatory action on LPS-induced COX-2 synthesis in addition to inhibitory action on enzyme activity of COX-2.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.826-833
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• 2006

Previously, we synthesized and evaluated several benzofuran derivatives containing heterocyclic ring substituents linked to the benzofuran nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1, anticancer and antimicrobial agents. Among these derivatives, NSC 725612 and NSC 725716 exhibited interesting anti-HIV-1 activity. To further investigate the structure-activity relationship, we synthesized several new benzofuran derivatives derived from 2-acetylbenzofuran (2, 3a-c) and 2-bromoacetylbenzofuran (6; 7a,b; 8a,b). The compounds were designed to comprise the heterocyclic substituents directly linked to the benzofuran nucleus at C-2. Moreover, various related benzimidazoles derived from 2-acetylbenzimidazole and from 2-cyanomethylbenzimidazole (12a,b; 13a,b; 15; 16a,b) were also prepared as isosteres. The synthesized compounds were preliminarily evaluated for their in vitro anti-HIV-1, anticancer and antimicrobial activity. Compounds 2, 3a, 3b, and 12b showed weak anti-HIV-1 activity. Compound 6 exhibited mild activity against S. aureus, while compound 15 had mild activity towards S. aureus and C. albicans. However, no significant anticancer activity was observed with any of the tested compounds. From these results, we conclude that the presence of the spacer between the heterocyclic substituent and the benzofuran nucleus may be essential for the biological activity.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.275-282
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• 2015

In the present study, we synthesized a series of novel 7-methoxy-N-(substituted phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and evaluated their neuroprotective and antioxidant activities using primary cultured rat cortical neuronal cells and in vitro cell-free bioassays. Based on our primary screening data with eighteen synthesized derivatives, nine compounds (1a, 1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the NMDA-induced excitotoxic neuronal cell damage at the concentration of $100{\mu}M$ were selected for further evaluation. Among the selected derivatives, compound 1f (with $-CH_3$ substitution at R2 position) exhibited the most potent and efficacious neuroprotective action against the NMDA-induced excitotoxicity. Its neuroprotective effect was almost comparable to that of memantine, a well-known NMDA antagonist, at $30{\mu}M$ concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and $300{\mu}M$ concentrations. These findings suggest that $-CH_3$ substitution at R2 position and, to a lesser degree, -OH substitution at R3 position may be important for exhibiting neuroprotective action against excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain homogenate in moderate and appreciable degrees. Taken together, our structure-activity relationship studies suggest that the compound with $-CH_3$ substitution at R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant activities. Further synthesis and evaluation will be necessary to confirm this possibility.

• Archives of Pharmacal Research
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• 제29권1호
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• pp.16-25
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• 2006

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles(3a-c, 4a-f) and thiazolidin-4-ones(5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide(7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones(8a-c); 2-thioxo-2,3-dihydro-thiazoles(9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction ㅐ ㄹ the viral cytopathic effect (93.19% and 59.55%) at concentrations $>2.0{\times}10^{-4}\;M\;and\;2.5{\times}10^{-5}\;M$respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.

• 대한화학회지
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• 제44권4호
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• pp.343-349
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• 2000

PC/Monitor의 구성 전자부품으로부터 방출되는 휘발성 유기화합물(Volatile Organic Com-pounds,VOCs)를 분석하였다. Mpnitor를 구성하는 전자부품으로부터 연속으로 방출되는 VOCs의 경향을 시료챔버에 직접 연결되어있는 잔류가스 분석기(Residual Gas Analyzer,RG A)로 분석하였으며, 이들 전자부품에서 방출되는 VOCs의 성분을 RGA와 GC-MS로 분석하였다. 정성분석된 VOCs 중 소량으로 방출되거라도 불쾌한냄새와 건강상의 장해를 초래할 수 있는 toluene. xylene, cyclohexanone 및 benzofuran에 대하여 GC-MS로 정량분석하였다. 이러한 분석결과, 전자부품중 PCB(CEM-1)을제외하고 나머지 부품들은 가열시작 후 30분에서 1시간동안 toluene, xylene, cyclohexanone 및 phenol이 다량으로 연속 방출되는 경향을 나타내었으며, 거의 모든 전자부품에서 toluene, xylene, phenol, cyclohexanone 및 benzofuran 등의 물질들이측정시간 범위내에서 가장 빈번하게 방출되었다. 부품들 중 Trans가 가장 높은 VOCs의 방출농도를 보였으며, 전자부품으로부터 정량분석된 VOCs중에는 xylene의 방출농도가 550~2482 ${\mu}g/m^2$로 가장 크게 나타났다.

• Journal of Applied Biological Chemistry
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• 제58권4호
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• pp.295-301
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• 2015

Five phenylpropanoids (1-5), a benzofuran neolignan (6), two 8-O-4'-neolignans (7-8), and five tetrahydrofuran lignans (9-13) were isolated from a methanol extract of Myristica fragrans seeds. The structures of 1-13 were determined by $^1H$- and $^{13}C$-NMR spectroscopic data analyses and a comparison with the literature data. Compound 3 was isolated for the first time from this plant. All the isolated compounds were evaluated for their inhibitory activity against tyrosinase. Among them, safrole (1) showed significant inhibitions against both the monophenolase ($IC_{50}=32.11{\mu}M$) and diphenolase ($IC_{50}=27.32{\mu}M$) activities of tyrosinase. The kinetic analysis shows that safrole (1) is competitive inhibitors for both monophenolase and diphenolase. The apparent inhibition constant ($K_i$) for safrole (1) binding with free enzyme was determined to be 16.05 and $13.66{\mu}M$ for monophenolase and diphenolase, respectively.

• 한국식품조리과학회지
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• 제17권6호
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• pp.565-570
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• 2001

본 연구에서는 쇠비름을 메탄올로 추출하여 식품의 부패나 식중독성을 유발하는 세균과 곰팡이에 대한 추출물의 항균활성을 검토하고 그들의 최소생육저해농도를 결정하였으며 쇠비름 추출물의 구성성분과 함량을 분석하였다. 쇠비름은 특히 P. citreonigrum 균주에 대해 매우 높은 항균효과를 보였고 S aureus, K. pneumoniae에 대해서는 benzoic acid에 상응할 만한 항균효과를 나타내었다. 쇠비름 메탄올 추출물은 200mg/$m\ell$ 농도에서 S. aureus와 P. citreonigrum의 생육을 억제하였고, 250 mg/$m\ell$ 농도에서 K. pneumoniae의 생육을 억제하였으며, 300 mg/$m\ell$ 농도에서 P. aeruginosa와 E. coli의 생육을 억제하였다. 따라서 이들 균주에 의한 식품의 부패 및 식중독이 우려되는 식품의 항균제로서 쇠비름의 사용 가능성을 볼 수 있었다. 쇠비름 메탄올 추출물의 분석결과 전체 147가지 성분이 분석되었으며 acid 및 ester류가 41.06%로 추출물의 가장 많은 부분을 차지하고 있었다. 또한 세균, 곰팡이, 효모와 같은 미생물에 항균활성을 나타내는 것으로 보고되어 있는 2,3-dihydro-benzofuran, 4-hydroxy-3-methoxy- benzoic acid와 4-hydroxy benzeneethanol 등의 성분들이 검출되었다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.344-353
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• 2020

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

• 분석과학
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• 제8권4호
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• pp.545-551
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• 1995

Five acid hydrazides as precolumn fluorescence derivatization reagents for carboxylic acids in HPLC, which have the benzofuran or benzothiazole moiety conjugated to a furan, thiophene or oxazoline ring, were synthesized and examined in view of reactivity, separability and sensitivity. Of these hydrazides, 2-(5-hydrazinocarbonyl-2-oxazolyl)-5,6-dimethoxybenzothiazole (BTOH) was most favorable. The detection limit of lauric acid as a model acid was 0.1 pmol per $10-{\mu}l$ injection volume at S/N=3, which was roughly equal to that of an analogous compound, 2-(5-hydrazinocarbonyl-2-furyl)-5,6-dimethoxybenzothiazole. The reagent allowed rapid assays of carboxylic acids ($C_{12:0}-C_{20:4}$) within 20 min with satisfactory scparability. The method was applied to the determination of fatty acids in human sera from healthy volunteers as well as from patients with diabetes or thyroid dysfunction.