Neuroprotective Coumarins from the Root of Angelica gigas: Structure-Activity Relationships

So Young Kang,Young Choong Kim 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae) exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Using neuroprotective activity-guided fractionation, nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-β-D-glucopyranoside (3), (S)-peucedanol-7-O-β-D-glucopyranoside (4), (S)- peucedanol-3'-O-β-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7), isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3, exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from 0.1 to 10 µM. To explore the structure-activity relationships of coumarins, sixteen previously isolated compounds; 10-25, were simultaneously evaluated in the same system. Our results revealed that cyclization of the isoprenyl group, such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of coumarin, as well as lipophilicity played an important role in the neuroprotective activity of coumarins.

Neuroprotective Coumarins from the Root of Angelica gigas: Structure-Activity Relationships

Kang, So-Young,Kim, Young-Choong 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

An n-butanol-soluble fraction of the root of Angelica gigas Nakai (Umbelliferae) exhibited significant protection against glutamate-induced toxicity in primary cultured rat cortical cells. Using neuroprotective activity-guided fractionation, nine coumarins; marmesinin (1), nodakenin (2), columbianetin-O-${\beta}$-D-glucopyranoside (3), (S)-peucedanol-7-${\beta}$-D-glucopyranoside (4), (S)-peucedanol-3'-${\beta}$-D-glucopyranoside (5), skimmin (6), apiosylskimmin (7), isoapiosylskimmin (8) and magnolioside (9), were isolated from the n-butanol fraction. Of these nine coumarins, three dihydrofuranocoumarins; 1, 2 and 3, exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viabilities of about 50% at concentrations ranging from 0.1 to $10{\mu}M$. To explore the structure-activity relationships of coumarins, sixteen previously isolated compounds; 10-25, were simultaneously evaluated in the same system. Our results revealed that cyclization of the isoprenyl group, such as dihydropyran or dihydrofuran, or the furan ring at the C-6 position of coumarin, as well as lipophilicity played an important role in the neuroprotective activity of coumarins.

쿠마린에 의한 RAW 264.7 세포주의 Nitric Oxide 생성 저해활성

노태철,최희철,김보연,김영호,안종석,김영국,이현선 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-

During the screening for inhibitors on nitric oxide (NO) producfion-in LPS-activated murine macrophage, RAW 264.7 cells, two coumarins were isolated from chloroform extract of Ponciri Fructus. They were identified as imperatorin (10), phellopterin (11) on the basis of spectroscopic methods. The IC_50 values for NO formatiom were about 5.4μM and 35.0μM, respectively, and then eleven coumarins were tested for the inhibitory effects on NO production in activated macrophages. All the test coumarins inhibited NO production in concentration-dependent manner and furanocoumarins (6-11) showed much more potent inhibitory effect than simple coumarins. Among the compounds examined xanthotoxin (8) was the most potent inhibitors of NO production (IC_50=1.4μM). Analysis of the structure-activity relationship among these coumarins led to the conclusion that the substitution of C-5 position in furanocoumarins reduces greatly their inhibitory potency although the substitution of C-8 does not almost affect it.

쿠마린에 의한 RAW 264.7 세포주의 Nitric Oxide 생성 저해활성

노태철,최희철,김보연,김영호,안종석,김영국,이현선,Rho, Tae-Cheol,Choi, Hee-Cheol,Kim, Bo-Yeon,Kim, Young-Ho,Ahn, Jong-Seog,Kim, Young-Kook,Lee, Hyun-Sun 한국생약학회 1999 생약학회지 Vol.30 No.4

During the screening for inhibitors on nitric oxide (NO) production in LPS-activated murine macrophage, RAW 264.7 cells, two coumarins were isolated from chloroform extract of Ponciri Fructus. They were identified as imperatorin (10), phellopterin (11) on the basis of spectroscopic methods. The $IC_{50}$ values for NO formatiom were about $5.4\;{\um}M$ and $35.0\;{\um}M$, respectively, and then eleven coumarins were tested for the inhibitory effects on NO production in activated macrophages. All the test coumarins inhibited NO production in concentration-dependent manner and furanocoumarins (6-11) showed much more potent inhibitory effect than simple coumarins. Among the compounds examined xanthotoxin (8) was the most potent inhibitors of NO production $(IC_{50}=1.4\;{\mu}M)$. Analysis of the structure-activity relationship among these coumarins led to the conclusion that the substitution of C-5 position in furanocoumarins reduces greatly their inhibitory potency although the substitution of C-8 does not almost affect it.

Solvent‑free Pechmann synthesis of coumarins catalyzed by magnetic heterogeneous catalyst Fe3O4@ rGO‑NH

Esmail Rezaei‑Seresht,Fatemeh Tafazzoli Gazkoh,Behrooz Maleki 한국탄소학회 2023 Carbon Letters Vol.33 No.1

This work describes the synthesis and characterization of a heterogeneous catalyst consisting of piperazine-functionalized reduced graphene oxide decorated with Fe3O4 nanoparticles ( Fe3O4@rGO-NH), and the study of its catalytic activity as a magnetic heterogeneous catalyst for the Pechmann synthesis of coumarins. Catalyst Fe3O4@ rGO-NH was fully characterized by various techniques, including IR, XRD, TEM, VSM, TGA, and elemental analysis. Then, the catalyst was used as an efficient and easy-separable heterogeneous catalyst for the solvent-free synthesis of some coumarins by Pechmann reaction. The reaction was optimized in terms of reaction time and temperature, catalyst dosage, and the presence/absence of the solvent. Finally, the reusability of the catalyst was studied.

Efficient Synthesis of Novel 3-Substituted Coumarin-3-carboxamide

Sheikhhosseini, Enayatollah,Balalaie, Saeed,Bigdeli, Mohammad Ali,Habibi, Azizollah,Moghaddam, Hamed Piri Korean Chemical Society 2014 대한화학회지 Vol.58 No.2

A series of novel pseudopeptides contained coumarin skeleton were synthesized through the Ugi-four-component reaction. The 3-substituted coumarin-3-carboxamides were formed through reaction of benzaldehyde derivatives, anilines, coumarin-3-carboxylic acid and isocyanides with high yields and high bond-forming efficiency at room temperature. These novel amidated coumarins exhibit brilliant fluorescence in range of 535-547 nm in chloroform.

Synthesis and Biological Evaluation of Decursin, Prantschimgin and Their Derivatives

Yan Xia,민경훈,Kyeong Lee 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.1

The synthesis of coumarin-based natural products and their derivatives is described. In vitro MDR reversal activities of the synthesized compounds were evaluated in P-glycoprotein over-expressing human sarcoma cell line MES-SA/DX5. Some of the coumarin derivatives were found to show potent MDR reversal activity. In particular, pyridyl derivative (15e) exhibited more potency than verapamil.

Synthesis and Biological Evaluation of Decursin, Prantschimgin and Their Derivatives

Xia, Yan,Min, Kyung-Hoon,Lee, Kyeong Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.1

The synthesis of coumarin-based natural products and their derivatives is described. In vitro MDR reversal activities of the synthesized compounds were evaluated in P-glycoprotein over-expressing human sarcoma cell line MES-SA/DX5. Some of the coumarin derivatives were found to show potent MDR reversal activity. In particular, pyridyl derivative (15e) exhibited more potency than verapamil.

Simultaneous determination of chromones and coumarins in Radix Saposhnikoviae by high performance liquid chromatography with diode array and tandem mass detectors

Kim, Min Kyung,Yang, Dong-Hyug,Jung, Mihye,Jung, Eun Ha,Eom, Han Young,Suh, Joon Hyuk,Min, Jung Won,Kim, Unyong,Min, Hyeyoung,Kim, Jinwoong,Han, Sang Beom Elsevier 2011 Journal of chromatography A Vol.1218 No.37

<P><B>Abstract</B></P><P>Methods using high performance liquid chromatography with diode array detection (HPLC-DAD) and tandem mass spectrometry (HPLC–MS/MS) were developed and validated for the simultaneous determination of 5 chromones and 6 coumarins: prim-<I>O</I>-glucosylcimifugin (1), cimifugin (2), nodakenin (3), 4′-<I>O</I>-β-<SMALL>D</SMALL>-glucosyl-5-<I>O</I>-methylvisamminol (4), sec-<I>O</I>-glucosylhamaudol (5), psoralen (6), bergapten (7), imperatorin (8), phellopterin (9), 3′-<I>O</I>-angeloylhamaudol (10) and anomalin (11), in Radix Saposhnikoviae. The separation conditions for HPLC-DAD were optimized using an Ascentis Express C18 (4.6mm×100mm, 2.7μm particle size) fused-core column. The mobile phase was composed of 10% aqueous acetonitrile (A) and 90% acetonitrile (B) and the elution was performed under a gradient mode at a flow rate of 1.0mL/min. The detection wavelength was set at 300nm. The HPLC-DAD method yielded a base line separation of the 11 components in 50% methanol extract of Radix Saposhnikoviae with no interfering peaks detected. The HPLC-DAD method was validated in terms of linearity, accuracy and precision (intra- and inter-day), limit of quantification (LOQ), recovery, and robustness. Specific determination of the 11 components was also accomplished by a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) source. This HPLC–MS/MS method was also validated by determining the linearity, limit of quantification, accuracy, and precision. Quantification of the 11 components in 51 commercial Radix Saposhnikoviae samples was successfully performed using the developed HPLC-DAD method. The identity, batch-to-batch consistency, and authenticity of Radix Saposhnikoviae were successfully monitored by the proposed HPLC-DAD and HPLC–MS/MS methods.</P>

당귀와 백지로부터 분리한 Coumarin계 물질들의 식물병원균에 대한 항균활성

유시용(Shi Yong Ryu),김진철(Jin-Cheol Kim),김영섭(Young Sup Kim),김흥태(Heung Tae Kim),김성기(Seong Kie Kim),최경자(Gyung Ja Choi),김정섭(Jeoung Seob Kim),이선우(Seon-Woo Lee),허정희(Junghee Heor),조광연(Kwang Yun Cho) 한국농약과학회 2001 농약과학회지 Vol.5 No.3

In order to search potent antifungal substances from domestic plants, 40 plants cultivated in Korea were collected. After extracting with methanol (MeOH) and concentrating to dryness, the MeOH extracts were screened for in vivo antifungal activity against six plant diseases at a concentration of 2000 ㎍/mL. Fourteen extracts showed disease-controlling activity more than 90% against at least one of the 6 plant diseases tested; eight, seven, and three extracts controlled more than 90% the development of rice blast, tomato late blight, and wheat leaf rust, respectively. However, none of the extracts exhibited in vivo antifungal activity more than 90% against rice sheath blight, tomato gray mold, and barley powdery mildew. From the MeOH extracts of Angelica gigas and A. dahurica showing potent controlling activity against rice blast, 1 and 2 antifungal substances, respectively, were isolated by solvent partitioning and column chromatography. The three compounds were identified to be coumarins, namely, decursin, imperatorin, and isoimperatorin, by mass spectrometry and NMR spectroscopy. They were examined for in vitro and in vivo antifungal activities together with umbelliferone (7-hydroxycournarin) and scopoletin (6-methoxy-7-hydroxycoumarin) containing a free hydroxyl group at position 7 to investigate the structure-activity relationship. In vitro, most of 50% growth inhibitory concentrations (IC??) were over 200 ㎍/mL, indicating that they have relatively weak antifungal activity. The antifungal activity of decursin and scopoletin, containing cyclic alkoxy groups instead of free hydroxyl group at position 7, was stronger than umbelliferone and scopoletin. Especially, decursin and imperatorin showed potent antifungal activities against Pythium ultimum and Magnaporthe grisea, respectively, with IC?? values less than 25 ㎍/mL. In vivo, decursin and imperatorin showed potent antifungal activity against rice blast, whereas other coumarins hardly controlled the development of 6 plant diseases tested. These results suggest that the antifungal activity of 7-hydroxycoumarin derivative is substantially increased when the hydroxyl group at position 7 is protected by a stable cyclic alkoxy grouping.