Tryptophan-derived Alkaloids from Hedera rhombea Fruits and Their Butyrylcholinesterase Inhibitory Activity

Manh Tuan Ha,박세은,김정아,우미희,Jae Sue CHOI,민병선 한국생약학회 2022 Natural Product Sciences Vol.28 No.3

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease in industrialized countries. It is estimated that about 47 million people living with dementia and the number of cases will be tripled by 2050. However, the exact mechanism of AD is not known, and full therapy has still not been found. Various tryptophan-derived alkaloids have been reported as promising agents for the treatment of AD. In the present study, a series of tryptophan-derived alkaloids were isolated and characterized from the methanol extract of Hedera rhombea fruit. Based on the analysis of their observed and reported spectroscopic data, their structures were identified as N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan (1), N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan (2), N-[4′-hydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (3), and N-[3′,4′-dihydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (4). These compounds were screened for anti-Alzheimer activity via their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro. As a result, compounds 3 and 4 showed moderate BChE inhibition with IC50 values of 86.9 and 78.4 µM, respectively, compared to those of the positive control [berberine (IC50 = 11.5 µM)]. However, all four compounds did not show significant inhibition of the AChE enzyme. This is the first time, the AChE and BChE inhibitory activities of these tryptophan-derived alkaloids were investigated and reported.

Elastic structure for a multi-axis forcetorque sensor

Manh-Tuan Ha,강철구 대한기계학회 2020 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.34 No.1

The multi-axis force–torque sensor is a key element of many accurate force and motion control systems, including intelligent robotic systems. This paper presents a novel elastic structure for multi-axis force–torque sensors that is easily manufacturable at low cost and has many detection points with high surface strains. By using the “design of experiment” method in the ANSYS software, we demonstrate that the designed elastic structure with four identical T-shapes has high surface strains and can provide various strain gauge configurations. The strain sensitivities of the elastic structure at predetermined points can be maximized manually by varying the thickness of the vertical and horizontal beams of the T-shaped components. The validity of the proposed elastic structure is demonstrated through the development of a low-cost six-axis force–torque sensor. Experimental results for the developed force–torque sensor with the proposed elastic structure demonstrate that the proposed structure is comparable to an expensive state-of-the-art commercial force–torque sensor.

Fatigue Analysis of Railway Wheels according to UIC Standards

Manh-Tuan Ha,Chul-Goo Kang 제어로봇시스템학회 2012 제어로봇시스템학회 국제학술대회 논문집 Vol.2012 No.10

Wheelsets of a train experience a high cyclic load in normal operation and the fatigue analysis of the wheel is crucially important in view of safety of the train. This paper presents a methodology to verify the fatigue safety of the rolling wheels, which is a part of wheelset design process. Recently, the fatigue analysis of the wheel is conducted mainly based on UIC Code criterion, which is complex to apply to actual wheels. In this paper, a 3D model of the railway wheel is analyzed using ANSYS FEM software via uni-axial criterion and multi-axial Crossland criterion.

A Precision Stopping Measurement Device for Data Acquisition of Urban Trains

Manh-Tuan Ha,Chul-Goo Kang,Ho-Yeon Kim,Tae Hoi An 제어로봇시스템학회 2014 제어로봇시스템학회 국제학술대회 논문집 Vol.2014 No.10

Precision stopping of an urban train at a station is prerequisite before starting revenue service due to screen doors. Regulation for precision stopping of the urban train requires ±30 cm in general in Korea. Since there is no device to detect stopping error automatically, it takes long time to gather stopping error data at each station due to manual measurement using a ruler. In this paper, we present a principle and design of a precision stopping measurement device (PSMD) which can be easily used for error detection of precision stopping of urban trains. The PSMD developed in our laboratory uses a non-contact optical laser sensor installed at the platform to generate pulse signals from vertical black and white patterns attached on a train side. The number of the generated pulses is counted using a microcontroller, and then is sent to a notebook computer on the train via wireless RF communication. The performance of the PSMD is tested at the lab experimentally under indoor and outdoor environments.

Versatile Temperature Control System for Strain Gage Curing

Manh-Tuan Ha,Song-Hak Cheon,Chul-Goo Kang 제어로봇시스템학회 2016 제어로봇시스템학회 국제학술대회 논문집 Vol.2016 No.10

For the production of strain gage transducers, hot curing adhesives are generally used to ensure complete transfer of the strain from the measurement object surface into the strain gages. Optimum temperature curves for hot curing and postcuring of strain gage installation are different according to adhesive models and manufactures. Commercial curing ovens with temperature control functions are expensive in general to buy. Thus, in this paper, we develop a cheap but versatile temperature-controlled oven system for strain gage installation using an oven and a thermocouple, which is small, light and easy to use, and can be applied to almost all kinds of adhesives and strain gages. The performance of the developed temperature-controlled oven system for strain gage curing has been demonstrated by experimental works.

A Motion Control System Developed for Research and Education Purposes

Manh-Tuan Ha,Chul-Goo Kang 제어로봇시스템학회 2013 제어로봇시스템학회 국제학술대회 논문집 Vol.2013 No.10

Research and education on motion control requires an easy-to-use and economic experimental apparatus, but present commercial products are expensive, complex in mechanism and hard to use them in general. In this paper, we present an interesting motion control apparatus for research and education which is easy-to-use and economic. For user flexibility, we use an open-source free operation system Linux and a free real-time kernel RTAI. The developed motion control system is reliable in mechanism, and fast enough to implement 100 microsecond sampling time for real-time control. The developed motion control system has been demonstrated by testing PD (proportional-plus-derivative) control and ZV (zero vibration) input shaping experimentally.

Chalcone derivatives from the root bark of <i>Morus alba</i> L. act as inhibitors of PTP1B and <i>α</i>-glucosidase

Ha, Manh Tuan,Seong, Su Hui,Nguyen, Tien Dat,Cho, Won-Kyung,Ah, Kim Jeong,Ma, Jin Yeul,Woo, Mi Hee,Choi, Jae Sue,Min, Byung Sun Elsevier 2018 Phytochemistry Vol.155 No.-

<P><B>Abstract</B></P> <P>As part of our continuing research to obtain pharmacologically active compounds from <I>Morus alba</I> L. (Moraceae), four Diels-Alder type adducts (DAs) [morusalbins A−D], one isoprenylated flavonoid [albanin T], together with twenty-one known phenolic compounds were isolated from its root bark. The chemical structures were established using NMR, MS, and ECD spectra. The DAs including morusalbins A−D, albasin B, macrourin G, yunanensin A, mulberrofuran G and K, and albanol B exhibited strong inhibitory activities against both protein tyrosine phosphatase 1B (PTP1B) (IC<SUB>50</SUB>, 1.90<B>−</B>9.67 μM) and α-glucosidase (IC<SUB>50</SUB>, 2.29<B>−</B>5.91 μM). In the kinetic study, morusalbin D, albasin B, and macrourin G showed noncompetitive PTP1B inhibition, with <I>K</I> <SUB> <I>i</I> </SUB> values of 0.33, 1.00, and 1.09 μM, respectively. In contrast, these DAs together with yunanensin A produced competitive inhibition of <I>α</I>-glucosidase, with <I>K</I> <SUB> <I>i</I> </SUB> values of 0.64, 0.42, 2.42, and 1.19 μM, respectively. Furthermore, molecular docking studies revealed that these active DAs have high affinity and tight binding capacity towards the active site of PTP1B and <I>α</I>-glucosidase.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>.</I>Four Diels-Alder adducts (DAs) and one isoprenylated flavonoid were isolated from <I>Morus alba</I> </LI> <LI> Absolute configuration of DAs with a bicyclo[3.3.1] core was confirmed for the first time by calculated ECD. </LI> <LI> Some of the DAs showed potent inhibition of both PTP1B and α-glucosidase. </LI> <LI> The active DAs could act as dual allosteric PTP1B/ catalytic <I>α</I>-glucosidase inhibitors. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Four Diels-Alder adducts, one isoprenylated flavonoid, and 21 known phenolic compounds were isolated from <I>Morus alba</I> root bark. The active Diels-Alder adducts could act as dual allosteric PTP1B/catalytic <I>α</I>-glucosidase inhibitors.</P> <P>[DISPLAY OMISSION]</P>

PTP1B inhibitory activity and molecular docking analysis of stilbene derivatives from the rhizomes of <i>Rheum undulatum</i> L.

Ha, Manh Tuan,Park, Dong Hwa,Shrestha, Srijan,Kim, Minji,Kim, Jeong Ah,Woo, Mi Hee,Choi, Jae Sue,Min, Byung Sun Elsevier 2018 Fitoterapia Vol.131 No.-

<P><B>Abstract</B></P> <P>Stilbene derivatives, the principal constituent of <I>Rheum undulatum</I> L., are known to have a wide range of biological activities, such as anti-allergic, anti-diabetic, antioxidant, and anti-inflammatory activities. A phytochemical study on the methanol extract of Korean rhubarb (<I>R. undulatum</I> L.) led to the isolation of nine stilbene derivatives (<B>1</B>–<B>9</B>) and one flavonoid (<B>10</B>). All structures were elucidated based on a comprehensive analysis of spectroscopic data. Compound <B>1</B> (5-methoxy-<I>cis</I>-rhapontigenin) was elucidated as a new compound, while compound <B>2</B> (5-methoxy-<I>trans</I>-rhapontigenin) was isolated from a natural source for the first time. Among the isolated compounds, stilbene derivatives (<B>7</B>–<B>9</B>) showed a strong inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) with IC<SUB>50</SUB> values ranging from 4.25 to 6.78 μM, which was significantly higher than that of the positive control, ursolic acid (IC<SUB>50</SUB> = 11.34 μM). Furthermore, for the first time, kinetic analysis and molecular docking simulations were performed in order to understand the inhibition type as well as the interaction and binding mode of the active stilbenes (<B>7</B>–<B>9</B>) with PTP1B. Our results showed that the types of PTP1B inhibition were noncompetitive for ɛ-viniferin (<B>8</B>) and mixed for piceatannol (<B>7</B>) and δ-viniferin (<B>9</B>). Docking simulations of these stilbenes demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Trichosanhemiketal A and B: Two 13,14-<i>seco</i>-13,14-epoxyporiferastanes from the root of <i>Trichosanthes kirilowii</i> Maxim.

Ha, Manh Tuan,Phan, Thanh Nam,Kim, Jeong Ah,Oh, Won Keun,Lee, Jeong Hyung,Woo, Mi Hee,Min, Byung Sun Elsevier 2019 Bioorganic chemistry Vol.83 No.-

<P><B>Abstract</B></P> <P>Of the 32 <I>Trichosanthes</I> species in China, <I>T. kirilowii</I> Maxim. is the most renowned species used in traditional Chinese medicine and has diverse pharmacological properties. However, most of the phytochemical studies of <I>T. kirilowii</I> have focused on the fruits and seeds. In our investigation of the chemical constituents of <I>T. kirilowii</I> roots, two previously undescribed sterols [trichosanhemiketal A and B (<B>1</B> and <B>2</B>)], together with 13 known compounds, were isolated and their structures were elucidated. To the best of our knowledge, this represents the first isolation of compounds with a 13,14-<I>seco</I>-13,14-epoxyporiferastane (<B>1</B>–<B>2</B>) skeleton from the Cucurbitaceae family. The anti-inflammatory activity of the isolated compounds was determined through an analysis of their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Of the compounds, <B>4</B>, <B>5</B>, <B>6</B>, and <B>8</B> showed significant inhibitory activities, with IC<SUB>50</SUB> values of 8.5, 15.1, 25.4, and 28.5 µM, respectively. In addition, compound <B>4</B> inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in a concentration-dependent manner.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Two new sterols [trichosanhemiketal A, B; (<B>1</B>–<B>2</B>)] and 13 known compounds were isolated from <I>Trichosanthes kirilowii</I> root. </LI> <LI> The 13,14-<I>seco</I>-13,14-epoxyporiferastane skeleton (<B>1</B>–<B>2</B>) was found from the Cucurbitaceae family for the first time. </LI> <LI> Cucurbitacins <B>4</B>, <B>5</B>, <B>6</B>, and <B>8</B> showed significant NO inhibitory activities. </LI> <LI> Compound <B>4</B> inhibited inducible iNOS and COX-2 expression. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of <i>Erythrophleum fordii</i>

Ha, Manh Tuan,Tran, Manh Hung,Phuong, Thien Thuong,Kim, Jeong Ah,Woo, Mi Hee,Choi, Jae Sue,Lee, Suhyun,Lee, Jeong Hyung,Lee, Hyeong Kyu,Min, Byung Sun Elsevier 2017 Bioorganic & medicinal chemistry letters Vol.27 No.13

<P><B>Abstract</B></P> <P>A phytochemical investigation into the bark of <I>Erythrophleum fordii</I> yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, <B>1</B> and <B>2</B>) and two new cassaine diterpenoid amines (erythroformine A and B, <B>6</B> and <B>7</B>), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (<B>3</B>) from a natural source and that of the remaining eight known diterpenoids (<B>4</B>–<B>5</B>, <B>8</B>–<B>13</B>) from <I>E. fordii</I>. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (<B>1</B>–<B>13</B>) was examined <I>in vitro</I> against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (<B>6</B>–<B>10</B>, <B>12</B>, <B>13</B>) exhibited potent cytotoxic activity against all three cell lines with IC<SUB>50</SUB> values between 0.4μM and 5.9μM. Erythroformine B (<B>7</B>) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>