개혁주의 교회의 영감론

C. Van Til,Conelius Van Til 신학지남사 1971 신학지남 Vol.38 No.1

Inhibitory Activity of Halogenated 3-Benzylidenechroman-4-ones Against Lipopolysaccharide-stimulated Reactive Oxygen Species Production in RAW 264.7 Macrophages

Til Bahadur Thapa Magar,KADAYAT TARAMAN,오혜진,박필훈,이응석 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.6

Chromanone-containing compounds have been reported to possess several important biological activities. As a part of our continuing effort for discovering potent anti-inflammatory agents, a series of halogen-containing 3-benzylidenechroman-4-ones (1–15) were synthesized, and evaluated for their inhibitory effect on lipopolysaccharide (LPS)-stimulated reactive oxygen species (ROS) production in RAW 264.7 macrophages. Compounds 4 and 10 exhibited significant inhibitory activity (IC50 = 5.09 ± 1.27 and 5.11 ± 0.51 μM, respectively) against LPS-stimulated ROS production in RAW 264.7 macrophages.

“Food for Thought”: Improving Cognition in People With Schizophrenia

Til Wykes 대한신경정신의학회 2024 PSYCHIATRY INVESTIGATION Vol.21 No.8

Objective We have known that cognitive difficulties are related to functional outcomes in schizophrenia for many years. However, we have only paid attention to potential treatments relatively recently, so implementation has been slow. Methods This is a narrative review describing the development of cognitive remediation treatments to improve cognitive skills and their effects on functioning. It also reviews the types of cognitive remediation with some evidence on their effects. Results Models of treatment have now been clarified and have led to a landmark paper by cognitive remediation experts around the world on the ingredients of cognitive remediation to produce the most benefit. This expert judgement on good clinical practice was justi-fied by a large meta-analysis that supported the extra benefit of the four ingredients: an active therapist, massed practice of cognitive skills, the teaching of cognitive strategies and additional rehabilitation to transfer skills to real life. Conclusion Although there is evidence of efficacy and of the beneficial therapy ingredients there is little implementation of cognitive re-mediation, so the establishment of cognitive remediation into mental health services needs an implementation pathway.

Synthesis and SAR study of new hydroxy and chloro-substituted 2,4-diphenyl 5<i>H</i>-chromeno[4,3-<i>b</i>]pyridines as selective topoisomerase IIα-targeting anticancer agents

Magar, Til Bahadur Thapa,Seo, Seung Hee,Kadayat, Tara Man,Jo, Hyunji,Shrestha, Aarajana,Bist, Ganesh,Katila, Pramila,Kwon, Youngjoo,Lee, Eung-Seok Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.8

<P><B>Abstract</B></P> <P>As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5<I>H</I>-chromeno[4,3-<I>b</I>]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα, and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound <B>11</B>, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds <B>8</B>–<B>18</B>, <B>22</B>, <B>24</B>, and <B>25</B> showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3′-, or 4′-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2′-substitution.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new series of hydroxy and chloro-substituted 2,4-diphenyl 5<I>H</I>-chromeno[4,3-<I>b</I>]pyridines were synthesized. </LI> <LI> Evaluated for topo I and IIα inhibitory activity, and antiproliferative activity. </LI> <LI> Compounds showed selective topo IIα inhibitory activity. </LI> <LI> SAR study indicated the importance of hydroxyphenyl-substitution at 4-position. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

2-Chlorophenyl-substituted benzofuro[3,2-<i>b</i>]pyridines with enhanced topoisomerase inhibitory activity: The role of the chlorine substituent

Thapa Magar, Til Bahadur,Kadayat, Tara Man,Lee, Hwa-Jong,Park, Seojeong,Bist, Ganesh,Shrestha, Aarajana,Kwon, Youngjoo,Lee, Eung-Seok Elsevier 2017 Bioorganic & medicinal chemistry letters Vol.27 No.15

<P><B>Abstract</B></P> <P>A new series of 2-chloropheny-substituted benzofuro[3,2-<I>b</I>]pyridines were designed, synthesized, and evaluated for topoisomerase I and II inhibition and antiproliferative activity. Compounds <B>17</B>–<B>19, 23, 24, 26,</B> and <B>27</B> exhibited excellent topo II inhibitory activity. A systematic structure-activity relationship study revealed the important role of chlorine substitution in the strong topoisomerase inhibitory activity.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

( Hye Jin Oh ),( Til Bahadur Thapa Magar ),( Nirmala Tilija Pun ),( Yunji Lee ),( Eun Hye Kim ),( Eung-seok Lee ),( Pil-hoon Park ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.2

Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.

YJI-7 Suppresses ROS Production and Expression of Inflammatory Mediators via Modulation of p38MAPK and JNK Signaling in RAW 264.7 Macrophages

Oh, Hye Jin,Magar, Til Bahadur Thapa,Pun, Nirmala Tilija,Lee, Yunji,Kim, Eun Hye,Lee, Eung-Seok,Park, Pil-Hoon The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.2

Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.

Rational design, synthesis, and evaluation of novel 2,4-Chloro- and Hydroxy-Substituted diphenyl Benzofuro[3,2-<i>b</i>]Pyridines: Non-intercalative catalytic topoisomerase I and II dual inhibitor

Park, Seojeong,Thapa Magar, Til Bahadur,Kadayat, Tara Man,Lee, Hwa Jong,Bist, Ganesh,Shrestha, Aarajana,Lee, Eung-Seok,Kwon, Youngjoo S.E.C.T. [etc.] 2017 European journal of medicinal chemistry Vol.127 No.-

<P><B>Abstract</B></P> <P>Novel series of conformationally constrained 2,4-chloro- and hydroxy-substituted diphenyl benzofuro[3,2-<I>b</I>]pyridines were rationally designed and synthesized. Their biological activities were evaluated for topoisomerase I and II inhibitory activity, and antiproliferative activity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds with phenol moiety at 4-position of central pyridine exhibited significant dual topoisomerase I and II inhibitory activities, and strong antiproliferative activity in low micromolar range. Structure activity relationship study suggested that phenol moiety at 4-position of the central pyridine regardless of chlorophenyl moiety at 2-position of the central pyridine has an important role in dual topoisomerase inhibitory activity as well as antiproliferative activity. For investigation of mode of action for compound <B>14</B> which displayed the most strong dual topoisomerase I and II inhibitory activity and antiproliferative activity against HCT15 cell, we performed cleavable complex assay, band depletion assay, comet assay, and competitive EtBr displacement assay. Compound <B>14</B> functioned as non-intercalative catalytic topo I and II dual inhibitor. In addition, compound <B>14</B> induced apoptosis in HCT15 cells through increase of Bax, decrease of Bcl-2 and increase of PARP cleavage.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A new class of dual topo inhibitors, 2,4-substituted diphenyl benzofuro[3,2-<I>b</I>]pyridines were prepared. </LI> <LI> Observed positive correlation with dual topo inhibition and antiproliferative activity. </LI> <LI> Benzofuran moiety and phenol on 4-position of central pyridine is crucial for both activity. </LI> <LI> Compound <B>14</B> acts as a non-intercalative catalytic dual topo I and II inhibitor. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A new anti-obesity medication with photodynamic therapy

Juhee Jeon,Shivkumar Shantappa Jalde,Til Bahadur Thapa Magar,CheongWun Kim,Bo-Mi Lee,Yong-Wan Kim 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.1

Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and IIα dual inhibitors with DNA non-intercalative catalytic activity

Bist, Ganesh,Park, Seojeong,Song, Chanju,Thapa Magar, Til Bahadur,Shrestha, Aarajana,Kwon, Youngjoo,Lee, Eung-Seok S.E.C.T. [etc.] 2017 European journal of medicinal chemistry Vol.133 No.-

<P><B>Abstract</B></P> <P>With the aim to develop novel antiproliferative agents, a new series of eighteen dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines were systematically designed, prepared, and investigated for their topoisomerase (topo) I and IIα inhibitory properties and antiproliferative effect in three different human cancer cell lines (HCT15, T47D, and HeLa). Compounds <B>22–30</B> which possess a <I>meta</I>- or <I>para</I>-phenol on 2-, or 6-position of central pyridine ring showed significant dual topo I and topo IIα inhibitory activities with strong antiproliferative activities against all the tested human cancer cell lines. However, compounds <B>13</B>–<B>21</B> which possess an <I>ortho</I>-phenol on 2-, or 6-position of central pyridine ring did not show significant topo I and topo IIα inhibitory activities but displayed moderate antiproliferative activities against all the tested human cancer cell lines. Compound <B>23</B> exhibited the highest antiproliferative potency as much as 348.5 and 105 times compared to etoposide and camptothecin, respectively, in T47D cancer cell line. The structure-activity relationship study revealed that the <I>para</I> position of a hydroxyl group at 2-and 6-phenyl ring and chlorine atom at the <I>para</I> position of 4-phenyl ring of the central pyridine exhibited the most significant topo I and topo IIα inhibition, which might indicate introduction of the chlorine atom at the phenyl ring of 4-pyridine have an important role as dual inhibitors of topo I and topo IIα. Compound <B>30</B> which showed the most potent dual topo I and topo IIα inhibition with strong antiproliferative activity in T47D cell line was selected to perform further study on the mechanism of action, which revealed that compound <B>30</B> functions as a potent DNA non-intercalative catalytic topo I and IIα dual inhibitor.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines were designed and synthesized. </LI> <LI> Introduction of chlorine on 4-phenyl ring of central pyridine showed strong dual topo I and IIα inhibitor. </LI> <LI> Compound <B>30</B> exhibited the most potent dual topo I and IIα inhibition with strong antiproliferative activity. </LI> <LI> Compound <B>30</B> acts as a DNA non-intercalative catalytic topo IIα inhibitor. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>