Publications by authors named "Chang Sang Moon"

3 Publications

  • Page 1 of 1

Discovery of N-amido-phenylsulfonamide derivatives as novel microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors.

Bioorg Med Chem Lett 2021 06 26;41:127992. Epub 2021 Mar 26.

Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:

Our previous research showed that N-carboxy-phenylsulfonyl hydrazide (scaffold A) could reduce LPS-stimulated PGE levels in RAW 264.7 macrophage cells by an inhibition of mPGES-1 enzyme. However, a number of scaffold A derivatives showed the drawbacks such as the formation of regioisomers and poor liver metabolic stability. In order to overcome these synthetic and metabolic problems, therefore, we decided to replace N-carboxy-phenylsulfonyl hydrazide (scaffold A) with N-carboxy-phenylsulfonamide (scaffold B) or N-amido-phenylsulfonamide frameworks (scaffold C) as a bioisosteric replacement. Among them, MPO-0186 (scaffold C) inhibited the production of PGE (IC: 0.24 μM) in A549 cells via inhibition of mPGES-1 (IC: 0.49 μM in a cell-free assay) and was found to be approximately 9- and 8-fold more potent than MK-886 as a reference inhibitor, respectively. A molecular docking study theoretically suggests that MPO-0186 could inhibit PGE production by blocking the PGH binding site of mPGES-1 enzyme. Furthermore, MPO-0186 demonstrated good liver metabolic stability and no significant inhibition observed in clinically relevant CYP isoforms except CYP2C19. This result provides a potential starting point for the development of selective and potent mPGES-1 inhibitor with a novel scaffold.
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http://dx.doi.org/10.1016/j.bmcl.2021.127992DOI Listing
June 2021

Synthesis and anticancer activity of chromone-based analogs of lavendustin A.

Eur J Med Chem 2010 Sep 25;45(9):4288-92. Epub 2010 Jun 25.

Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, Republic of Korea.

Lavendustin A and hormothamnione were reported to exhibit cytotoxic effects on tumor cell lines. In the present studies, a series of chromone-based lavendustin analogs were synthesized as a simplified hybrid of hormothamnione and lavendustin A by the reductive-amination of formyl-chromone 5 with various amines followed by aminoalkylation. Most compounds synthesized showed significantly improved potencies compared to the standard compound 3 against most of cancer cell lines tested indicating that the removal of styryl group enhanced cancer cell growth inhibitory activities. Compound 4h and 4k showed the most potent inhibitory activities with GI(50) values in the range of 6.01-9.92 microg/ml on A-549 and HCT-15 cells.
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http://dx.doi.org/10.1016/j.ejmech.2010.06.030DOI Listing
September 2010

Synthesis and anticancer activity of lavendustin A derivatives containing arylethenylchromone substituents.

Eur J Med Chem 2006 Aug 9;41(8):991-6. Epub 2006 Jun 9.

Kyung Hee East-West Pharmaceutical Research Institute and Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-Dong, Seoul 130-701, South-Korea.

2-Styrylchromones, which are relatively scarce in nature, have been reported to possess potent cytotoxicities on KB cell line. Lavendustin A, a metabolite of Streptomyces griseolavendus, has been shown to inhibit a growth of A431 cell line. Accordingly, a series of compounds 3a-g having structural features of styrylchromones and lavendustin A were synthesized and evaluated for cytotoxicity using SRB assay on four tumor cell lines. Compounds 3a-g were synthesized by the condensation of 2-methylchromone derivative 7 with several aromatic aldehydes. Among synthesized, compound 3e showed the significant cytotoxic activity on HCT-15 cell line with IC(50) values of 7.17 microg/ml indicating that lavendustin A derivatives containing 2-arylethenylchromone ring have a potential in anti-tumor application.
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http://dx.doi.org/10.1016/j.ejmech.2006.04.008DOI Listing
August 2006
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