Yoon, Sung Hwa Lee, Eunhwa Cho, Duk Yeon Ko, Hyun Myung Baek, Ha Yeon Choi, Dong Kug Kim, Eunha Park, Ju Young 2021-03-15 1464-3405 https://aurora.ajou.ac.kr/handle/2018.oak/31805 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85099921614&origin=inward Based on our previous report that 3-morpholino-1-phenylpropan-1-one 2, one of the fluoxetine's simplified morpholino analogue, inhibited nitric oxide (NO) production, in this paper, various substituted benzene analogues with morpholine hydrochloride of 2 were synthesized and their inhibitory effects on NO production in lipopolysaccharide (LPS)-induced BV2 cells were tested. Among the synthesized compounds, 2-trifluoromethyl analogue 16n (IC50 = 8.6 μM) showed a significantly higher inhibitory activity than that of the parent compound 2a (IC50 > 50 μM) and suppressed NO production dose-dependently without cytotoxicity. Compound 16n also inhibited iNOS expression in LPS-induced BV2 cells at 2, 10 and 20 μM concentrations. These results suggest that compound 16n inhibited NO production by suppressing the expression of iNOS and can be used as a lead structure for developing new inhibitor of NO production. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education [ NRF-2020R1A2B5B02002032 (to S.-H Yoon and D.-K Choi) and ( NRF-2020R1I1A1A01062002 and 2019R1A6A1A11051471 (to J.-Y Park)]. eng Elsevier Ltd Animals Cell Line Chlorides Dose-Response Relationship, Drug Lipopolysaccharides Mice Molecular Structure Morpholines Nitric Oxide Structure-Activity Relationship Synthesis of 4-(3-oxo-3-phenylpropyl)morpholin-4-ium chloride analogues and their inhibitory activities of nitric oxide production in lipopolysaccharide-induced BV2 cells Article Bioorganic and Medicinal Chemistry Letters 36 Bioorganic and Medicinal Chemistry Letters, Vol.36 10.1016/j.bmcl.2021.127780 33422605 2-s2.0-85099921614 http://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters/ 3-Morpholino-1-phenylpropan-1-one analogues BV2 cell NO production Article 0960894X false Biochemistry Molecular Medicine Molecular Biology Pharmaceutical Science Drug Discovery Clinical Biochemistry Organic Chemistry