title: Design and synthesis of 2,3-dihydro- and 5-chloro-2,3-dihydro-naphtho-[1,2-b]furan-2-carboxylic acid N-(substitutedphenyl)amide analogs and their biological activities as inhibitors of NF-κB activity and anticancer agents.
abstract: A series of 2,3-dihydro- and 5-chloro-2,3-dihydro-naphtho-[1,2-b]furan-2-carboxylic acid N-(substitutedphenyl)amide analogs (1a-k and 2a-i) were designed and synthesized for developing novel naphthofuran scaffolds as anticancer agents and inhibitors of NF-κB activity. Compound 1d, which had a 4'-chloro group on the N-phenyl ring, exhibited inhibitory activity of NF-κB. Compound 2g, which had a 5'-chloro group on the naphthofuran ring and a 3',5'-bistrifluoromethane group on the N-phenyl ring, had the best NF-κB inhibitory activity. In addition, the novel analogs exhibited potent cytotoxicity at low concentrations against HCT-116, NCI-H23, and PC-3 cell lines. The two electron-withdrawing groups, especially at the 3',5'-position on the N-phenyl ring, increased anticancer activity and NF-κB inhibitory activity. However, only 5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxylic N-(3',5'-bis(trifluoromethyl)phenyl)amide (2g) exhibited both outstanding cytotoxicity and NF-κB inhibitory activities. This novel lead scaffold may be helpful for investigation of new anticancer agents by inactivation of NF-κB.
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Hyeju
authors.initials: H
authors.lastname: Jo
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Dayoung
authors.initials: D
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, 28116, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, 28116, Republic of Korea.
authors.forename: Jong-Soon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, 10326, Republic of Korea.
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Kyungsung University, Busan, 48434, Republic of Korea. jhkwak@ks.ac.kr.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk, 28644, Republic of Korea. medchem@chungbuk.ac.kr.
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D016328:NF-kappa B; D009281:Naphthalenes
keywords: 2,3-Dihydronaphtho-[1,2-b]furan scaffolds; Anticancer activity; Inhibition of NF-κB transcriptional activity