title: Design and synthesis of 3,4-dihydro-2H-benzo[h]chromene derivatives as potential NF-κB inhibitors.
abstract: A novel class of NF-κB inhibitors were designed and synthesized based on KL-1156 (6-hydroxy-7-methoxychroman-2-carboxylic acid phenyl amide) which is unambiguously considered to be a promising inhibitor for the translocation step of NF-κB. Especially in this study we focused on the modifying the chroman moiety of KL-1156 into four parts for exploring the SAR studies linked with physical properties of substituents resulted the development of novel 1a-k, 2a-f, 3a-d and 4a-d derivatives of 3,4-dihydro-2H-benzo[h]chromene. From the SAR studies we were very delightfully identified that several new N-aryl-3,4-dihydro-2H-benzo[h]chromene-2-carboxamide derivatives (1a-k) exhibited good inhibitory activity and anti-proliferative activity than parent lead compound KL-1156, among them 1i exhibited outstanding inhibitory effect on LPS-induced NF-κB transcriptional activity and anti-proliferative activity on NCI-H23 lung cancer cell lines than KL-1156.
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Minho
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Hwang
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Arepalli Sateesh
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Hyeju
authors.initials: H
authors.lastname: Jo
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Yeongeun
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Yunju
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Joonkwang
authors.initials: J
authors.lastname: Lee
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang 363-883, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Dongguk University, Goyang 410-773, Republic of Korea.
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
authors.affiliation: Department of Pharmacy, Chungbuk National University, Chungbuk 361-763, Republic of Korea. Electronic address: medchem@chungbuk.ac.kr.
authors.forename: Heesoon
authors.initials: H
authors.lastname: Lee
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001578:Benzopyrans; C000593984:N-(2-(trifluoromethyl)phenyl)-3,4-dihydro-2H-benzo(h)chromene-2-carboxamide; D016328:NF-kappa B
keywords: Cytotoxic activity; N-Aryl-3,4-dihydro-2H-benzo[h]chromene-2-caboxamide derivatives; NF-κB inhibitors