title: Novel daidzein analogs and their in vitro anti-influenza activities.
abstract: A series of novel isoflavonoids were synthesized based on structural modifications of daidzein, an active ingredient of traditional Chinese medicine (TCM) and evaluated for their anti-influenza activity, in vitro, against H1N1 Tamiflu-resistant (H1N1 TR) virus in the MDCK cell line. Among them, 4-oxo-4H-1-benzopyran-8-carbaldehydes 11a-11g were most promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent. 3-(4-Bromophenyl)-7-hydroxy-4-oxo-4H-1-benzopyran-8-carboxaldehyde (11c) displayed the best inhibitory activity (EC50 , 29.0 μM) and selectivity index (SI>10.3). Analysis of the structureactivity relationships (SAR) indicated that both the non-naturally-occurring Br-substituted B-ring and appropriate CHO and OH groups on the A-ring might be critical for the activity and selectivity against H1N1 TR influenza viruses.
authors: Institute of Medical Sciences, National Defense Medical Center, 161 Minchuan East Rd. Sec. 6, Taipei, 11490, Taiwan.
authors: Shu-Ting
authors: ST
authors: Chung
authors: Yi-Ting
authors: YT
authors: Huang
authors: Hsin-Yi
authors: HY
authors: Hsiung
authors: Wen-Hsin
authors: WH
authors: Huang
authors: Chen-Wen
authors: CW
authors: Yao
authors: An-Rong
authors: AR
authors: Lee
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D024882:Drug Resistance, Viral / Q000187:drug effects; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D061985:Madin Darby Canine Kidney Cells / Q000187:drug effects / Q000821:virology; D015394:Molecular Structure; D053139:Oseltamivir / Q000494:pharmacology; D012254:Ribavirin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D007529:Isoflavones; D053139:Oseltamivir; D012254:Ribavirin; C004742:daidzein
keywords: Anti-influenza virus; Daidzein; H1N1 Tamiflu-resistant virus; Isoflavonoids