Structure-Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities.
Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4-8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (-)-epigallocatechin-[4,8]-(+)-catechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(-)-epigallocatechin and performed structure-activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity.
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. me14a007@oecu.jp.
Yoshitomo
Y
Hamada
Faculty of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. eg10a032@osakac.info.
Syota
S
Takano
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. me14a001@oecu.jp.
Yoshihiro
Y
Ayano
Faculty of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. eu11a066@oecu.jp.
Masahiro
M
Tokunaga
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. me14a005@oecu.jp.
Takahiro
T
Koashi
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. me12a003@oecu.jp.
Syuhei
S
Okamoto
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. me12a008@oecu.jp.
Syoma
S
Doi
Faculty of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. eg10a006@osakac.info.
Masahiko
M
Ishida
Department of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan. kawa0227@fc.ritsumei.ac.jp.
Takashi
T
Kawasaki
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180, Kurokawa, Imizu, Toyama 939-0398, Japan. hamada@pu-toyama.ac.jp.
Masahiro
M
Hamada
Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180, Kurokawa, Imizu, Toyama 939-0398, Japan. nori@pu-toyama.ac.jp.
Noriyuki
N
Nakajima
Graduate School of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. a-saito@isc.osakac.ac.jp.|Faculty of Engineering, Osaka Electro-Communication University (OECU), 18-8 Hatsu-cho, Neyagawa-shi, Osaka 572-8530, Japan. a-saito@isc.osakac.ac.jp.
Akiko
A
Saito
D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D010851:Picrates / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D005419:Flavonoids; D016166:Free Radical Scavengers; D005609:Free Radicals; D010851:Picrates; C404987:flavan-3-ol; C004931:1,1-diphenyl-2-picrylhydrazyl
DPPH radical scavenging activity; antimicrobial activity; cancer cell proliferation inhibitory activity; condensed tannins; oligomeric flavonoid; synthesis