TY - JOUR
T1 - Structure-anti-MRSA activity relationship of macrocyclic bis(bibenzyl) derivatives
AU - Sawada, Hiromi
AU - Onoda, Kenji
AU - Morita, Daichi
AU - Ishitsubo, Erika
AU - Matsuno, Kenji
AU - Tokiwa, Hiroaki
AU - Kuroda, Teruo
AU - Miyachi, Hiroyuki
N1 - Funding Information:
This work was supported in part by the Drug Discovery for Intractable Infectious Diseases Project, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, the Uehara Memorial Foundation and a Grantin-aid for Scientific Research (C) (grant number 25460157 to H.T.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT). H.T. acknowledges MEXT Supported Program for the Strategic Research Foundation at Private Universities, 2013-2018. We also thank the SC-NMR Laboratory of Okayama University for NMR measurements.
PY - 2013/12/15
Y1 - 2013/12/15
N2 - We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The structure-activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A-B-benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity.
AB - We synthesized a series of macrocyclic bis(bibenzyl) derivatives, including riccardin-, isoplagiochin- and marchantin-class structures, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The structure-activity relationships and the results of molecular dynamics simulations indicated that bis(bibenzyl)s with potent anti-MRSA activity commonly have a 4-hydroxyl group at the D-benzene ring and a 2-hydroxyl group at the C-benzene ring in the hydrophilic part of the molecule, and an unsubstituted phenoxyphenyl group in the hydrophobic part of the molecule containing the A-B-benzene rings. Pharmacological characterization of the bis(bibenzyl) derivatives and 2-phenoxyphenol fragment 25, previously proposed as the minimum structure of riccardin C 1 for anti-MRSA activity, indicated that they have different action mechanisms: the bis(bibenzyl)s are bactericidal, while 25 is bacteriostatic, showing only weak bactericidal activity.
KW - Isoplagiochin
KW - Marchantin
KW - Methicillin resistance
KW - Riccardin
KW - Structure-activity relationship
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U2 - 10.1016/j.bmcl.2013.10.069
DO - 10.1016/j.bmcl.2013.10.069
M3 - Article
C2 - 24239015
AN - SCOPUS:84888860592
SN - 0960-894X
VL - 23
SP - 6563
EP - 6568
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 24
ER -