Hardness controlled enzymes and electronegativity controlled enzymes: role of an absolute hardness-electronegativity (eta-chi) activity diagram as a coordinate for biological activities.
We found that absolute hardness-absolute electronegativity (eta-chi) activity diagrams play an important role as a new coordinate of bioactivity in structure-activity relationships. In this paper, the eta-chi activity diagram, focusing on the molecular mechanism of bioactive compounds is used to discuss two major problems. First, the potency of bioactivities for xenobiotics such as polychlorinated dibenzo-p-dioxins (PCDDs) 3 and polychlorinated biphenyls (PCBs) 4, were found to be strongly related to their absolute hardness (eta). Second, the antibacterial activity of new quinolones such as norfloxacin 1 and enoxacin 2, was found to be strongly related to their absolute electronegativity (chi). These findings predict at least two chemical properties for a hardness-controlled or electronegativity-controlled enzyme.
Department of Drug Analysis, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
S
S
Kobayashi
H
H
Hamashima
M
M
Kurihara
N
N
Miyata
A
A
Tanaka
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004147:Dioxins / Q000737:chemistry / Q000494:pharmacology; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D006244:Hardness; D008968:Molecular Conformation; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D042462:4-Quinolones; D000890:Anti-Infective Agents; D004147:Dioxins; D004791:Enzyme Inhibitors; D004798:Enzymes; D018336:Receptors, Aryl Hydrocarbon; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D011078:Polychlorinated Biphenyls