title: Structure-cytotoxic activity relationship of sesquilignan, morinol A.
abstract: The cytotoxic activities of sesquilignans, (7S,8S,7'R,8'R)- and (7R,8R,7'S,8'S)-morinol A and (7S,8S,7'S,8'S)- and (7R,8R,7'R,8'R)-morinol B were compared, showing no significant difference between stereoisomers (IC50=24-35 μM). As a next stage, the effect of substituents at 7, 7', and 7"-aromatic ring on the activity was evaluated to find out the higher activity of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18 (IC50=6-7 μM). In the research on the structure-activity relationship of 7"-position of (7S,8S,7'R,8'R)-7,7',7"-phenyl derivative 18, the most potent compounds were 7,7',7"-phenyl derivative 18 (IC50=6 μM) against HeLa cells. Against HL-60 cells, 7"-(4-nitrophenyl)-7,7'-phenyl derivative 33 and 7"-hexyl-7,7'-phenyl derivative 37 (IC50=5 μM) showed highest activity. We discovered the compounds showed four to sevenfold potent activity than that of natural (7S,8S,7'R,8'R)-morinol A. It was also confirmed that the 7'-benzylic hydroxy group have an important role for exhibiting activity, on the other hand, the resonance system of cinnamyl structure is not crucial for the potent activity.
authors.affiliation: Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan. syamauch@agr.ehime-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamauchi
authors.forename: Saya
authors.initials: S
authors.lastname: Kawahara
authors.forename: Tuti
authors.initials: T
authors.lastname: Wukirsari
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nishiwaki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Nishi
authors.forename: Takuya
authors.initials: T
authors.lastname: Sugahara
authors.forename: Koichi
authors.initials: K
authors.lastname: Akiyama
authors.forename: Taro
authors.initials: T
authors.lastname: Kishida
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D011714:Pyrans / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D017705:Lignans; D011714:Pyrans; C519741:morinol A; C519740:morinol B
keywords: Cytotoxic activity; Lignan; Morinol; Sesquilignan