Structure-cytotoxic activity relationship of sesquilignan, morinol A.

Bioorganic & medicinal chemistry letters

PubMedID: 23896495

Yamauchi S, Kawahara S, Wukirsari T, Nishiwaki H, Nishi K, Sugahara T, Akiyama K, Kishida T. Structure-cytotoxic activity relationship of sesquilignan, morinol A. Bioorg Med Chem Lett. 2013;23(17):4923-30.
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=24-35µM). 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=6-7µM). 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=6µM) against HeLa cells. Against HL-60 cells, 7?-(4-nitrophenyl)-7,7'-phenyl derivative 33 and 7?-hexyl-7,7'-phenyl derivative 37 (IC50=5µM) 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.