TY - JOUR
T1 - Antitumor Potential of the Isoflavonoids (+)- And (-)-2,3,9-Trimethoxypterocarpan
T2 - Mechanism-of-Action Studies
AU - Farias, Kaio
AU - Da Costa, Roner F.
AU - Meira, Assuero S.
AU - Diniz-Filho, Jairo
AU - Bezerra, Eveline M.
AU - Freire, Valder N.
AU - Guest, Prue
AU - Nikahd, Maryam
AU - Ma, Xinghua
AU - Gardiner, Michael G.
AU - Banwell, Martin G.
AU - Banwell, Martin G.
AU - De Oliveira, Maria Da C.F.
AU - De Moraes, Manoel O.
AU - Do Ó Pessoa, Claudia
N1 - Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/6/11
Y1 - 2020/6/11
N2 - Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(-)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.
AB - Synthetically derived samples of (+)-(6aS,11aS)-2,3,9-trimethoxypterocarpan [(+)-1] and its enantiomer [(-)-1], both of which are examples of naturally occurring isoflavonoids, were evaluated, together with the corresponding racemate, as cytotoxic agents against the HL-60, HCT-116, OVCAR-8, and SF-295 tumor cell lines. As a result it was established that compound (+)-1 was particularly active with OVCAR-8 cells being the most sensitive and responding in a dose-dependent manner. A study of cell viability and drug-induced morphological changes revealed the compound causes cell death through a mechanism characteristic of apoptosis. Finally, a computational study of the interactions of compound (+)-1 and (S)-monastrol, an established, synthetically derived, potent, and cell-permeant inhibitor of mitosis, with the kinesin-type protein Eg5 revealed that both bind to this receptor in a similar manner. Significantly, compound (+)-1 binds with greater affinity, an effect attributed to the presence of the associated methoxy groups.
KW - Anticancer agents
KW - Eg5
KW - OVCAR-8 cell-line
KW - molecular docking
KW - pterocarpan
UR - http://www.scopus.com/inward/record.url?scp=85087154680&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.0c00097
DO - 10.1021/acsmedchemlett.0c00097
M3 - Article
SN - 1948-5875
VL - 11
SP - 1274
EP - 1280
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 6
ER -