Antitumor Potential of the Isoflavonoids (+)- and (-)-2,3,9-Trimethoxypterocarpan: Mechanism-of-Action Studies
Date
2020
Authors
Farias, Kaio
da Costa, Roner F
Meira, Assuero
Diniz-Filho, Jairo
Bezerra, Eveline M
Freire, Valder N
Guest, Prudence
Nikahd, Maryam
Ma, Xing
Gardiner, Michael
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Volume Title
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American Chemical Society
Abstract
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
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Keywords
Anticancer agents, Eg5, molecular docking, OVCAR-8 cell-line, pterocarpan
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ACS Medicinal Chemistry Letters
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Journal article
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2099-12-31
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