American Chemical Society
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Antitumor Potential of the Isoflavonoids (+)- and (−)-2,3,9-Trimethoxypterocarpan: Mechanism-of-Action Studies

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journal contribution
posted on 2020-05-27, 12:05 authored by Kaio Farias, Roner F. da Costa, Assuero S. Meira, Jairo Diniz-Filho, Eveline M. Bezerra, Valder N. Freire, Prue Guest, Maryam Nikahd, Xinghua Ma, Michael G. Gardiner, Martin G. Banwell, Maria da C. F. de Oliveira, Manoel O. de Moraes, Claudia do Ó Pessoa
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.