%0 Journal Article %1 WOS:000541747800032 %A Farias, Kaio %A da Costa, Roner F %A Meira, Assuero S %A Diniz-Filho, Jairo %A Bezerra, Eveline M %A Freire, Valder N %A Guest, Prue %A Nikahd, Maryam %A Ma, Xinghua %A Gardiner, Michael G %A Banwell, Martin G %A da Oliveira, Maria C F %A Moraes, Manoel O %A de Pessoa, Claudia O %C 1155 16TH ST, NW, WASHINGTON, DC 20036 USA %D 2020 %I AMER CHEMICAL SOC %J ACS MEDICINAL CHEMISTRY LETTERS %K Eg5; OVCAR-8 agents; cell-line; docking; molecular pterocarpan} {Anticancer %N 6 %P 1274-1280 %R 10.1021/acsmedchemlett.0c00097 %T Antitumor Potential of the Isoflavonoids (+)- and (-)-2,3,9-Trimethoxypterocarpan: Mechanism-of-Action Studies %V 11 %X 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.

@article{WOS:000541747800032, 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.}, added-at = {2022-05-23T20:00:14.000+0200}, address = {1155 16TH ST, NW, WASHINGTON, DC 20036 USA}, author = {Farias, Kaio and da Costa, Roner F and Meira, Assuero S and Diniz-Filho, Jairo and Bezerra, Eveline M and Freire, Valder N and Guest, Prue and Nikahd, Maryam and Ma, Xinghua and Gardiner, Michael G and Banwell, Martin G and da Oliveira, Maria C F and Moraes, Manoel O and de Pessoa, Claudia O}, biburl = {https://www.bibsonomy.org/bibtex/299f2e3ad83a13f79767ae4c06b64b8c4/ppgfis_ufc_br}, doi = {10.1021/acsmedchemlett.0c00097}, interhash = {dffa430c0cda38248e469cdb5d5f20db}, intrahash = {99f2e3ad83a13f79767ae4c06b64b8c4}, issn = {1948-5875}, journal = {ACS MEDICINAL CHEMISTRY LETTERS}, keywords = {Eg5; OVCAR-8 agents; cell-line; docking; molecular pterocarpan} {Anticancer}, number = 6, pages = {1274-1280}, publisher = {AMER CHEMICAL SOC}, pubstate = {published}, timestamp = {2022-05-23T20:00:14.000+0200}, title = {Antitumor Potential of the Isoflavonoids (+)- and (-)-2,3,9-Trimethoxypterocarpan: Mechanism-of-Action Studies}, tppubtype = {article}, volume = 11, year = 2020 }