- Electrospray-ionization mass spectrometry study of cyclodextrin complexes with A007 prodrugs
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Electrospray-ionization mass spectrometric (ESIMS) studies of several A007 prodrugs in aqueous cyclomaltohexaose (α-cyclodextrin, α-CD), cyclomaltoheptaose (β-cyclodextrin, β-CD), and cyclomaltooctaose (γ-cyclodextrin, γ-CD) were performed. The acetic aci
- SagiRaju, Sarada,Chen, Kan,Cole, Richard B.,Jursic, Branko S.
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- Design, synthesis, and anticancer properties of 4,4′ -dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues
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4,4′-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 102-103 when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.
- Morgan, Lee Roy,Thangaraj, Kanappan,LeBlanc, Blaise,Rodgers, Andrew,Wolford, Lionel T.,Hooper, Catherine L.,Fan, Dominic,Jursic, Branko S.
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p. 4552 - 4563
(2007/10/03)
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