A series of nitrogen mustard analogues of the DNA minor groove binding fluorophore pibenzimol (Ho... more A series of nitrogen mustard analogues of the DNA minor groove binding fluorophore pibenzimol (Hoechst 33258) have been synthesized and evaluated for antitumor activity. Conventional construction of the bisbenzimidazole ring system from the piperazinyl terminus, via two consecutive Pinner-type reactions, gave low yields of products contaminated with the 2-methyl analogue which proved difficult to separate. An alternative synthesis was developed, involving construction of the bisbenzimidazole from the mustard terminus, via Cu(2+)-promoted oxidative coupling of the mustard aldehydes with 3,4-diaminobenzonitrile to form the monobenzimidazoles, followed by a Pinner-type reaction and condensation with 4-(1-methyl-4-piperazinyl)-o-phenylenediamine. This process gives higher yields and pure products. The mustard analogues showed high hypersensitivity factors (IC50AA8/IC50 UV4), typical of DNA alkylating agents. There was a large increase in cytotoxicity (85-fold) across the homologous series which cannot be explained entirely by changes in mustard reactivity and may be related to altering orientation of the mustard with respect to the DNA resulting in different patterns of alkylation. Pibenzimol itself (which has been evaluated clinically as an anticancer drug) was inactive against P388 in vivo using a single-dose protocol, but the short-chain mustard homologues were highly effective, eliciting a proportion of long-term survivors.
... THF, 109-99-9. Oxidation of Vicinal Diols to a-Dicarbonyl Compounds by Trifluoroacetic Anhydr... more ... THF, 109-99-9. Oxidation of Vicinal Diols to a-Dicarbonyl Compounds by Trifluoroacetic Anhydride "Activated" Dimethyl Sulfoxide Catherine M. Amon, Martin G. Banwell,*l and G. Lance Gravatt Department of Chemistry, The ...
Journal of The Chemical Society-perkin Transactions 2, 1991
Rate constants for the hydrolysis of a series of aromatic nitrogen mustards Ar–X–C 6 H 4-N (CH 2 ... more Rate constants for the hydrolysis of a series of aromatic nitrogen mustards Ar–X–C 6 H 4-N (CH 2 CH 2 Cl) 2 (X= O, CH 2, CONH, S, CO and SO 2) in buffered aqueous acetone mixtures have been obtained using an HPLC technique which allows evaluation of the ...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of The Chemical Society-perkin Transactions 1, 1993
... J. Chem., 1992, 45, 1967 ; MG Banwell, SC Peters, RJ Greenwood, MF Mackay, E. Hamel and CM Li... more ... J. Chem., 1992, 45, 1967 ; MG Banwell, SC Peters, RJ Greenwood, MF Mackay, E. Hamel and CM Lin, Aust. J. Chem., 1992, 45, 1577 CAS ; MG Banwell, JM Cameron, MP Collis, GT Crisp, RW Gable, E. Hamel, JN Lambert, MF Mackay, ME Reum and JA Scoble, Aust. ...
A series of nitrogen mustard analogues of the DNA minor groove binding fluorophore pibenzimol (Ho... more A series of nitrogen mustard analogues of the DNA minor groove binding fluorophore pibenzimol (Hoechst 33258) have been synthesized and evaluated for antitumor activity. Conventional construction of the bisbenzimidazole ring system from the piperazinyl terminus, via two consecutive Pinner-type reactions, gave low yields of products contaminated with the 2-methyl analogue which proved difficult to separate. An alternative synthesis was developed, involving construction of the bisbenzimidazole from the mustard terminus, via Cu(2+)-promoted oxidative coupling of the mustard aldehydes with 3,4-diaminobenzonitrile to form the monobenzimidazoles, followed by a Pinner-type reaction and condensation with 4-(1-methyl-4-piperazinyl)-o-phenylenediamine. This process gives higher yields and pure products. The mustard analogues showed high hypersensitivity factors (IC50AA8/IC50 UV4), typical of DNA alkylating agents. There was a large increase in cytotoxicity (85-fold) across the homologous series which cannot be explained entirely by changes in mustard reactivity and may be related to altering orientation of the mustard with respect to the DNA resulting in different patterns of alkylation. Pibenzimol itself (which has been evaluated clinically as an anticancer drug) was inactive against P388 in vivo using a single-dose protocol, but the short-chain mustard homologues were highly effective, eliciting a proportion of long-term survivors.
... THF, 109-99-9. Oxidation of Vicinal Diols to a-Dicarbonyl Compounds by Trifluoroacetic Anhydr... more ... THF, 109-99-9. Oxidation of Vicinal Diols to a-Dicarbonyl Compounds by Trifluoroacetic Anhydride "Activated" Dimethyl Sulfoxide Catherine M. Amon, Martin G. Banwell,*l and G. Lance Gravatt Department of Chemistry, The ...
Journal of The Chemical Society-perkin Transactions 2, 1991
Rate constants for the hydrolysis of a series of aromatic nitrogen mustards Ar–X–C 6 H 4-N (CH 2 ... more Rate constants for the hydrolysis of a series of aromatic nitrogen mustards Ar–X–C 6 H 4-N (CH 2 CH 2 Cl) 2 (X= O, CH 2, CONH, S, CO and SO 2) in buffered aqueous acetone mixtures have been obtained using an HPLC technique which allows evaluation of the ...
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Journal of The Chemical Society-perkin Transactions 1, 1993
... J. Chem., 1992, 45, 1967 ; MG Banwell, SC Peters, RJ Greenwood, MF Mackay, E. Hamel and CM Li... more ... J. Chem., 1992, 45, 1967 ; MG Banwell, SC Peters, RJ Greenwood, MF Mackay, E. Hamel and CM Lin, Aust. J. Chem., 1992, 45, 1577 CAS ; MG Banwell, JM Cameron, MP Collis, GT Crisp, RW Gable, E. Hamel, JN Lambert, MF Mackay, ME Reum and JA Scoble, Aust. ...
Uploads