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Biomedical subjects

D W Henry

Publications and source records attributed to D W Henry.

At least 37 records · Page 2Linked to original sources
PubMed1978

Antitumor anthracycline antibiotics. Structure-activity and structure-cardiotoxicity relationships of rubidazone analogues.

A series of rubidazone analogues (4-14) with varying phenyl group substituents was prepared. The effect of these compounds on inhibition of nucleic acid synthesis in cultured cells, on in vivo antitumor properties, and on cardiotoxicity was examined. Substituent effects on drug-DNA binding as indicated by DNA melting temperature measurements were also investigated. Substituent effects were essentially absent among the rubidazone analogues in in vivo and in vitro test systems which measure cytotoxic characteristics; however, the rubidazone analogues varied substantially in their cardiotoxic effects and this variation was closely correlated with the electronic character of the phenyl substituent.

Animals↗
PubMed1977

Potential antitumor agents. Some sulfur-substituted derivatives of alpha- and beta-2'-deoxythioguanosine.

A series of ten S-substituted derivatives of the alpha and beta anomers (1a and 1b) of 2'-deoxy-6-thioguanosine has been prepared by S-alkylation of the parent nucleosides and/or by mercaptide displacement reactions on 6-chloro intermediates. Against L1210 murine leukemia all beta anomers were active but potency was reduced relative to 1b. Most S-alkyl alpha anomers were inactive in this test. Limited testing against P388 murine leukemia showed all alpha-anomer derivatives to be inactive but the beta anomers were more effective than the parent. S-Substitution sharply reduced acute toxicity in both series. In vitro DNA and RNA synthesis inhibition data are also reported. The antitumor activity of these derivatives and of the 2',5'-di-O-acetyl derivatives of 1a and 1b against lymphoid leukemia L1210 is reported. Some results with the lymphocytic leukemia P388 and an in vitro assay of the inhibition of nucleic acid synthesis are also given.

Animals↗
PubMed1977

2-Deaminoactinomycin D, synthesis and interaction with deoxyribonucleic acid.

2-Deaminoactinomycin D has been synthesized and characterized. It binds to DNA by intercalation according to NMR, CD, thermal denaturation, and unwinding studies on the drug-DNA complex. Loss of the 2-amino group does not seriously affect binding parameters relative to actinomycin D; affinity for calf thymus DNA may even be increased, according to deltaTm measurements. The unwinding of circular DNA caused by this compound is at least as large as that effected by actinomycin D and ethidium bromide. Nevertheless, 2-deaminoactinomycin D is less effective than actinomycin D in inhibiting nucleic acid syntheses in L1210 cell culture and in in vivo antitumor activity against P388 leukemia.

Animals↗
PubMed1977

Antifilarial agents. 3-Aminopyrrolidine and 1,4-diazabicyclo[3.2.1]octane derivatives as analogues of diethylcarbamazine.

3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like antifilarial activity does not require that both pharmacophores be incorporated into one ring. Results with the 1,4-diazabicyclo[3.2.1]octanes establish that an axial conformation of the alkyl substituent corresponding to the equatorial N-methyl group of diethylcarbamazine is fully consistent with high activity. Other conformational consideration pertinent to DEC analogues are discussed.

Animals↗
PubMed1976

Adriamycin analogs. Periodate oxidation of adriamycin.

Adriamycin is selectively cleaved in high yield at the C13-C14 bond by 1 equiv of sodium metaperiodate to yield carboxylic acid 3. The corresponding methyl ester 4 is obtained by Fischer esterification. Spectral studies indicate that 3 and 4 bind to calf thymus DNA in a manner similar to adriamycin and daunomycin but Tm measurements suggest that less stable complexes are formed. Ester 4 inhibits DNA and RNA synthesis in cultured L1210 cells at levels comparable to adriamycin but acid 3 is much less effective. Both new compounds are moderately effective as antitumor agents against P388 lymphocytic leukemia in the mouse.

Animals↗