PubMed Health⌕ Search

Biomedical subjects

D W Boykin

Publications and source records attributed to D W Boykin.

At least 19 recordsLinked to original sources
PubMed1991

Intercalation binding of 6-substituted naphthothiopheneamides to DNA: enthalpy and entropy components.

N-(3-dimethylaminopropyl)naphtho[2,1-b]thiophene-4-carboxamide and the 6-substituted methoxy, methyl, fluoro, chloro, bromo, trifluoromethyl, and cyano derivatives have been shown to bind to DNA via intercalation with binding constants in the 35-900 X 10(3) range at 25 degrees C, pH 7, and [Na+] = 0.019M. Both electron-donating and -withdrawing substituents enhance intercalation binding, but the binding affinity is most enhanced by the cyano substituent. Calorimetric titrations for calf thymus DNA differ dramatically from those reported for ethidium [Hopkins et al. (1990) Biopolymers Vol. 29, pp. 449-459]. Apparent enthalpy parameters (delta HB) for intercalation are constant only at low coverage of sites and become much more positive as saturation is approached. In the plateau region, delta HB values for the parent and the cyano-, fluoro-, chloro-, and bromo-substituted compounds are nearly the same (approximately -5.9 kcal/mol). For the methyl- (-6.8 kcal/mol) and methoxy- (-7.5 kcal/mol) substituted compounds, the delta HB values are more exothermic than that for the unsubstituted compound, whereas delta HB for the trifluoromethyl compound is approximately 1 kcal/mol less exothermic. The corresponding delta SB values, corrected for mixing effects, are in the 7-15-cal/deg/mol range and are approximately linearly related to delta HB if the cyano derivative is excluded.

Calorimetry↗
PubMed1990

The interaction of unfused polyaromatic heterocycles with DNA: intercalation, groove-binding and bleomycin amplification.

A number of unfused-aromatic cations have been found to bind to DNA by intercalation and to amplify the bleomycin catalysed cleavage of DNA. These molecules are more similar in structure to unfused minor-groove binding compounds such as netropsin and DAPI than to fused-ring intercalators such as proflavine. An analysis of DAPI interactions with specific sequence DNA polymers has indicated that the binding modes for the molecule are sequence dependent: minor groove binding in sequences of three or more AT base pairs and intercalation in mixed or pure GC base pair sequences. As with other unfused intercalators which bind with their cationic side chains in the major groove, the amidinium groups of DAPI are in the major groove in the GC intercalation complex. DAPI is, thus, a good bleomycin amplifier in GC sequences but its minor-groove binding mode in AT sequences leads to bleomycin inhibition.

Base Sequence↗
PubMed1987

The influence of intercalator structure on DNA binding strength: the importance of side chain orientation.

A naphthothiophene intercalator with a cationic side chain linked to the ring through an ester group (1E) has been shown to bind to DNA almost an order of magnitude more strongly than a similar compound with the side chain linked to the ring through an amide group (1A) (W.D. Wilson, et al., Biophys. Chem. 24, 101-109 (1986]. X-ray crystallographic analysis of these two compounds indicates that both the ester and amide groups are essentially planar but that the amide is twisted approximately 30 degrees out of the aromatic plane of the naphthothiophene while the ester and ring system are co-planar. Proton NMR studies of the DNA complexes of these two compounds indicate that the naphthothiophene ring is intercalated in both 1A and 1E but that the protons of the ring system near the side chain interact with DNA base pairs at the binding site significantly better in 1E than in 1A. The protons next to the ester group on the side chain of 1E are also shifted upfield significantly more on addition of DNA than those of 1A. The large planar area of 1E, thus, allows greater stacking, complex geometry optimization, and dipolar interactions of the ester group with DNA base pairs at the binding site to account for the larger binding constant of this compound relative to 1A.

Base Composition↗
PubMed1986

The effect of intercalator structure on binding strength and base-pair specificity in DNA interactions.

The interaction of naphthothiophene, phenanthrene and anthracene ring systems, which have amide and ester side chains with cationic groups (synthesized from the aromatic acid chlorides and appropriate amines and alcohols), with calf thymus DNA has been investigated by using viscometric titrations, spectrophotometric binding experiments and 1H-, 31P- and 17O-NMR methods. The viscosity and NMR experiments suggest that all of these compounds bind to DNA by intercalation. These experiments and spectrophotometric binding studies, however, indicate that there is considerable variation in the interaction of these compounds with DNA. These variations can all be explained by the geometry of the ring systems, the position of protons adjacent to the side chains, and the relative sizes of the amide and ester side chains. With the naphthothiophene ester and amide, for example, the planar amide cannot rotate into the plane of the naphthothiophene ring whereas the smaller planar ester can. With this ring system the ester has a significantly higher binding constant than the amide derivative. Additional binding studies with poly[d(A-T)2] and poly[d(G-C)2] have shown that all of these compounds bind more strongly to the A-T- than the G-C-containing polymer. Since the ester compounds do not have hydrogen bond donating groups proximate to the aromatic ring, these results suggest a model for the A-T specificity of these compounds that involves a solvent-mediated hydrogen bond between the C-2 carbonyl of thymine and the carbonyl group of the intercalators.

Animals↗
PubMed1985

The intercalation of 6-chloro-substituted-9-[[3-(dimethylamino)propyl]amino]acridines with DNA.

A series of 6-chloro-2-substituted-9-[[3-(dimethylamino)propyl]amino]acridines has been prepared. The binding affinities and the unwinding angles for the acridine derivatives, relative to ethidium, were determined from viscometric titrations with ccs-DNA. The binding affinities were the same, within experimental error, ca. 2.0 X 10(-5). Similarly, with the exception of 11, the unwinding angles were close to 17 degrees. For 11 the unwinding angle (12 degrees) was smaller than the other derivatives. The general insensitivity of the apparent binding constants to substituent effects is attributable to a masking effect of the formal charge on the ring. The smaller unwinding angle for 11 is believed to arise from its relative dissymmetry, resulting in a "wedge" effect upon intercalation.

Aminoacridines↗
PubMed1979

Phenazines with two cationic side chains as potential antimalarials.

1,9-Phenazine-bis(dialkylaminocarboxamides) were prepared for screening as potential antimalarials. No significant activity against Plasmodium berghei was observed. The phenazine targets were prepared from 1,9-phenazinedicarboxylic acid by standard methods. The reaction between 1,9-phenazinedicarboxylic acid and thionyl chloride in the presence of dimethylformamide unexpectedly gave 4-chloro-1,9-phenazinedicarbonyl chloride.

Animals↗
PubMed1978

Synthesis of as-triazines as potential antiviral agents.

Four acenaphtho[1,2-e]-as-triazines and 11 5,6-diaryl-as-triazines, all substituted with an aliphatic or aromatic amino function in the 3-position, were synthesized. Two acenaphthotriazines were active against vesicular stomatitis virus in tissue culture.

Animals↗
PubMed1977

Synthesis and antiprotozoal activity of 2,5-bis(4-guanylphenyl)furans.

Eighteen substituted 2,5-bis(4-guanylphenyl)furans and related analogues, including "masked" amidines in which the guanyl function is incorporated into a heterocyclic ring, have been synthesized and their antimalarial and antitrypanosomal activity has been evaluated. None of the compounds exhibited high orders of antimalarial activity; however, 11 were very active against Trypanosoma rhodesiense in mice. Six compounds, including 2,5-bis(4-guanylphenyl)furan (4) and its 3-chloro (32), 3,4-dichloro (31), 3-methyl (25), 3,4-dimethyl (20), and 3-chloro-4-methyl (38) derivatives, produced cures in mice at submilligram dosage levels; the 3,4-dimethyl (20) analogue exhibited a prolonged curative effect providing protection for 30 days after a single dose against a challenge by T. rhodesiense. These six compounds are somewhat more active in this screen than stilbamidine, hydroxystilbamidine, and pentamidine. The "masked" amidines generally exhibited lower antitrypanosomal activity than their true guanyl counterparts. Compound 4 was synthesized from 1,4-di-p-bromophenyl-1,4-butanedione by cyclodehydrative furanization to 2,5-bis(4-bromophenyl)furan (2) which was allowed to react with Cu2(CN)2 to produce the corresponding bis-nitrile 3. The latter compound was ultimately converted by way of an imidate ester into 4. Similarly, the 3- and/or 4-substituted derivatives of 2 were employed to prepare the other members of the series.

Animals↗
PubMed1975

Complex formation between naphthothiopheneethanolamines and deoxyribonucleic acids.

Reduced viscosities, viscometric titrations, fluorescence, and flow dichroism measurements indicate that the aromatic ring system of naphthothiopheneethanolamines (NA) is intercalated on binding to DNA. No marked change in binding was found on substituting a dibutylamino group for a piperidyl ring on the side chain. Ionic strength studies, however, did indicate that the positive charge on the side chain is quite important for binding. Both the binding equilibrium constant and the number of binding sites, as determined from a Scatchard plot of spectrophotometric results, decreased on increasing the sodium chloride concentration. The increase in Tm for several DNA samples, caused by adding NA to DNA at a fixed ratio, showed a marked dependence on the percentage of AT base pairs. The conclusion drawn from these data is that the DNA-NA complex involves high specificity of the NA for AT base pairs, intercalation of the aromatic ring system, and binding of the NA side chain in the DNA minor groove with strong interaction between the positively charged side chain and the DNA phosphate groups.

Antimalarials↗