Bozenna Golankiewicz

Aqueous solubilities, infinite dilution activity coefficients and octanol-water partition coefficients of tricyclic analogs of acyclovir

AbstractSolubilities of tricyclic analogs of acyclovir have been determined in water at 25, 35, and 45°C and in octanol, water-saturated octanol, and octanol-saturated water at 25°C. Octanol-water partition coefficients were determined at 25°C. Melting temperatures and molar enthalpies of fusion were measured. Activity coefficients in water, octanol, and in aqueous octanol solutions were determined and are discussed. The effect of hydrophilic and hydrophobic substituents in the tricyclic analogs on their thermodynamic properties are discussed. The standard Gibbs energy of transfer between the saturated phases were found to correlate with known values of the melting point of the solvents and the solubilities of the solute. For a number of the compounds examined, correlations between the minimum inhibitory concentration against the herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), thymidine kinase-deficient (TK−) strains of VZV and

Pronounced cytostatic activity and bystander effect of a novel series of fluorescent tricyclic acyclovir and ganciclovir derivatives in herpes simplex virus thymidine kinase gene-transduced tumor cell lines.

\Delta G_{{\text{W}} \to {\text{0}}}^0 ;\Delta G_{{\text{tr}}}^0

A CASE OF UNUSUAL STERICALLY DRIVEN C-TRITYLATION REACTION OF TRICYCLIC ANALOGUES OF ACYCLOVIR

were established. Detailed conclusions have been derived concerning the relationships between the structure and the thermodynamic parameters of the compounds examined.

Synthesis and Fluorescent Properties of 6-(4-Biphenylyl)-3,9-dihydro-9-oxo-5H-imidazo[1,2-A]purine Analogues of Acyclovir and Ganciclovir

Abstract A novel transpurination reaction of tetraacetylguanosine was successfully applied for the preparation of 9-(2-hydroxyethoxymethyl)-and 9-(1,3-dihydroxy-2-propoxymethyl)guanines (compounds 1 and 2, respectively). Yield of the desired 9-isomers was significantly increased by application of the thermal 7=9 transglycosylation.

Synthesis of acyclowyosine and acyclo-3-methylguanosine, as probes for some chemical and biological properties resulting from the N-3 substitution of guanosine and its analogues

A number of tricyclic acyclovir (ACV) and ganciclovir (GCV) derivatives substituted with bulky lipophilic groups have been identified as potent and highly selective cytostatic agents against herpes simplex virus type 1 (HSV-1)-thymidine kinase (TK) gene-transduced human osteosarcoma and murine mammary carcinoma tumor cells. Although their affinity for HSV-1 TK was inferior to that of ACV or GCV, their cytostatic potency and selectivity was at least as high as observed for the parental ACV and GCV compounds. The tricyclic ACV and GCV derivatives were also endowed with a very pronounced bystander effect in cell culture, albeit at relatively high drug concentrations. Unlike ACV and GCV, the tricyclic purine derivatives are endowed with intrinsically strong fluorescent properties, which allow simple and sensitive monitoring of drug concentrations in biological fluids and tissues. Also, the lipophilicity of the tricyclic purine derivatives is much higher than that of ACV and GCV, and this may allow better uptake of these derivatives from the blood into the central nervous system.

Spectral and photophysical properties of some imidazo[1,2-a]purine derivatives related to acyclovir

Abstract Tetraacetylguanosine was converted into fully acetylated derivatives of acyclovir and 9-β-D-xylofuranosyl guanine in a novel transglyco-sylation reaction

Water molecules in the crystal structure of tricyclic acyclovir

Abstract 3,9-Dihydro-3-[(2-hydroxyethoxy)methyl]-6-methyl-9-oxo-5 H -imidazo[1,2- a ]purine ( 1 ) and its silylated derivative ( 2 ) when tritylated under conditions suitable for regioselective N-5 alkylation underwent instead C-substitution to give 7-trityl ( 12, 3 ) and 7-(4-benzhydrylphenyl) ( 13, 4 ) derivatives as major and minor products, respectively. Substrates lacking 6-Me group ( 5, 6 ) yielded 5-tritylated ( 10, 7 ) and 5,7-ditritylated ( 11, 8 ) major products and 7-tritylated ( 9 ) minor product. The regioselectivity of the reaction seems to be driven mainly by steric hindrance of the 6-Me substituent.

Substituent — Directed Aralkylation and Alkylation Reactions of the Tricyclic Analogues of Acyclovir and Guanosine

Abstract Tricyclic (T) analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) carrying the 3,9-dihydro-9-oxo-5H-imidazo[1,2-a]purine system [i.e., 6-(4-BrPh)TACV, 5 and 6-(4-BrPh)TGCV, 6] were transformed into 6-[(4′-R2)-4-biphenylyl] derivatives of TACV (7–9) and TGCV (10–12) by Suzuki cross coupling with 4-substituted phenylboronic acids. Compound 11 (R2 = CH2OH) showed a high (∼1000) selectivity index against herpes simplex virus type 1 (HSV-1) together with advantageous fluorescence properties (emission in visible region, little overlap with absorption and moderate intensity).