Metal-dependent thermal stability of recombinant endo-mannanase (ManB-1601) belonging to family GH 26 from Bacillus sp. CFR1601

A GH 26 endo-mannanase from Bacillus sp. CFR1601 was purified to homogeneity (M_w ∼39 kDa, specific activity 10,461.5 ± 100 IU/mg). Endo-mannanase gene (manb-1601, 1083 bp, accession No. KM404299) was expressed in Escherichia coli BL21 (DE3) and showed typical fingerprints of α/β proteins in the far-UV CD. A high degree of conservation among amino acid residues involved in metal chelation (His-1, 23 and Glu-336) and internal repeats (122–152 and 181–212) was observed in endo-mannanases reported from various Bacillus sp. Thermal inactivation kinetics suggested that metal ions are quintessential for stabilization of ManB-1601 structure as holoenzyme (E_a 87.4 kcal/mol, ΔH 86.7 kcal/mol, ΔS 186.6 cal/k/mol) displayed better values of thermodynamic parameters compared to metal-depleted ManB-1601 (E_a 47 kcal/mol, ΔH 45.7 kcal/mol, ΔS 64.7 cal/k/mol). EDTA treatment of ManB-1601 not only lead to transitions in both secondary and tertiary structure but also promulgated the population of conformational state that unfolds at lower temperature. ManB-1601 followed a three-state process for thermal inactivation wherein loss of tertiary structure preceded the concurrent loss of secondary structure and activity.     

Synthesis and characterization of novel 1,2-oxazine-based small molecules that targets acetylcholinesterase

Thirteen 2-oxazine-based small molecules were synthesized targeting 5-lipoxygenase (LOX), and acetylcholinesterase (AChE). The test revealed that the newly synthesized compounds had potent inhibition towards both 5-LOX and AChE in lower micro molar concentration. Among the tested compounds, the most active compound, 2-[(2-acetyl-6,6-dimethyl-4-phenyl-5,6-dihydro-2H-1,2-oxazin-3-yl)methyl]-1H-isoindole-1,3(2H)-dione (2a) showed inhibitory activity towards 5-LOX and AChE with an IC₅₀ values of 1.88, and 2.5 μM, respectively. Further, the in silico molecular docking studies revealed that the compound 2a bound to the catalytic domain of AChE strongly with a highest CDOCKER score of −1.18 kcal/mol when compared to other compounds of the same series. Additionally, 2a showed a good lipophilicity (log P = 2.66), suggesting a potential ability to penetrate the blood–brain-barrier. These initial pharmacological data revealed that the compound 2a could serve as a drug-seed in developing anti-Alzheimer’s agents.     

Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)

Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed) and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via secoisolariciresinol (6) and glucosyl donor 7 through a concise route that involved chromatographic separation of diastereomeric diglucoside derivatives (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent antioxidant properties (EC₅₀ = 292.17 ± 27.71 μM and 331.94 ± 21.21 μM, respectively), which compared well with that of natural (S,S)-SDG-1 (EC₅₀ = 275.24 ± 13.15 μM). These values are significantly lower than those of ascorbic acid (EC₅₀ = 1129.32 ± 88.79 μM) and α-tocopherol (EC₅₀ = 944.62 ± 148.00 μM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68 ± 0.27; synthetic (S,S)-SDG-1: 2.09 ± 0.16; synthetic (R,R)-SDG-2: 1.96 ± 0.27], peroxyl [natural (S,S)-SDG-1: 2.55 ± 0.11; synthetic (S,S)-SDG-1: 2.20 ± 0.10; synthetic (R,R)-SDG-2: 3.03 ± 0.04] and DPPH [natural (S,S)-SDG-1: EC₅₀ = 83.94 ± 2.80 μM; synthetic (S,S)-SDG-1: EC₅₀ = 157.54 ± 21.30 μM; synthetic (R,R)-SDG-2: EC₅₀ = 123.63 ± 8.67 μM] radicals. These results confirm previous studies with naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as potent antioxidants and free radical scavengers for potential in vivo use.     

A new synthesis and an antiviral assessment of the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin

A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC₅₀ of 1.2 μg/mL in the neutral red assay and 14 μg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21–36 μg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4′,4′-difluoro analog of 3 (that is, 2).     

Nitrite correlates with 3-nitrotyrosine but not with the F2-isoprostane 15(S)-8-iso-PGF2α in urine of rheumatic patients

In vitro studies suggested that nitrite may play a cytoprotective role in inflammation. The aim of the present clinical study was to investigate the relationship between the NO metabolites nitrite and nitrate and the biomarkers of oxidative stress 3-nitrotyrosine (3-NT) and 15(S)-iso-PGF_2α in patients suffering from chronic inflammatory rheumatic diseases. In morning urine from 28 patients with different chronic inflammatory rheumatic diseases (23–82 years of age) and from 41 healthy persons of both genders, nitrite and nitrate were quantitated by GC-MS, and 3-NT and 15(S)-iso-PGF_2α by GC-MS/MS. Mean creatinine-corrected urinary excretion rates of nitrite (1.1 versus 0.19 μmol/mmol, P = 0.00012) and 3-NT (1.2 versus 0.39 nmol/mmol, P = 0.01629), but not of nitrate (105 versus 106 μmol/mmol), were significantly elevated in rheumatism as compared to health. Urinary excretion rate of 15(S)-iso-PGF_2α did not differ between patients and healthy subjects (65 versus 69 pmol/mmol creatinine, P = 0.48). In rheumatism, urinary 3-NT correlated closely with nitrite (R = 0.788, P < 0.0001) and moderately with nitrate (R = 0.45, P < 0.016), but did not correlate with 15(S)-iso-PGF_2α (R = ?0.083, P = 0.68). In healthy persons there was no correlation between urinary 3-NT and nitrite or nitrate. Our study suggests that urinary nitrite may represent a novel specific biomarker of nitrative stress in chronic inflammatory rheumatic disease. In another eight patients with chronic inflammatory rheumatic diseases we found higher nitrite concentrations in synovial fluid as compared to serum (1.30 versus 0.35 μM). We hypothesize that in chronic inflammatory rheumatic diseases nitrite concentration is elevated in the inflamed joint and contributes to the inactivation of myeloperoxidase-catalyzed production of hypochloric acid by forming nitryl chloride which eventually nitrates tyrosine to form 3-NT.     

Conformational analysis of perezone and dihydroperezone using vibrational circular dichroism

The vibrational circular dichroism (VCD) spectra of perezone and dihydroperezone measured from CDCl₃ solutions were quite similar, suggesting analogous conformations for both molecules. Their absolute configurations were confirmed by comparison of the experimental VCD spectrum of each compound with curves generated from theoretical calculations using density functional theory (DFT) at the B3LYP/DGDZVP level of theory taking into account their conformational mobility. Conformational analysis of the 8-(R) enantiomer showed 19 low energy conformers in a 2.4 kcal/mol energy range, while for 8-(R), with the saturated side alkyl chain, 34 conformers were considered in the first 2 kcal/mol. Initial analyses were carried out using a Monte Carlo searching with the MMFF94 molecular mechanics force field, all MMFF94 conformers were geometrically optimized using DFT at the B3LYP/6-31G(d) level of theory, followed by reoptimization and calculations of their vibrational frequencies at the B3LYP/DGDZVP level. Good agreement between the theoretical 8-(R) enantiomers and experimental VCD curves were observed for both.     

Gynostemosides A–E,megastigmane glycosides from Gynostemma pentaphyllum

Megastigmane glycosides (1–5) together with seven (6–12) related known compounds were isolated from the whole plants of Gynostemma pentaphyllum. The structures were elucidated by means of spectroscopic methods, including 2D NMR, HR-ESIMS, and circular dichroism (CD), as well as chemical transformations to be (3R, 4R, 5S, 6S, 7E)-3,4,6-trihydroxymegastigmane-7-en-9-one-3-O-β-d-glucopyranoside (gynostemoside A, 1), (3S, 4S, 5R, 6R, 7E, 9R)-3,4,6,9-tetrahydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside B, 2), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-9-O-β-d-glucopyranoside (gynostemoside C, 3), (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-3-O-β-d-glucopyranoside (gynostemoside D, 4), and (3S, 4S, 5S, 6S, 7E, 9R)-3,4,9-trihydroxymegastigmane-7-en-4-O-β-d-glucopyranoside (gynostemoside E, 5), respectively.     

Discovery of a new series of monoamine reuptake inhibitors,the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols

A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols, have been discovered by combining virtual and focused screening efforts with design techniques. Synthesis of the two diastereomeric isomers of the molecule followed by chiral resolution of each enantiomer revealed the (2R,3S)-isomer to be a potent norepinephrine reuptake inhibitor (IC₅₀ = 28 nM) with excellent selectivity over the dopamine transporter and 13-fold selectivity over the serotonin transporter.     

Isoform-selective inhibition of chrysin towards human cytochrome P450 1A2. Kinetics analysis,molecular docking,and molecular dynamics simulations

Our kinetics studies demonstrated that the nature product chrysin exhibited a high inhibitory affinity of 54 nM towards human cytochrome P450 1A2 and was comparable to α-naphthoflavone (49 nM), whereas it represented a moderate affinity of 5225 nM against human cytochrome P450 2C9. However, it remains unclear how this inhibitor selectively binds 1A2. To better understand the isoform selectivity of chrysin, molecular docking and molecular dynamics simulations were performed. Chrysin formed a strong H-bond with Asp313 of 1A2. The stacking interactions with Phe226 also contributed to its tight binding to 1A2. The larger and much more open active site architectures of 2C9 may explain the weaker inhibitory affinity of chrysin towards 2C9. The predicted binding free energies suggest that chrysin preferred 1A2 (ΔG_{bind, pred} = ?23.11 kcal/mol) to 2C9 (?20.41 kcal/mol). Additionally, the present work revealed that 7-hydroxy-flavone bound to 1A2 in a similar pattern as chrysin and represented a slightly less negative predicted binding free energy, which was further validated by our kinetics analysis (IC₅₀ = 240 nM). Results of the study can provide insight for designing novel isoform-selective 1A2 inhibitors.     

Enantioselective synthesis of (S)-phenylephrine by whole cells of recombinant Escherichia coli expressing the amino alcohol dehydrogenase gene from Rhodococcus erythropolis BCRC 10909

(R)-phenylephrine [(R)-PE] is an α₁-adrenergic receptor agonist that is widely used in over-the-counter drugs to treat the common cold. We found that Rhodococcus erythropolis BCRC 10909 can convert detectable level of 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) to (S)-PE by high performance liquid chromatography tandem mass spectrometry analysis. An amino alcohol dehydrogenase gene (RE_AADH) which possesses the ability to convert HPMAE to (S)-PE was then isolated from R. erythropolis BCRC 10909 and expressed in Escherichia coli NovaBlue. The purified RE_AADH, tagged with 6×His, had a molecular mass of approximately 30 kDa and exhibited a specific activity of 0.19 μU/mg to HPMAE in the presence of NADPH, indicating this enzyme could be categorized as NADP⁺-dependent short-chain dehydrogenase reductase. E. coli NovaBlue cell expressing the RE_AADH gene was able to convert HPMAE to (S)-PE with more than 99% enantiomeric excess (ee), 78% yield and a productivity of 3.9 mmol (S)-PE/L h in 12 h at 30 °C and pH 7. The (S)-PE, recovered from reaction mixture by precipitation at pH 11.3, could be converted to (R)-PE (ee > 99%) by Walden inversion reaction. This is the first reported biocatalytic process for the production of (S)-PE from HPMAE.     

Enantioselective synthesis of (S)-phenylephrine by recombinant Escherichia coli cells expressing the short-chain dehydrogenase/reductase gene from Serratia quinivorans BCRC 14811

BackgroundAn amino alcohol dehydrogenase gene (RE_AADH) from Rhodococcus erythropolis BCRC 10909 has been used for the conversion of 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) to (S)-phenylephrine [(S)-PE]. However RE_AADH uses NADPH as cofactor, and only limited production of (S)-PE from HPMAE is achieved.MethodsA short-chain dehydrogenase/reductase gene (SQ_SDR) from Serratia quinivorans BCRC 14811 was expressed in Escherichia coli BL21 (DE3) for the conversion of HPMAE to (S)-PE.ResultsThe SQ_SDR enzyme was capable of converting HPMAE to (S)-PE in the presence of NADH and NADPH, with specific activities of 26.5 ± 2.3 U/mg protein and 0.24 ± 0.01 U/mg protein, respectively, at 30 °C and at a pH of 7.0. The E. coli BL21 (DE3), expressing NADH-preferring SQ_SDR, converted HPMAE to (S)-PE with more than 99% enantiomeric excess, a conversion yield of 86.6% and a productivity of 20.2 mmol/l h, which was much higher than our previous report using E. coli NovaBlue expressing NADPH-dependent RE_AADH as the biocatalyst.ConclusionThe SQ_SDR enzyme with its high catalytic activity and strong preference for NADH as a cofactor provided a significant advantage in bioreduction.     

A two-step enzymatic resolution of glycidyl butyrate

A two-step enzymatic resolution process for production of (R)- and (S)-glycidyl butyrate was investigated and the lipases were screened. The first step involved a hydrolysis of (R,S)-glycidyl butyrate catalyzed by porcine pancreatic lipase (S-favored) with an E of 21 for production of (R)-glycidyl butyrate (13.2 mmol, 98% ee, 36% yield) under the optimal conditions (pH 7.4, 30 °C, 30 mg/ml CTAB). Then, the recovered (R)-enriched glycidol (19.8 mmol, 65% ee, 56% yield) was used for transesterification catalyzed by Novozym 435 (R-favored) with an E of 69 to obtain (S)-glycidyl butyrate (15.1 mmol, 98% ee, 42% yield) under the optimum conditions (a_W = 0.24, n-heptane, 80 min).     

New γ-pyranone and nucleoside derivatives from Penicillium sp.

Peniopyranone (1) and 2-methoxyl-β-l-Arabinofuroside uracil (2), together with six known compounds were isolated from the broth of Penicillium sp. (NO. 64). And their structures were established by comprehensive analysis of NMR, MS and CD spectra, the absolute configurations of Peniopyranone (1) were determined as 7S, 8S and 9R by calculating its ECD. The eight obtained metabolites were subjected to evaluate the preliminary cytotoxic activities to four cancer cell lines, but they showed no significant data with IC₅₀ > 50 μmol/mL. The results of acetylcholinesterase inhibiting assay showed that peniopyranone (1) displayed the inhibition activity to acetylcholinesterase with IC₅₀ at 15.2 μmol/mL.     

Trispyrazolylmethane piano stool complexes of iron(II) and cobalt(II)

A series of cationic trispyrazolylmethane complexes of the general form [Tm^RM(CH₃CN)₃]²⁺ (Tm = tris(pyrazolyl)methane, 1, R = 3,5-Me₂, M = Fe(II); 2, R = 3-Ph, M = Fe(II); 3, R = 3,5-Me₂, M = Co(II); 4, R = 3-Ph, M = Co(II)) with ‘piano-stool’ structures was prepared by the reaction of the N₃tripodal ligands (Tm^R)with [(CH₃CN)₆M](BF₄)₂ in a 1:1 stoichiometric ratio. Magnetic susceptibility measurements indicate that all four complexes with BF₄⁻ counter anions are paramagnetic, high-spin systems in the solid state with μ_eff at high temperatures of 5.2 (1, S = 2), 5.4 (2, S = 2), 4.9 (3, S = 3/2) and 4.6 (4, S = 3/2) BM, respectively. Comparisons of bond lengths from the metal centre to the Tm^R nitrogen donors, and from the metal centre to the acetonitrile nitrogen donors indicate that the neutral tripodal ligands appear to be more weakly coordinated to the metal centre than are the acetonitrile ligands. Reactions of these tripodal complexes with bidentate phosphine ligands, such as 1,2-diphosphinoethane or 1,2-bis(diallylphosphino)ethane leads to displacement of the tripodal ligand, or to the formation of more thermally stable bis-ligand complexes M(Tm^R)₂ (R = 3,5-dimethyl).     

Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo[1,2-a]pyridine symbiotic prototypes

We describe herein the design, synthesis and pharmacological evaluation of novel 3-arylamine-imidazo[1,2-a]pyridine derivatives structurally designed as novel symbiotic prototypes presenting analgesic and anti-inflammatory properties. The derivatives obtained were submitted to in vivo assays of nociception, hyperalgesia and inflammation, and to in vitro assays of human PGHS-2 inhibition. These assays allowed the identification of compound LASSBio-1135 (3a) as an anti-inflammatory and analgesic symbiotic prototype. This compound inhibited moderately the human PGHS-2 enzyme activity (IC₅₀ = 18.5 μM) and reverted the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) similarly to p38 MAPK inhibitor SB-203580 (2). Additionally, LASSBio-1135 (3a) presented activity similar to celecoxib (1) regarding the reduction of the carrageenan-induced rat paw edema (33% of inhibition at 100 μmol/kg, po). We also discovered derivatives LASSBio-1140 (3c) and LASSBio-1141 (3e) as analgesic and anti-inflammatory prototypes, which were able to attenuate the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) and reduce the carrageenan-induced paw edema (ED₅₀ = 11.5 μmol/kg (3.3 mg/kg) and 14.5 μmol/kg (4.1 mg/kg), respectively), being both more active than celecoxib (1), despite the fact that their effects involve a different mechanism of action. Additionally, derivative LASSBio-1145 (3j) showed remarkable analgesic (ED₅₀ = 22.7 μmol/kg (8.9 mg/kg)) and anti-inflammatory (ED₅₀ = 8.7 μmol/kg (3.4 mg/kg)) profile in vivo (100 μmol/kg; po), in AcOH-induced abdominal constrictions in mice and carrageenan-induced rat paw edema models, respectively, being a novel orally-active anti-inflammatory drug candidate that acts as a selective PGHS-2 inhibitor (IC₅₀ = 2.8 μM).     

Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides

With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45 °C) as the model system, the enzyme enantioselectivity in terms of V_R/V_S = 105.8 and specific activity for the fast-reacting (R)-azolide V_R/(E_t) = 0.979 mmol/(h g) were greatly improved in comparison with V_R/V_S = 8.0 and V_R/(E_t) = 0.113 mmol/(h g) of using (R,S)-naproxenyl 2,2,2-trifluoroethyl ester as the substrate. The resolution strategy was successfully extended to other (R,S)-profenyl 1,2,4-triazolides and lipases from Candida rugosa (Lipase MY) and Carica papaya (CPL) having opposite enantioselectivity to CALB. Moreover, the kinetic constants were estimated, compared with those obtained via hydrolysis, and employed for modeling time-course conversions of (R,S)-naproxenyl 1,2,4-triazolide in anhydrous MTBE. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, as well as easy product separation from the remaining substrate via reactive extraction demonstrate merits of using (R,S)-azolides but not the corresponding esters for the alcoholytic resolution.     

Anti-proliferative and computational studies of two new pregnane glycosides from Desmidorchis flava

Two new pregnane glycosides named desmiflavasides C (1) and D (2) were isolated from the sap of Desmidorchis flava (N.E.Br.) Meve & Liede and have had their structures confirmed from 1D and 2D NMR spectroscopic techniques and mass spectrometry (ESIMS). Further, the effects of desmiflavasides C (1) and D (2) on the proliferation of breast and ovarian cancer cells as well as normal breast epithelial cells in culture were examined. Interestingly, desmiflavasides C (1) and D (2) were able to cause a substantial decline in the viability of cancer cells in a concentration-dependent manner. Moreover, treatment of normal cells with compound 2 resulted in no significant growth inhibition, indicating that its cytotoxicity was selective towards cancer cells. Furthermore, the activity of compound 2 against cancer as well as normal epithelial cells was found to be similar to that of a previously reported pregnane glycoside, nizwaside (3). Molecular docking studies of desmiflavasides C (1) and D (2) and nizwaside (3) were carried out to ascertain if it was possible to predict any important binding orientations required of small molecule drug candidates with suggested protein target molecules for the purposes of being able to predict the affinity and activity to an acceptable degree by such compounds. Desmiflavaside D (2) showed a relatively good binding affinity (−22.4449 kcal/mol) as compared to the other two compounds viz., nizwaside (3) (−20.0319 kcal/mol), and desmiflavaside C (1) (−19.4042 kcal/mol). Docking results of the three pregnane glycosides viz., 1–3 revealed that these ligand molecules can accurately interact with the target protein.     

Pre-weaning growth response of lambs fed creep mixtures with varying levels of energy and protein

The pre-weaning nutrient requirements for growth of lambs were assessed by feeding them on ad libitum creep mixtures with free suckling and free choice of Pala (Z. nummularia) leaves. Thirty six lambs (15 days old) were divided into three equal groups and fed creep mixtures containing high (HEHP), medium (MEMP) and low (LELP) levels of digestible energy and protein. A cafeteria system of feeding management was used. The ratio of creep mixture, pala leaf and milk in the total DMI of HEHP lambs was 74.9:11.4:13.7. The corresponding ratios in DMI were 73.8:14.3:11.8 and 90.3:2.1:7.6 in MEMP and LELP regimens. Digestibility of DM, OM and CP was higher (P<0.01) in HEHP than MEMP and LELP. Digestibility of NDF and ADF was also significantly (P<0.01) higher in HEHP than MEMP and LELP. However, digestibility of cellulose and hemicellulose were higher (P<0.01) in LELP than other two groups. The lambs in all the three groups were in positive N balance while per cent N retention was lower (P<0.01) in LELP (52.6%) compared to MEMP (61.5%) and HEHP (70.4%). The lambs in HEHP, MEMP and LELP consumed 58.2, 51.6 and 83.5 g DM, 10.4, 7.4 and 8.0 g DCP and 250.4, 163.2 and 228.9 kcal DE/kg W^0.75/day amounting to an average of 43 g DCP/Mcal DE consumed/day and had 124, 108 and 124 g ADG, respectively. It is concluded from the study that ad libitum LELP creep mixture with free suckling and free choice pala (Z. nummularia) leaves was adequate to meet the growth requirement for 124 g pre-weaning average daily gain.     

Design,synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues

The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and for cytostatic activity against murine leukemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b exhibited antiviral activity against Influenza A H3N2 subtype (EC₅₀ = 20 μM—visual CPE score; EC₅₀ = 18 μM—MTS method; MCC >100 μM, CC₅₀ >100 μM) in Madin Darby canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular stomatitis virus and respiratory syncytial virus in HeLa cells (EC₅₀ = 9 and 12 μM, respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC₅₀ = 2.9 and 4 μM, respectively) and feline herpes virus in CRFK cells (EC₅₀ = 4 μM) but at the same time it exhibited cytotoxicity toward uninfected cell (MCC ⩾ 4 μM). Several other compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC₅₀ in the 4–50 μM range. Among them compounds (1S,2S)- and (1R,2S)-16l were the most active (IC₅₀ in the 4–7 μM range).