Urinary Schistosomiasis in Urban and Semi-Urban Communities in South-Eastern Nigeria

Background

In view of the massive rural-to-urban migration in Nigeria, investigations on transmission of urinary schistosomiasis were carried out in urban and semi-urban communities in Nike Lake area of Enugu State, Nigeria.

Methods

Urine samples of school children were tested for micro-haematuria using reagent strips followed by microscopic examination for Schistosoma haematobium eggs. Water contact sites were also identified and sampled for snails.

Results

The overall prevalence of S. haematobium eggs in school children was 4.64%. The mean intensity of infection was 1.14 ± 0.41 eggs/10ml urine. Males had insignificantly higher prevalence and intensity of S. haematobium infection than females. The youngest age group (4-7 years) had no infection. The prevalence of micro-haematuria (6.2%) was higher than that of microscopy, and this correlated positively with prevalence (r = 0.65, P < 0.01) and intensity (r = 0.50, P < 0.01) of the infection. Potential intermediate host of human shistosome collected were: Bulinus globosus, B. senegalensis and Biomphalaria pfeifferi. However, only B. globosus shed cercariae of S. haematobium, with a snail infection rate of 0.73%. Transmission was in the dry season coinciding with the drying of wells.

Conclusion

The results revealed that urinary schistosomiasis is prevalent, and that B. globosus and not B. truncatus as previously reported is the main intermediate host of urinary schistosomiasis in this part of Enugu State.     

Effect of School Based Treatment on the Prevalence of Schistosomiasis in Endemic Area in Yemen

Background

Schistosomiasis and soil transmitted infection is a major health problem of children from rural areas of developing countries including Yemen. In an attempt to reduce this burden, the Ministry of Public Health and Population in Yemen established in 2002 a programme for Schistosomal, soil transmitted infection control that aimed to reduce morbidity and prevalence rates of Schistosomiasis, and Soil transmitted helminthes to less than 5% by 2015. The study was conducted to assess the current prevalence and intensity of schistosomal infection among schoolchildren in rural areas of the Taiz governorate after 6 years of running National Control Programme.

Methods

Grade 3 schoolchildren from Shara''b Al-Raona district of Taiz Governorate were examined for infections with Schistosoma mansoni using Modified Kato–Katz method and S. haematobium applying filtration method in 1998/1999, comparing the prevalence and intensity of infection with base line study, which was done 6 years ago.

Results

The S. mansoni prevalence in the study population was 31%, while the prevalence of S. haematobium was 18.6%. This result considerably is similar to the prevalence of base line study. The intensity of mild, moderate and severe infection for S. mansoni reached to 15.9%, 60.6% & 23.5% respectively. The severity of S. haematobium infection was 68.4%. It was exceptionally found that the prevalence of S. haematobium is increased.

Conclusion

The high prevalence of schistosomiasis and low effectiveness of control programme against schistosomal infection in the study area demands consideration of alternative treatment approaches.     

Prevalence of Schistosoma intercalatum and S. haematobium Infection among Primary Schoolchildren in Capital Areas of Democratic Republic Of S?o Tomé and Príncipe,West Africa

Background

A parasitological survey of Schistosoma haematobium and S. intercalatum infection among primary schoolchildren in capital area of Democratic Republic of São Tomé and Príncipe (DRSTP) was undertaken.

Methods

Subjects with positive infection were confirmed by the detection of S. haematobium ova in the urine or S. intercalatum ova in the stool by using centrifugation concentration or merthiolate-iodine-formalin concentration method. Totally, 252 urine and stool samples, respectively, were obtained from apparently healthy schoolchildren, of which 121 from boys (9.8 ± 1.4 yr) and 131 from girls (9.7 ± 1.3 yr).

Results

None of participating schoolchildren were found having S. haematobium ova in the urinary specimen. While, among 4 primary schools studied, only schoolchildren from Saint Marçal were detected with S. intercalatum ova in the fecal specimen, making the overall prevalence of S. intercalatum infection among schoolchildren was 2.4% (6/252) and girls had insignificantly higher prevalence (3.1%, 4/131) than that (1.7%, 2/121) in boys (χ² = 0.5, P = 0.5).

Conclusion

Water control and sanitation as well as snails eliminated by molluscicides are urgently needed to reduce S. intercalatum infection in DRSTP inhabitants.     

Synthesis, evaluation and application of polycyclic fluorescent analogues as N-methyl-D-aspartate receptor and voltage gated calcium channel ligands

A series of polycyclic fluorescent ligands were synthesised and evaluated in murine striatal synaptoneurosomes for N-methyl-d-aspartate receptor (NMDAR) mediated calcium flux inhibition and inhibition of calcium influx through voltage gated calcium channels (VGCC). Amantadine (a) and N-(1-adamantyl)-1,3-propanediamine (c) substituted with 1-cyanoisoindole (3), indazole (5), dinitrobenzene (7, 8), dansyl (9, 10) and coumarin (11) moieties showed moderate to high inhibition of the NMDAR. A high degree of VGCC inhibition was observed for the cyanoisoindole compounds (3, 4) the dansyl compounds (9, 10) and the coumarin compound (12). Fluorophores conjugated to hydroxy-4-aza-8-oxoheptacyclotetradecane (13, 14) did not exhibit any significant VGCC inhibition, but the indazole conjugate (14) showed promising NMDAR activity. Dose response curves were calculated for selected NMDAR inhibitors (8-11) and N-[3-(1-adamantylamino)propyl]-5-dimethylaminonaphthalene-1-sulfonamide (10) exhibited the highest activity of the novel compounds. Compound 10 was further used as a fluorescent NMDAR ligand in a fluorescent competition assay utilizing MK-801, NGP1-01 and amantadine as known NMDAR inhibitors to demonstrate the possible applications of the novel fluorescent compounds. These small molecule fluorescent ligands can be considered as possible pharmacological tools in assay development and/or other investigations in the study of neurodegeneration.     

Synthesis and biological evaluation of some 4-functionalized-pyrazoles as antimicrobial agents

1,3-Diaryl-4-formylpyrazoles 8 bearing benzenesulfonamide moiety at position-1 were synthesized as important intermediates following Vilsmeier-Haack strategy. Aldehyde moiety of 4-formylpyrazole was then converted into carboxylic acid 9, cyano 10 and carbothioamide 11 using established procedures. Out of these 4-functionalized pyrazoles, pyrazole-4-carboxylic acids 9 and carbothioamides 11 were evaluated for their in vitro antibacterial activity against four pathogenic bacterial strains namely, Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and in vitro antifungal activity against two pathogenic fungal strains namely, Aspergillus niger and Aspergillus flavus. Three tested compounds, 9e, 11b and 11f exhibited moderate antibacterial activity against Gram-positive bacteria and 9g showed moderate antifungal activity against the tested fungi. However, none of the compounds showed any activity against Gram-negative bacteria.     

Synthesis and structure-activity relationship of 2-thiopyrimidine-4-one analogs as antimicrobial and anticancer agents

Considering that some thiopyrimidines were previously reported as potential therapeutics, the present study achieved novel analogs of bioactive 2-substituted thiopyrimidines-4-(3H)-ones via base catalyzed alkylation reaction of 2-thiouracil using alkyl and aralkyl bromides. The title compounds were 2-(1-butylthio)pyrimidine-4(3H)-one (5a), 2-(2-butylthio)pyrimidine-4(3H)-one (5b), 2-(cyclohexylmethylthio)pyrimidine-4(3H)-one (5c), 2-(benzylthio)pyrimidine-4(3H)-one (5d) and 2-(1-adamantylthio)pyrimidine-4(3H)-one (5e). Bioactivity tests revealed that thiopyrimidines 5a, 5c, 5d and 5e exhibited antimicrobial activity. The thiopyrimidine-4-one (5c) showed complete inhibition against Streptococcus pyogenes and Branhamella catarrhalis as well as antifungal action against Candida albicans. Significantly, the 1-adamantylthiopyrimidine (5e) was shown to be the most potent cytotoxic compound against multidrug-resistant small cell lung cancer (H69AR). Their structure-activity relationships were discussed.     

Synthesis and biological evaluation of unsaturated keto and exomethylene D-arabinopyranonucleoside analogs: novel 5-fluorouracil analogs that target thymidylate synthase

The synthesis of pyrimidine unsaturated keto and exomethylene arabinopyranonucleoside analogs as potential antitumor and antiviral agents is described. Commercially available 1,2,3,4-tetra-O-acetyl-d-arabinopyranose (1) was condensed with silylated thymine, uracil, 5-fluorouracil, N⁴-benzoyl cytosine and 5-(trifluoromethyl)uracil, respectively, deacetylated and acetylated to afford 1-(3,4-O-isopropylidene-α-d-arabinopyranosyl)pyrimidine analogs 4. Two different synthetic routes were investigated for the conversion of compounds 4 into the new 1-(2,3,4-trideoxy-2-methylene-α-pent-3-enopyranosyl)nucleoside derivatives of thymine (10a), uracil (10b), 5-fluorouracil (10c) and N⁴-benzoyl cytosine (10d). Only the first approach could afford derivative 10d. Debenzoylation of 10d afforded 1-(2,3,4-trideoxy-2-methylene-α-pent-3-enopyranosyl)cytosine (10f). The first approach resulted also to the 2-keto-3,4-unsaturated analogs 9. The new analogs did not show inhibition of DNA and RNA virus replication in cell culture. The 2′-ketonucleoside derivatives 9 were found to be more cytostatic than the corresponding 2′-exomethylene nucleosides 10. The 5-fluorouracil unsaturated keto derivative 9c and the exomethylene derivatives 10c and 13c showed antiproliferative activity in the lower micromolar range. Experimental evidence revealed that 9c, 10c and 13c may act as novel types of 5-fluorouracil releasing prodrugs, and points to thymidylate synthase as target for their cytostatic action.     

Bacterial Bloodstream Infections in HIV-infected Adults Attending a Lagos Teaching Hospital

An investigation was carried out during October 2005–September 2006 to determine the prevalence of bloodstream infections in patients attending the outpatient department of the HIV/AIDS clinic at the Lagos University Teaching Hospital in Nigeria. Two hundred and one patients—86 males and 115 females—aged 14-65 years were recruited for the study. Serological diagnosis was carried out on them to confirm their HIV status. Their CD4 counts were done using the micromagnetic bead method. Twenty mL of venous blood sample collected from each patient was inoculated into a pair of Oxoid Signal blood culture bottles for 2-14 days. Thereafter, 0.1 mL of the sample was plated in duplicates on MacConkey, blood and chocolate agar media and incubated at 37 °C for 18-24 hours. The CD4+ counts were generally low as 67% of 140 patients sampled had <200 cells/μL of blood. Twenty-six bacterial isolates were obtained from the blood samples and comprised 15 (58%) coagulase-negative staphylococci as follows: Staphylococcus epidermidis (7), S. cohnii cohnii (1), S. cohnii urealyticum (2), S. chromogenes (1), S. warneri (2), S. scuri (1), and S. xylosus (1). Others were 6 (23%) Gram-negative non-typhoid Salmonella spp., S. Typhimurium (4), S. Enteritidis (2); Pseudomonas fluorescens (1), Escherichia coli (1), Ochrobactrum anthropi (1), Moraxella sp. (1), and Chryseobacterium meningosepticum. Results of antimicrobial susceptibility tests showed that coagulase-negative staphylococci had good sensitivities to vancomycin and most other antibiotics screened but were resistant mainly to ampicilin and tetracycline. The Gram-negative organisms isolated also showed resistance to ampicillin, tetracycline, chloramphenicol, and septrin. This study demonstrates that co-agulase-negative staphylococci and non-typhoidal Salmonellae are the most common aetiological agents of bacteraemia among HIV-infected adults attending the Lagos University Teaching Hospital, Nigeria. The organisms were resistant to older-generation antibiotics often prescribed in this environment but were sensitive to vancomycin, cefotaxime, cefuroxime, and other new-generation antibiotics.Key words: Bacteraemia, Bacterial infections, HIV, HIV infections, Nigeria     

Comparison of the effects of three different <Emphasis Type="Italic">Baccaurea angulata</Emphasis> whole fruit juice doses on plasma,aorta and liver MDA levels,antioxidant enzymes and total antioxidant capacity

Purpose

Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0.50, 1.00 and 1.50 ml/kg/day on plasma, aorta and liver malondialdehyde (MDA) levels, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as total antioxidant capacity in rabbits fed high-cholesterol diet.

Methods

Thirty-five male rabbits of New Zealand strain were randomly assigned to seven groups. For 12 weeks, group CH was fed 1% cholesterol diet only; group C1 was fed 1% cholesterol diet and 0.50 ml/kg/day B. angulata WF juice; group C2 was fed 1% cholesterol diet and 1.00 ml/kg/day B. angulata WF juice; group C3 was fed 1% cholesterol diet and 1.50 ml/kg/day B. angulata WF juice; group N was fed standard pellet only; group N1 was fed standard pellet and 0.50 ml/kg/day B. angulata WF juice; and group N2 was fed standard pellet and 1.00 ml/kg/day B. angulata WF juice.

Results

The three doses reduced the formation of MDA and enhanced the expression of endogenous antioxidant enzymes. The highest dose used (1.50 ml/kg/day) was, however, seen as the most potent.

Conclusion

Higher doses of B. angulata juice exerted better antioxidant activity.

     

Design, synthesis and molecular docking studies of novel triazole as antifungal agent

In order to meet the urgent need for novel antifungal agents with improved activity and broader spectrum, a series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted trifluoromethyl phenyl)-piperazin-1-yl]-propan-2-ols were designed, synthesized and evaluated as antifungal agents. The MIC₈₀ values indicate that the compounds 7a-7q, 8a-8d showed higher antifungal activities against Candida albicans than 5a-5i, 6a-6j. Moreover, the molecular model for the binding between compound 5a, 7a and the active site of CACYP51 was provided based on the computational docking results, and the structure-activity relationship was analyzed.     

Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines

Synthesis of a new series of diarylureas and diarylamides having 1H-pyrrolo[3,2-c]pyridine scaffold is described. Their in vitro antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on pyrrolo[3,2-c]pyridine nucleus was investigated. The newly synthesized compounds, except three N-tolyl derivatives (8f, 9f, and 9h), generally showed superior activity against A375P to Sorafenib. Among all of these derivatives, compounds 8b, 8g, and 9a-e showed the highest potency against A375P with IC₅₀ in nanomolar range. In addition, compounds 8d, 8e, 8h, 9g, 9i, and 9j were more potent than Sorafenib but with IC₅₀ in micromolar range. Compounds 8b, 8g, 9b-d, and 9i demonstrated higher selectivity towards A375P compared with NIH3T3 fibroblasts. The most potent diarylurea 8g and diarylamide 9d were further tested and showed high potency over nine melanoma cell lines at the NCI.     

Evaluating and establishing national norms for mental wellbeing using the short Warwick–Edinburgh Mental Well-being Scale (SWEMWBS): findings from the Health Survey for England

Purpose

The Warwick–Edinburgh Mental Well-being Scale (WEMWBS), 14 positively worded statements, is a validated instrument to measure mental wellbeing on a population level. Less is known about the population distribution of the shorter seven-item version (SWEMWBS) or its performance as an instrument to measure wellbeing.

Methods

Using the Health Survey for England 2010–2013 (n = 27,169 adults aged 16+, nationally representative of the population), age- and sex-specific norms were estimated using means and percentiles. Criterion validity was examined using: (1) Spearman correlations (ρ) for SWEMWBS with General Health Questionnaire (GHQ-12), happiness index, EQ-VAS (2) a multinomial logit model with SWEMWBS (low, medium and high wellbeing) as the outcome and demographic, social and health behaviours as explanatory variables. Relative validity was examined by comparing SWEMWBS with WEMWBS using: (1) Spearman correlations (continuous data), and (2) the weighted kappa statistic (categorical), within population subgroups.

Results

Mean (median) SWEMWBS was 23.7 (23.2) for men and 23.2 (23.2) for women (p = 0.100). Spearman correlations were moderately sized for the happiness index (ρ = 0.53, P < 0.001), GHQ-12 (ρ = ?0.52, p < 0.001) and EQ-VAS (ρ = 0.40, p < 0.001). Participants consuming <1 portion of fruit and vegetables a day versus ≥5 (odds ratio = 1.43 95% Confidence Interval = (1.22–1.66)) and current smokers versus non-smokers (1.28 (1.15–1.41)) were more likely to have low vs medium wellbeing. Participants who binge drank versus non-drinkers were less likely to have high versus medium wellbeing (0.81 (0.71–0.92)). Spearman correlations between SWEMWBS and WEMWBS were above 0.95; weighted kappa statistics showed almost perfect agreement (0.79–0.85).

Conclusion

SWEMWBS distinguishes mental wellbeing between subgroups, similarly to WEMWBS, but is less sensitive to gender differences.

     

Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (8f) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo.     

The validity of the Satisfaction with Life Scale in adolescents and a comparison with single-item life satisfaction measures: a preliminary study

Purpose

The validity of the life satisfaction measures commonly used among adults has been rarely examined in adolescent samples. The present research had two main goals: (1) to evaluate the structural validity of the Satisfaction with Life Scale (SWLS) among adolescents and to test measurement invariance across gender; (2) to compare the criterion and convergent validity of the SWLS and single-item life satisfaction measures among adolescents.

Methods

Three samples of Serbian adolescents were recruited for the present research. Study 1 (N = 481, M _age = 17.01 years) examined the structure of the SWLS via confirmatory factor analysis (CFA) and evaluated measurement invariance of the SWLS across gender by a multi-group CFA. Study 2 (N = 283, M _age = 17.34 years) and Study 3 (N = 220, M _age = 16.73 years) compared the convergent validity of the SWLS and single-item life satisfaction measures.

Results

The results of Study 1 supported the original one-factor model of the SWLS among adolescents and provided evidence for strong measurement invariance of the SWLS across gender. The findings of Study 2 and Study 3 showed that the SWLS and single-item measures were equally valid and strongly associated (r = .734 in Study 2 and r = .668 in Study 3). No substantial differences in correlations with school success and well-being indicators were found between the SWLS and single-item measures.

Conclusions

Our findings support the use of the SWLS among adolescents and indicate that single-item life satisfaction measures perform as well as the SWLS in adolescent samples.

     

Affective disorders and Health-Related Quality of Life (HRQoL) in adolescents and young adults with Multiple Sclerosis (MS): the moderating role of resilience

Purpose

To investigate the moderating role of resilience in the relationship between affective disorders and Health-Related Quality of Life (HRQoL) for adolescents and young adults with multiple sclerosis (MS).

Methods

A quantitative methodology was adopted. Fifty-three adolescents and young adults were interviewed to assess resilience as a personality trait (Ego-Resiliency Scale) and resilience as an interactive competence (CYRM-28), Health-Related Quality of Life (PedsQL 4.0), depression and anxiety (BDI-II and STAI-Y).

Results

Affective disorders, both depression (β = ?.38, p < .001) and anxiety (State β = –.35, p < .001; Trait β = ?.41, p < .001), were negatively associated with HRQoL. Data also showed that the resilience competencies using Individual (β = .22, p < .001) and relational resources (β = .12, p < .05) are significantly associated HRQoL. According to the regression analyses, we tested the moderating role of resilience competence using individual resources on the relationship between the Depression Cognitive Factor and Emotional Functioning. Data show that in step 2 of the regression analysis, we obtained a variation of β = ?.45 (p < .001) to β = ?.30 (p < .001) in the dimension for the Depression Cognitive Factor. The Sobel test showed that the moderating effect of resilience was significant regarding the increase in R² (p < .01).

Conclusions

Resilience competence using individual resources moderates the relationship between the Depression Cognitive Factor and Emotional Functioning in adolescents with MS. Our study suggests that to improve well-being for adolescents with MS resilience could play a key role.

     

Part I: Synthesis, cancer chemopreventive activity and molecular docking study of novel quinoxaline derivatives

The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1-21 has been evaluated by studying their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds 1-21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent cancer chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.     

Correlates of health-related quality of life in young-old and old–old community-dwelling older adults

Purpose

This study aimed (1) to examine the role of potential correlates of HRQoL in a large representative sample of older adults, and (2) to investigate whether the relationships between HRQoL and potential factors differ as a function of HRQoL component (physical vs. mental) and/or age cohort (young-old vs. old–old).

Methods

This cross-sectional study included 802 older adults aged 60–79 years old. HRQoL was assessed using the SF-36 questionnaire. Functional fitness was assessed using the Senior Fitness Test. Physical activity was measured via the Baecke questionnaire. Demographic information, mental and health features were obtained through questionnaires.

Results

A multiple regression analysis showed that BMI (β = ?0.15, p?=?0.001), body strength (β =?0.21, p?<?0.001), aerobic endurance (β =?0.29, p?<?0.001), physical activity (β =?0.11, p?=?0.007), depressive symptoms (β = ?0.19, p?<?0.001), falls (β = ?0.19, p?<?0.001), and living alone (β = ?0.16, p?<?0.001) were all significantly related to HRQoL-SF-36 total score. The positive relation with aerobic endurance was significantly higher for the physical component of HRQoL, while the negative relation with living alone was significantly higher for the mental component. The positive relation of HRQoL with physical activity was significantly higher in old–old compared to young-old adults.

Conclusion

This data suggest that body composition, functional fitness, psycho-social factors, and falls are important correlates of HRQoL in old age. There are HRQoL-component and age-cohort differences regarding these correlates, underlying the need for specific strategies at the community level to promote HRQoL in older adults.

     

Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication

9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 °C in several media.