The present study evaluated the neuroprotective effects of one selenium-containing AZT derivative compound (S1073) in memory and learning impairment caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice causes impairment of energy metabolism with oxidative damage and cholinergic dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection received a bilateral dose of STZ [11.3 μmol/l]. After 8 days' STZ injection, we performed the behavioral experiments (Beaker test, Open field and Morris water maze task). ICV-STZ caused significant learning and memory impairments, which were significantly improved by S1073 pre-treatment. A significant increase in cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and learning were observed in ICV-STZ injected animals. S1073 significantly ameliorated all alterations induced by ICV-STZ in mice. All these findings support the neuroprotective role of S1073 in mice model of Alzheimer's dementia-type induced by ICV-STZ, which may be associated with its antioxidant activity and/or with its inhibitory effect in brain AChE. In fact, in silico analysis indicated that S1073 may be an inhibitor of AChE.

In the previous studies of our lab, the thiophene[3,2-d]pyrimidine was identified as a promising scaffold for seeking highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). In the present study, we designed, synthesized, and biologically evaluated a series of thiophene[3,2-d]pyrimidine derivatives with changed linker between the thiophenepyrimidine core and the right wing. Some of the synthesized compounds exhibited excellent HIV-1 inhibitory potency with low (double-digit) nanomolar EC50 values. Among them, compound 13a exhibited the most potent anti HIV-1 activity (EC50 = 21.2 nM), which was 10-fold greater than that of NVP (EC50 = 281 nM). Moreover, 13a showed much lower cytotoxicity (CC50 = 183 μM) and higher SI (SI = 8632) than NVP, ETV and AZT. Besides, some physicochemical properties and water solubility were calculated or measured. The preliminary structure-activity relationships and molecular simulation studies of these compounds were also discussed comprehensively to provide valuable direction for further design and optimization. This article is protected by copyright. All rights reserved.

The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons.

Despite the efficacy of combination chemotherapy with arsenic trioxide (ATO), interferon α (IFN) and zidovudine (AZT) for adult T cell leukemia/lymphoma (ATL), the precise mechanism underlying this combination treatment effect is unknown. In the present study, ATO/IFN/AZT was examined in an ATL leukemic cell line (S1T, non-Tax expressing), a human T-lymphotropic virus 1 (HTLV-1)-infected cell line (MT2, Tax-expressing) and primary ATL cells from patients with acute and chronic ATL. IFN/AZT marginally inhibited MT2 cell proliferation, but substantially inhibited S1T cell proliferation. IFN/AZT increased the cleavage of numerous caspases and PARP in S1T cells, and regulated the signal transducer and activator of transcription 1 and nuclear factor-κB signaling pathway. These effects represent the potential anti-ATL mechanisms of INF/AZT in vitro. In addition, the combination of ATO and IFN/AZT demonstrated synergistic effects on S1T cells. Therefore, the Tax-independent mechanism underlying the anti-ATL effect of ATO must be further elucidated.

Objective: To understand the prevalence of drug resistance in treatment-naive HIV infected men who have sex with (MSM) in Guangzhou. Methods: HIV-1 RNA were extracted from the serum specimens of the MSM newly confirmed to be HIV-1 positive, living in Guangzhou and receiving no anti-viral therapy from 2008 to 2015. HIV-1 pol gene segments, including full protease and part reverse transcriptase, were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and sequenced by Sanger. Subsequently, the sequence data were submitted to Stanford University HIV Drug Resistance Database for drug resistance analysis. Results: Among 2 283 HIV infected MSM, HIV-1 pol gene segments were obtained from the serum samples of 1 986 HIV infected MSM aged 16-84 (30.18±8.24) years. Among them, the unmarried accounted for 74.17% (1 473/1 986), those of Han ethnic group accounted for 90.64% (1 800/1 986), those with education level of college or above accounted for 49.65% (986/1 986), those with education level of senior high school or secondary school accounted for 27.14% (539/1 986), those with education level of junior high school or below accounted for 20.89% (415/1 986). The distribution of subtypes was predominated by CRF07_BC (38.22%, 759/1 986) and CRF01_AE (34.49%, 685/1 986). The overall prevalence of drug resistance was 3.32% (66/1 986). The prevalence of resistance to protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 1.36%(27/1 986), 0.65% (13/1 986) and 1.61% (32/1 986), respectively. Subtype B had higher resistance to PIs, NRTIs and NNRTIs and subtype CRF55_01B had highest resistance to NNRTIs compared with other subtypes. In subtype B, the resistant rates to D4T, EFV and NVP were highest (all 4.17%, 5/120), followed by those to NFV, AZT and RPV (all 3.33%, 4/120). In subtype CRF55_01B, the resistant rates to EFV and NVP were highest (all 5.50%, 16/291), followed by those to ETR and RPV (all 5.15%, 15/291). Conclusions: The prevalence of drug resistance in treatment-naive HIV infected MSM in Guangzhou remained at low level and current antiretroviral drugs are generally effective. However, subtype B and CRF55_01B have higher drug resistance.

Zidovudine (AZT) adsorbed on colloidal gold nanoparticles (AuNPs) undergoes pH-induced conformational changes according to spectral changes in surface-enhanced Raman scattering (SERS). In acidic pH values conditions, AZT assumes the C(2')-endo conformer, which binds more weakly to AuNPs than under neutral and alkaline conditions. In this study, density functional theory (DFT) calculations were performed; these calculations also supported the conformation-dependent binding energies. A lactobionic acid-conjugated PEGylated (LA-PEG-SH; molecular weight: 3400) unit was attached to AuNPs to target the asialoglycoprotein receptors overexpressed in hepatocarcinoma cells of Huh7 and SNU-354. The loading efficiency values were measured to be ∼44-49% and ∼66-68% at pH values of 7 and 10, respectively. At an acidic pH of 4.5, they were estimated to be only ∼35-38%. pH-dependent spectral changes were observed for the asymmetric stretching modes of the azide (NNN) bands at 2183 cm-1 (in acidic pH) and at 2129 cm-1 (in basic pH). Cell viability analysis indicated that the LA-PEG-capped, AZT-coated AuNPs specifically inhibited the growth of the targeted hepatocarcinoma cells with better cancer cell killing efficiency than was observed with the LA-PEG-capped AuNPs without AZT.

Reverse transcriptase inhibitors (RTIs), including nucleoside RTIs (NRTIs) and non-nucleoside RTIs (NNRTIs), are critical antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infection. Emergence of multi-RTI resistance calls for the development of more potent therapeutics or regimens against RTI-resistant strains. Here, we demonstrated that combining azidothymidine (AZT) with a new NNRTIs under development, diarylpyridine (DAPA)-2e, diarylanilin (DAAN)-14h, or DAAN-15h, resulted in strong synergism against infection by divergent HIV-1 strains, including those resistant to NRTIs and NNRTIs, suggesting the potential for developing these novel NNRTIs as salvage therapy for HIV/acquired immune deficiency syndrome (AIDS) patients.

In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. Zidovudine has been well studied during breastfeeding. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through at least 12 months of life up to 24 months of life.[1] The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.[2][3] Breastfed infants whose mothers receive a highly active antiretroviral (HAART) regimen containing zidovudine have higher rates of neutropenia during the first month and severe anemia during the first 6 months of life.