Design, synthesis and biological activity of DB02 amino acid derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors / 药学学报

To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.

A study of profile of patients failing first line NACO recommended ART

Background: Failure of first line NACO recommended Therapy has been reported in 1-5% cases of HIV/AIDS. Various factors are associated with failure. This study describes the profile of patients failing first line ART (FLA) in a predominately lower socioeconomic population. The objective of the present study was to identify factors associated with failure of FLA.Methods: Retrospective data analysis of patients failing first line therapy. Epidemiological information, clinical parameters and laboratory reports were taken into consideration. Data was analysed as per standard statistical analysis.Results: Out of a total 3926 patients on first line ART for varying periods of time from our ART centre 54 patients were on second line ART. Males (2.20%) had a high failure rate than females (0.50%). The average time of failure was 64.11 months with a median of 56.50 months. 74.1% (40/54) of the patients had very low CD4 count at the time of initial diagnosis. Failure rate of FLA was higher in the patients having Stavudine based regimen (NRTI) (6.61%) and 3.64% in patients having Nevirapine based regimen (NNRTI).Conclusions: Second line therapy is required only in a small number of patients at present, but as it is related to the duration on first line ART and also with initial low CD4 count, more and more patients will require SLA in the near future.

The anti-HIV-1 activities of benzophenones non-nucleoside reverse transcriptase inhibitors in vitro / 药学学报

To evaluate the anti-HIV-1 activities of 5 benzophenones non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as DY1203, DY1204, DY1119, DY1208 and DY1209 in vitro, the cytotoxicity of 5 compounds were tested on C8166, MT-4, H9 and PBMC with the MTT assay. The anti-HIV-1 activities of compounds were evaluated on laboratory-adapted strain, drug-resistant strains and primary isolated strains by p24 antigen expression ELISA. The inhibition of HIV-1 recombinant reverse transcriptase activity was assessed by ELISA assay. Among 5 compounds, DY1203 and DY1204 showed low cytotoxicities with CC50 greater than 200 μg·mL-1. DY1119, DY1208 and DY1209 showed strong anti-HIV-1 activities against HIV-1IIIB, HIV-174V, HIV-1RF/V82F/184V, HIV-1NL4-3 gp41(36G) N42S, HIV-1KM018, HIV-1TC-1 and HIV-1Wan. However, NNRTIs drug-resistant strain HIV-1A17 showed different resistance to these compounds. The 5 compounds proved active against HIV-1 recombinant reverse transcriptase. DY1208 is expected to become a new lead compound for its high therapeutic index. The results can provide new information for HIV-1 drug research and promote the development of new HIV-1 drugs.

Formulation and in vitro evaluation of nevirapine extended release matrix tablets.

Objective: Nevirapine (NVP) is a non nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. The present study was aimed to develop generic formulation of extended release (ER) tablets of Nevirapine anhydrous (NVP) using hydrophilic polymer. Method: Nevirapine NVP(ER) tablets were prepared by different manufacturing technology i.e. direct compression, roller compaction, and wet granulation method by employing hydrophilic polymer (HPMC K15M).The matrix granules were prepared by mixing drug along with polymer and diluents in different polymer ratio from wet granulation technology used water as a granulating fluid. Results: The prepared granules were evaluated for various physicochemical parameters by official procedure and compressed in tablets. The In-vitro release profile of various batches was prepared by different technologies and has been compared with the innovator product. In-vitro release profiles of NVP from ER tablets were determined using USP apparatus type II (Paddle), 50 rpm and bath temperature 37ºC. Dissolution of tablets was carried out in 900 ml of media (phosphate buffer pH 6.8). Samples were withdrawn at predetermined time intervals up to 24 hrs and analyzed using UV detector at a wavelength of 247 nm. Conclusion: Stress stability studies indicated that the formulation is stable and In-vitro release profile study showed that formulation using wet granulation technology.

Nevirapine, a non-nucleoside reverse transcriptase inhibitor / 中国临床药理学与治疗学

Acquired immune deficiency syndrome (AIDS), a great epidemic t hreatening disease, is caused by the human immunodeficiency virus (HIV), particu larly the strain known as HIV-1. Nevirapine, a novel non-nucleoside reverse tr anscriptase (RT) inhibitor combined with nucleoside analogue RT inhibitors or pr otease inhibitors, can be used in treatment of patients with HIV infection. AS a n agent used alone, nevirapine can prevent vertical transmission or HIV infectio n.