Recent Advances in Small-Molecule HIV-1 Integrase Inhibitors

Zhang, Chao; Xie, Qian; Wan, C. C.; Jin, Zhe; Hu, Chun

doi:10.2174/0929867328666210114124744

Cited by 6 publications

(8 citation statements)

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“…Since most of the reported INSTIs contain halogenated phenyl groups near the chelating core, 46 the effect of C5 position on the indole structure was then evaluated. According to the preliminary design, a halogenated benzene ( 13a ) or pyrazine ( 13b ) was introduced at the 5-position of compound 1 via an amide bond.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors

Zhang,

Chen,

Wang

et al. 2024

RSC Adv.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors

Zhang,

Chen,

Wang

et al. 2024

RSC Adv.

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“…Chemically novel and potential lead compounds could be possibly identified from the database containing 1916 compounds (71 HIV-1 integrase inhibitors [ 27 ], 37 antibacterial inhibitors, 131 antiviral inhibitors and 1677 other approved drugs by FDA) by virtual screening based on the generated pharmacophore [ 10 ]. Pharmacophore-based virtual screening was used to initiate the identification of novel scaffolds as PA N endonuclease inhibitors and the validated pharmacophore Hypo1 was utilized as a 3D query for screening the database [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Well validated pharmacophore Hypo1 was used as a 3D query for identifying potential leading molecules from a chemical database which containing 71 HIV-1 integrase inhibitors [27] as previously reported and additional 1845 drugs (37 antibacterial inhibitors, 131 antiviral inhibitors and 1677 other approved drugs by FDA) that obtained from ZINC database (ZINC, http://zinc.docking.org (accessed on 7 November 2021).). The fast search method was carried out to obtain the 'hit' compounds matching with the features in the best pharmacophore Hypo1.…”

Section: Database Screeningmentioning

confidence: 99%

“…We also constructed 10 pharmacophore models with activity prediction ability by utilizing the three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) Pharmacophore (HypoGen algorithm) technique. Then we screened a chemical database containing 1916 compounds (71 human immunodeficiency virus type 1 (HIV-1) integrase inhibitors [ 27 ], 37 antibacterial inhibitor, 131 antiviral inhibitors and 1677 approved drugs by FDA) based on the best pharmacophore Hypo1. Among the 1916 small-molecule inhibitors, part of them could form a chelate with two divalent metal ions, such as the HIV-1 integrase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Influenza PAN Endonuclease Inhibitors via 3D-QSAR Modeling and Docking-Based Virtual Screening

et al. 2021

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Structural and biochemical studies elucidate that PAN may contribute to the host protein shutdown observed during influenza A infection. Thus, inhibition of the endonuclease activity of viral RdRP is an attractive approach for novel antiviral therapy. In order to envisage structurally diverse novel compounds with better efficacy as PAN endonuclease inhibitors, a ligand-based-pharmacophore model was developed using 3D-QSAR pharmacophore generation (HypoGen algorithm) methodology in Discovery Studio. As the training set, 25 compounds were taken to generate a significant pharmacophore model. The selected pharmacophore Hypo1 was further validated by 12 compounds in the test set and was used as a query model for further screening of 1916 compounds containing 71 HIV-1 integrase inhibitors, 37 antibacterial inhibitors, 131 antiviral inhibitors and other 1677 approved drugs by the FDA. Then, six compounds (Hit01–Hit06) with estimated activity values less than 10 μM were subjected to ADMET study and toxicity assessment. Only one potential inhibitory ‘hit’ molecule (Hit01, raltegravir’s derivative) was further scrutinized by molecular docking analysis on the active site of PAN endonuclease (PDB ID: 6E6W). Hit01 was utilized for designing novel potential PAN endonuclease inhibitors through lead optimization, and then compounds were screened by pharmacophore Hypo1 and docking studies. Six raltegravir’s derivatives with significant estimated activity values and docking scores were obtained. Further, these results certainly do not confirm or indicate the seven compounds (Hit01, Hit07, Hit08, Hit09, Hit10, Hit11 and Hit12) have antiviral activity, and extensive wet-laboratory experimentation is needed to transmute these compounds into clinical drugs.

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“…The regimen comprises TDF, 3TC, emtricitabine, and an integrase inhibitor, which can block HIV integrase, an enzyme that HIV needs to make copies of itself. [18]…”

Section: Discussionmentioning

confidence: 99%

Recommend Guideline on Prevention of Mother-to-Child Transmission of HIV in China in 2020

Qu,

Wang,

Wang

et al. 2023

Infect Dis Immun

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In China, a pilot project for the prevention of mother-to-child transmission (PMTCT) of the HIV was initiated in 2001. For the PMTCT of HIV, the Chinese government has released versions of the guidelines since 2004. In 2014, the World Health Organization released guidance on global processes and criteria for the validation of elimination of mother-to-child transmission of HIV and syphilis. To promote the elimination of mother-to-child transmission of HIV, syphilis, and hepatitis B virus in China, the Chinese government updated the Guideline for PMTCT of HIV, Syphilis, and Hepatitis B in 2020 (briefly as Guideline-2020). The Guideline-2020 comprises 5 parts: goals, interventions, support measures, duties and cooperation of departments, and definition indicators for PMTCT of HIV and corresponding calculation formulas. Compared with the previous versions, the key points updated in the Guideline-2020 are that the goals are set again, and health education and promotion, the procedure of HIV testing for pregnant women, and the antiretroviral therapy regimen for HIV-positive pregnant women and antiretroviral) prophylaxis regimen for infants are all updated. The antiretroviral prophylaxis regimen as zidovudine-lamivudine-nevirapine/lopinavir/ritonavir twice per day for 6 weeks is recommended for infants at high exposure risk to HIV, whereas the third antiretroviral therapy regimen as tenofovir-lamivudine-lopinavir/ritonavir is recommended for HIV-positive pregnant women, and indicators for PMTCT of HIV and corresponding calculation formulas are defined.

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Recent Advances in Small-Molecule HIV-1 Integrase Inhibitors

Cited by 6 publications

References 0 publications

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors

Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors

Identification of Influenza PAN Endonuclease Inhibitors via 3D-QSAR Modeling and Docking-Based Virtual Screening

Recommend Guideline on Prevention of Mother-to-Child Transmission of HIV in China in 2020

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