ArticleChemMedChem2010
Tautomerism and magnesium chelation of HIV-1 integrase inhibitors: a theoretical study.
Article in ChemMedChem, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed, 13 citations in OpenAlex.
- Quantum mechanics implementation in drug-design workflows: does it really help?Drug design, development and therapy · 2017Review
- Software and resources for computational medicinal chemistry.Future medicinal chemistry · 2011Review
- Computer tools in the discovery of HIV-1 integrase inhibitors.Future medicinal chemistry · 2010Review
- Authentic HIV-1 integrase inhibitors.Future medicinal chemistry · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The tautomerism and corresponding transition states of four authentic HIV-1 integrase (IN) inhibitor prototype structures, alpha,gamma-diketo acid, alpha,gamma-diketotriazole, dihydroxypyrimidine carboxamide and 4-quinolone-3-carboxylic acid, were investigated at the B3LYP/6-311++G(d,p) level in vacuum and in aqueous solvent models. To study the possible chelating modes of these tautomers with two magnesium ions--a process important for inhibition--we modeled an assembly of three formic acids, four water molecules and two Mg(2+) ions as a template mimicking the binding site of IN. The DFT calculation results show that deprotonated enolized or phenolic hydroxy groups of specific tautomers in water lead to the most stable complexes, with the two magnesium ions separated by a distance of approximately 3.70 to 3.74 A, and with each magnesium ion at the center of an octahedron. The drug candidate GS-9137 (Gilead), based on the 4-quinolone-3-carboxylic acid scaffold, and its analogues form similar but different chelating modes. When one water molecule in the complex is replaced by a methanol molecule, which mimics the terminal 3'-OH of viral DNA, a good chelating complex is retained. This supports the hypothesis that, in the binding site of IN after 3'-processing, the terminal 3'-OH of viral DNA interacts with one Mg(2+) by chelation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.