Docking-based 3D-QSAR study of HIV-1 integrase inhibitors

Gupta, Pawan; Roy, Nilanjan; Garg, Prabha

doi:10.1016/j.ejmech.2009.07.010

Cited by 38 publications

(31 citation statements)

References 50 publications

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“…In the hydrophobic maps of CoMSIA (right, Figure 8), yellow contour indicated regions where hydrophobic substituents were favorable to enhance activity. A large yellow polyhedron indicated substitution of hydrophobic group on 1‐ and 3‐position of the benzene ring might have an enhancing effect on activities (25). According to the results from CoMSIA model, the structure of compound ( 25‐F5 ) with the higher neuraminidase inhibitory activity was optimized, and the designed compound (compound A ) (Figure 9) was predicted to have higher activity (with pIC 50 value of 7.627).…”

Section: Resultsmentioning

confidence: 99%

Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors

et al. 2011

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Neuraminidase (NA) is a major glycoprotein of influenza virus which is essential for viral infection. It offers a potential target for antiviral drug design and discovery. To develop novel potent neuraminidase inhibitors (NAI), Surflex-Dock was employed to dock 40 hydrophobic p-aminosalicylic acid derivatives into the active site of NA. The 3D-quantitative structure-activity relationship studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were carried out on 40 molecules. Both CoMFA (q(2) = 0.628, r(2) = 0.697) and CoMSIA (q(2) = 0.746, r(2) = 0.816) gave reasonable results. A preliminary pharmacokinetic profile of these NAI was also performed on the basis of Volsurf predictions. The results obtained from this study will be useful in the design of novel potent NAI.

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Section: Resultsmentioning

confidence: 99%

Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors

et al. 2011

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“…The residues within a radius of 6.5 Å around the SAV (the ligand of VEGFR-2 in the crystal structure 3CJF) in VEGFR-2 were selected as the active sites. Other docking parameters of the program were maintained at a default setting [31]. The virtual docking of VEGFR-2 in complex with the inhibitors has provided a basis for further studies aimed at identifying inhibitors of VEGF-induced angiogenesis, and has provided valuable information regarding the structurebased design of novel biphenyl VEGFR-2 TK inhibitors.…”

Section: Molecular Modelingmentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of Novel Symmetrical Taspine Derivatives as Anticancer Agents

Zhang¹,

Zhang²,

Pan³

et al. 2011

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It has been demonstrated that taspine derivatives act as anticancer agents, thus we designed and synthesized a novel class of symmetrical biphenyl derivatives. We evaluated the cytotoxicity and antitumor activity of biphenyls against five human tumor and normal cell lines. The results indicated that the majority of the compounds exhibited anticancer activity equivalent to or greater than the positive control. Compounds (11) and (12) demonstrated the most potent cytotoxic activity with IC₅₀ values between 19.41 µM and 29.27 µM. The potent antiproliferative capabilities of these compounds against ECV304 human transformed endothelial cells indicated that these biphenyls could potentially serve as antiangiogenic agents. We also reviewed the relationship between structure and activity based on the experimental results. Our findings provide a good starting point for further development of symmetrical biphenyl derivatives as potential novel anticancer agents.

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“…Integrase (IN), a 32 kDa protein in Human Immunodeficiency Virus (HIV), is a promising anti-HIV target and several classes of inhibitors have been reported (Gupta, Roy & Garg 2009; Plewe et al 2009; Cheng, Zhang & Fu 2010; Tanis et al 2010; Johnson et al 2011; Sharma et al 2011; Telvekar & Patel 2011). IN active-site-directed strand transfer inhibitors, Raltegravir, Elvitegravir and Dolutegravir have been approved by Food and Drug Administration for anti-retroviral therapy (http://aidsinfo.nih.gov/guidelines; Summa et al 2008; Volberding & Deeks 2010).…”

Section: Introductionmentioning

confidence: 99%

The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study

Balasubramanian

Rangarajan

Bojja

et al. 2016

Journal of Biomolecular Structure and Dynamics

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Retroviral integrases are reported to form alternate dimer assemblies like the core-core dimer and reaching dimer. The core-core dimer is stabilized predominantly by an extensive interface between two catalytic core domains. The reaching dimer is stabilized by N-terminal domains (NTD) that reach to form intermolecular interfaces with the other subunit’s core and C-terminal domains (CTD), as well as CTD-CTD interactions. In this study, molecular dynamics (MD), Brownian dynamics (BD) simulations, and free energy analyses, were performed to elucidate determinants for the stability of the reaching dimer forms of full-length ASV and HIV IN, and to examine the role of the C-tails (the last ~16–18 residues at the C-termini) in their structural dynamics. The dynamics of an HIV reaching dimer derived from SAXS and protein crosslinking data, was compared with the dynamics of a core-core dimer model derived from combining the crystal structures of two-domain fragments. The results showed that the core domains in the ASV reaching dimer express free dynamics, whereas those in the HIV reaching dimer are highly stable. Brownian dynamics simulations suggest a higher rate of association for the HIV core-core dimer than the reaching dimer. The predicted stability of these dimers was therefore ranked in the following order: ASV reaching dimer

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Docking-based 3D-QSAR study of HIV-1 integrase inhibitors

Cited by 38 publications

References 50 publications

Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors

Molecular Docking, 3D‐QSAR Studies, and In Silico ADME Prediction of p‐Aminosalicylic Acid Derivatives as Neuraminidase Inhibitors

Synthesis and Cytotoxic Evaluation of Novel Symmetrical Taspine Derivatives as Anticancer Agents

The conformational feasibility for the formation of reaching dimer in ASV and HIV integrase: a molecular dynamics study

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