Synthesis and Antiviral Activity Evaluation of Some Aminoadamantane Derivatives

Kolocouris, Nicolas; Foscolos, George B.; Kolocouris, Antonios; Marakos, Panayotis; Pouli, Nicole; Fytas, George; Ikeda, Satoru; Clercq, Erik De

doi:10.1021/jm00044a010

Cited by 120 publications

(86 citation statements)

References 20 publications

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“…The desolvation penalty (∆G polar solv. ) favored compounds I, II, and III over 8, whereas the desolvation pentalty of IV is more disfavorable than that of 8 (Figure 5), likely due to a larger decrease in polar solvation of the terminal NH 3 group upon binding of IV to M2TM.While the synthesis of I was described,114 the compound has not yet been evaluated with respect to the binding affinity towards M2TM Weybridge . ITC measurements against M2TM Weybridge , performed after the above prioritization by the MM-PBSA computations,…”

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confidence: 99%

Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations

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Ioannidis

Kolarov

et al. 2016

J. Chem. Inf. Model.

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The development of novel anti-influenza drugs is of great importance because of the capability of influenza viruses to occasionally cross interspecies barriers and to rapidly mutate. One class of anti-influenza agents, aminoadamantanes, including the drugs amantadine and rimantadine now widely abandoned due to virus resistance, bind to and block the pore of the transmembrane domain of the M2 proton channel (M2TM) of influenza A. Here, we present one of the still rare studies that interprets thermodynamic profiles from isothermal titration calorimetry (ITC) experiments in terms of individual energy contributions to binding, calculated by the computationally inexpensive implicit solvent/implicit membrane molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approach, for aminoadamantane compounds binding to M2TM of the avian "Weybridge" strain. For all eight pairs of aminoadamantane compounds considered, the trend of the predicted relative binding free energies and their individual components, effective binding energies and changes in the configurational entropy, agrees with experimental measures (ΔΔG, ΔΔH, TΔΔS) in 88, 88, and 50% of the cases. In addition, information yielded by the MM-PBSA approach about determinants of binding goes beyond that available in component quantities (ΔH, ΔS) from ITC measurements. We demonstrate how one can make use of such information to link thermodynamic profiles from ITC with structural causes on the ligand side and, ultimately, to guide decision making in lead optimization in a prospective manner, which results in an aminoadamantane derivative with improved binding affinity against M2TM(Weybridge).

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confidence: 99%

Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations

Homeyer

Ioannidis

Kolarov

et al. 2016

J. Chem. Inf. Model.

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“…Indole derivatives are known to exhibit activities such as antitumour (Andreani et al, 2001); antiviral (Kolocouris et al, 1994) and anti-hepatitis C virus (Andreev et al, 2015). Indoles have attracted much attention because of their wide variety of applications especially in medicinal field.…”

Section: Structure Descriptionmentioning

confidence: 99%

5-Benzoyl-2-(5-bromo-1H-indol-3-yl)-4-(4-nitrophenyl)-1H-pyrrole-3-carbonitrile dimethyl sulfoxide monosolvate

et al. 2016

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The title compound, C26H15BrN4O3·C2H6OS, contains five rings. The indole unit is essentially planar [maximum deviation = 0.0067 (1) Å for the N atom]. The central pyrrole ring makes dihedral angles of 44.1 (2) and 51.3 (2)° with the pendant indole ring system and the nitrobenzene ring, respectively. The benzene ring is inclined with the central pyrrole ring by 51.9 (3)°. In the crystal, N—H...O hydrogen-bonding interactions between aromatic-H-atom donors and sulfoxide-O-atom acceptors result in the formation of inversion dimers with anR42(16) ring motif. The molecules are further linked into chains running along thecaxis by N—H...O, C—H...O and C—H...N hydrogen bonds.

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“…piperidine, 2-(1-adamantyl-2-methyl)pyrrolidine, and many others [77][78][79][80][81][82][83][84][85] (as reviewed by Lagoja and De Clercq 86 ). 87 In all cases, the anti-influenza A virus activity noted for these compounds compared favorably to that of amantadine when evaluated under the same experimental conditions.…”

Section: New Adamantanamine (Amantadine) Derivatives: Still Potentialmentioning

confidence: 99%

Another ten stories in antiviral drug discovery (part C): “Old” and “new” antivirals, strategies, and perspectives

Clercq

2009

Medicinal Research Reviews

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The ten stories told here deal with (i) ribavirin as an inhibitor of IMP dehydrogenase and (ii) ribavirin, in combination with pegylated interferon, as the present "standard of care" for hepatitis C; (iii) S-adenosylhomocysteine hydrolase inhibitors as antiviral agents; (iv) new adamantadine derivatives for the treatment of influenza A virus infections; (v) 5-substituted 2'-deoxyuridines (i.e. IDU, TFT) for the treatment of herpes simplex virus (HSV) infections; (vi) acyclic guanosine analogues (e.g. acyclovir) for the treatment of HSV infections; (vii) OMP decarboxylase inhibitors (i.e. pyrazofurin) and CTP synthetase inhibitors (i.e. cyclopentenylcytosine) as possible antiviral agents; (viii) the future of cidofovir (and alkoxyalkyl esters thereof) and ST-246 as potential antipoxvirus agents; (ix) the two decade journey from tivirapine to rilpivirine in the ultimate therapy of HIV infections; and (x) the extension of the therapeutic application of tenofovir disoproxil fumarate (Viread) to the treatment of hepatitis B virus infection, in addition to HIV infection.

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Synthesis and Antiviral Activity Evaluation of Some Aminoadamantane Derivatives

Cited by 120 publications

References 20 publications

Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations

Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations

5-Benzoyl-2-(5-bromo-1H-indol-3-yl)-4-(4-nitrophenyl)-1H-pyrrole-3-carbonitrile dimethyl sulfoxide monosolvate

Another ten stories in antiviral drug discovery (part C): “Old” and “new” antivirals, strategies, and perspectives

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