Synthesis and structural analysis of copper(II) pyridine amide complexes as HIV-1 protease inhibitors

Lebon, Florence; Ledecq, Marie; Benatallah, Zohra; Sicsic, Sames; Lapouyade, R.; Kahn, Olivier; Garçon, Arnaud; Reboud‐Ravaux, Michèle; Durant, François

doi:10.1039/a809270b

Cited by 16 publications

(15 citation statements)

References 13 publications

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“…The overall geometry of 9 is distorted square pyramidal with an O1-Cu-Cl1 angle of 161.49(4)° and an O2-Cu-N2 angle of 176.02(6)°. The Cu-O (metal-water) bond distance of is close to that found in other complexes [1,31,40]. Complex 10, which is the only cobalt (II) complex in the set, has tetrahedral geometry with one bidentate ligand and two directly bound chloride anions (2.2340 (7) and 2.500(7) Å).…”

Section: Synthesis and Characterizationsupporting

confidence: 73%

“…A distinctive characteristic of these complexes is that the carbonyl bond distances in the bound ligands have increased, by as much as +0.04 Å, and the amide bond distances have decreased by as much as −0.04 Å. Bond distances for the donor-metal atoms are similar to those in the copper (II) complexes reported by Lapouyade [30], Lebon [1,31], and Choi [32]. 4 , which has no spacer between the amide function and the pyridine ring.…”

Section: Synthesis and Characterizationsupporting

confidence: 71%

“…4 , which has no spacer between the amide function and the pyridine ring. The copper (II) complex Cu(DMABA-MP) 2 (ClO 4 ) 2 ·3H 2 O, which has a similar ring size displays a comparable bite angle (89.17(6)°) [31]. Complexes 4, 6, 7, and 11 exhibit hydrogen-bonding between the amide protons and one oxygen atom of a perchlorate anion (or fluorine atoms of a hexafluorophosphate anion in the case of 7) while 1 shows hydrogen bonding between the amide protons and adjacent methanol molecules in the lattice.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

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Metal complexes of 3-thiophene carboxamides containing a pyridine ring

Howell

Day

Noftle

2007

Inorganica Chimica Acta

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Complexes of Zn(II), Cu(II) and Co(II) with either N-(2-methylpyridyl)-3-thienyl-alkylcarboxamide or N-(2-pyridyl)-3-thienylalkyl-carboxamide groups have been prepared and characterized. Crystal structures of ten new complexes are reported and discussed. N-(2-Methylpyridyl)-3-thienyl-alkyl-carboxamide exhibits both uni-and bidentate behavior. With all ligands, bidentate complexation is through the carbonyl oxygen and pyridine nitrogen atoms (O, N) and the amide nitrogen atom remains protonated. The electrochemical behavior and the infrared spectra of selected complexes are discussed.

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Section: Synthesis and Characterizationsupporting

confidence: 73%

Section: Synthesis and Characterizationsupporting

confidence: 71%

Section: Synthesis and Characterizationmentioning

confidence: 99%

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Metal complexes of 3-thiophene carboxamides containing a pyridine ring

Howell

Day

Noftle

2007

Inorganica Chimica Acta

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“…Novel irreversible inhibitors containing sulfonamide and sulfone as amide bond isosteres were designed and displayed rapid, timedependent inactivation of HIV-1 protease in the nanomolar range, with high potency in cell culture [140]. New copper coordination compounds, having an octahedral geometry favorable for the orientation of their interacting substituents within the protease subsites were designed and inhibited HIV-1 protease in the micromolar range (as exemplified by complex 27) [127].…”

Section: Biostructural Approach or "Rational Drug Design"mentioning

confidence: 99%

“…This variant enzyme, which had virtually the same three-dimensional structure and specific activity as the wild-type protein, was not inhibited by copper and mercury. Only in the presence of exogenous chelating agents such as dithiothreitol [168], ascorbic acid [169], bathocuproine disulfonic acid [170] or carboxamide ligands [126,127] was inhibition recovered. In those particular cases, it was again postulated that the synthetic protease was inactivated via a competitive inhibition pattern, by the so-formed metal-organic complexes.…”

Section: Heterodimer Formationmentioning

confidence: 99%

Approaches to the Design of Effective HIV-1 Protease Inhibitors

Lebon¹,

Ledecq

2000

CMC

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Recently, western countries have recorded a decrease in the death rate imputed to AIDS. This success has been largely attributed to the presence on the market of chemotherapies that inhibit the infectivity of the predominant causative agent, the HIV-1 virus, by targeting essential viral enzymes. One of these is the protease (HIV-1 PR) whose activity is a prerequisite for viral replication. Two main sites have been identified as potential targets for the inhibition of HIV-1 PR, the active site and the interface, the latter being largely responsible for the stabilization of the enzyme dimeric structure. The compounds that have reached clinical application so far target the active site of HIV-1 PR. These molecules act as transition state analogues and result from modifications of the peptidic scaffold into peptidomimetics. In order to improve their bioavailability, systematic biological screening and de novo design have been used to suggest new non-peptide inhibitors combining both antiviral potency and favorable pharmacokinetic properties. In parallel, compounds targeting other potential sites of inhibition have been tested. Peptides and peptidomimetics based on the terminal sequence of the enzyme, a site which is proposed to be less susceptible to mutations, have been shown to lead to HIV-1 PR inactivation. Cupric ion was described to bind a sequence on the protease surface, which includes cysteine and histidine residues, leading to the inhibition of the enzyme. In the future, these non-active site inhibitors could provide an alternative in anti-HIV drug combination strategies.

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