Application of the Morita-Baylis-Hillman reaction in the synthesis of 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones as potential HIV-1 integrase inhibitors.

A practicable six-step synthetic pathway has been developed to access a library of novel 3-[(N-cycloalkylbenzamido)methyl]-2-quinolones using Morita-Baylis-Hillman methodology. These compounds and their 3-[(N-cycloalkylamino)methyl]-2-quinolone precursors have been screened as potential HIV-1 integrase (IN) inhibitors. A concomitant survey of their activity against HIV-1 protease and reverse-transcriptase reveals selective inhibition of HIV-1 IN.

Heteroditopic P,N ligands in gold(I) complexes: synthesis, structure and cytotoxicity.

New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT=tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp(3)-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I).

Novel furocoumarins as potential HIV-1 integrase inhibitors.

A series of seven novel, rationally designed N-substituted 3-{3,5-dimethylfuro[3,2-g]coumarin-6-yl}propanamides have been prepared as potential HIV-1 integrase (IN) inhibitors via a five-step pathway commencing with resorcinol and diethyl 2-acetylglutarate, and the HIV-1 IN inhibition potential of these compounds has been examined relative to raltegravir, a known HIV-1 IN inhibitor.

Gold-phosphine binding to de novo designed coiled coil peptides.

The coordination of the therapeutically interesting [AuCl(PEt(3))] to the de novo designed peptide, TRIL23C, under aqueous conditions, is reported here. TRIL23C represents an ideal model to investigate the binding of [AuCl(PEt(3))] to small proteins in an effort to develop novel gold(I) phosphine peptide adducts capable of mimicking biological recognition and targeting. This is due to the small size of TRIL23C (30 amino acids), yet stable secondary and tertiary fold, symmetric nature and the availability of only one thiol binding site.

Modification of HIV-1 reverse transcriptase and integrase activity by gold(III) complexes in direct biochemical assays.

Gold(I) and gold(III) complexes have been previously investigated for potential biomedical applications including as anti-HIV agents. The oxidising nature of some gold(III) complexes yields well-documented cellular toxicity in cell-based assays but the effect in direct biochemical assays has not been fully investigated. In this study, gold(III) complexes were evaluated in HIV-1 reverse transcriptase and HIV-1 integrase biochemical assays.

{μ-1,2-Bis[bis(4-meth-oxy-phen-yl)phosphan-yl]-1,2-dimethyl-hydrazine-κP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(30)H(34)N(2)O(4)P(2))]·2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two almost linearly coordinated gold(I) atoms [P-Au-Cl = 175.68 (3) Å]. The nuclei are 3.

{μ-1,2-Bis[bis-(4-meth-oxy-phen-yl)phosphan-yl]-1,2-diethyl-hydrazine-κP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(32)H(38)N(2)O(4)P(2))]·2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two linear gold(I) nuclei [P-Au-Cl = 175.98 (3)°]. The nuclei are 3.

[μ-1,2-Bis(diphenyl-phosphan-yl)-1,2-diethyl-hydrazine-κP:P']bis-[chlorido-gold(I)] tetra-hydro-furan disolvate.

The title compound, [Au(2)Cl(2)(C(28)H(30)N(2)P(2))]·2C(4)H(8)O, was synthesized from a bidentate phosphine ligand complexed to two linear gold(I) chloride moieties. The Au(I) atom is in an almost linear coordination with a P-Au-Cl angle of 179.22 (4)°.

Poly[[μ(2)-1,2-bis-(diphenyl-phosphan-yl)-1,2-diethylhydrazine]-μ(4)-nitrato-μ(2)-nitrato-silver(I)].

The title compound, [Ag(2)(NO(3))(2)(C(28)H(30)N(2)P(2))](n), crystallizes in polymeric α-helices. Three O atoms from three different nitrate ions in equatorial positions and two Ag atoms at axial positions set up a trigonal bipyramid. These units are linked by the phosphine ligands into endless helical chains that run along the c axis.

μ-1,2-Bis(diphenyl-phosphan-yl)-1,2-dimethyl-hydrazine-κP:P']bis-[chlorido-gold(I).

The title compound, [Au(2)Cl(2)(C(26)H(26)N(2)P(2))], is formed from a bidentate phosphine ligand complexed to two linearly coordinated gold(I) atoms. The gold(I) atoms are 3.4873 (7) Å apart.