Christiane Santelli-Rouvier

Membrane permeation by multidrug-resistance-modulators and non-modulators: effects of hydrophobicity and electric charge.

This study was designed to test the hypothesis that lipophilic cationic drugs with only roughly similar structures mediate the reversal of multidrug‐resistance (MDR) by interacting with membrane phospholipids. The permeation properties of MDR‐modulators and non‐modulators were studied by quantifying their ability to induce the leakage of Sulphan blue through the membrane of negatively charged unilamellar liposomes.

Synthesis of aza mono, bi and tricyclic compounds. Evaluation of their anti MDR activity

Anti MDR activity of a series of acridine, pyridoquinoline, quinoline and pyridine analogous amines was evaluated. Interesting activity is displayed by tricyclic compounds. Besides ring size, influence of the side chain was studied.

Dihydroethanoanthracene Derivatives as In Vitro Malarial Chloroquine Resistance Reversal Agents

ABSTRACT The ability of four 9,10-dihydroethanoanthracene derivatives (BG920, BG932, BG958, and BG996), as well as verapamil and promethazine, to reverse chloroquine resistance was assessed against 24 chloroquine-resistant and 10 chloroquine-susceptible strains of Plasmodium falciparum from different countries. The 9,10-dihydroethanoanthracene derivatives clearly increase chloroquine susceptibility only in chloroquine-resistant isolates.

Effects of a series of dihydroanthracene derivatives on drug efflux in multidrug resistant cancer cells

A set of 9,10-dihydro-9,10-ethano and ethenoanthracene derivatives was tested with the aim to quantify the effect observed on drug efflux. Structure activity relationships and molecular modeling studies allowed to define topological display of pharmacophoric groups for these reversal agents.

In Vitro Increase in Chloroquine Accumulation Induced by Dihydroethano- and Ethenoanthracene Derivatives in Plasmodium falciparum-Parasitized Erythrocytes

ABSTRACT The effects of a series of dihydroethano- and ethenoanthracene derivatives on chloroquine (CQ) accumulation in CQ-susceptible strain 3D7 and CQ-resistant clone W2 were assessed. The levels of CQ accumulation increased little or none in CQ-susceptible strain 3D7 and generally increased markedly in CQ-resistant strain W2. At 10 μM, 28 compounds yielded cellular accumulation ratios (CARs) greater than that observed with CQ alone in W2. At 10 μM, in strain W2, 21 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 15 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 13 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 9 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 μM, 17 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 12 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 6 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 3 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 μM, 17 of 31 compounds were more potent inducers of CQ accumulation than verapamil and 12 of 31 compounds were more potent inducers of CQ accumulation than promethazine. The nature of the basic group seems to be associated with increases in the levels of CQ accumulation. At 1 and 10 μM, 10 of 14 and 13 of 14 compounds with amino group (amines and diamines), respectively, had CARs ≥3, while at 1 and 10 μM, only 1 of the 13 derivatives with amido groups had CARs ≥3. Among 12 of the 31 compounds which were more active inducers of CQ accumulation than promethazine at 1 μM, 10 had amino groups and 1 had an amido group.

Synthesis of the tertiaryphosphine derivatives of iron carbonyl phosphines: preparation of tetracarbonyl[tris(2-furyl)phosphine]iron(0), pentacarbonylbis[μ-bis(2-furyl)phosphido]-[tris(2-furyl)phosphine]diiron(0), tetracarbonyl[tris(2-benzofuryl) phosphine]iron(0) and pentacarbonylbis[μ-bis(2-benzofuryl) phosphido]-[tris(2-benzofuryl) phosphine]diiron-(0)

Abstract Pentacarbonyl iron reacts with tris(2-furyl)phosphine (or tris(2-benzofuryl)phosphine) in the presence of sodium borohydride in refluxing n -butanol to give the title compounds. The crystal and molecular structure of pentacarbonylbis[μ-bis(2-furyl)phosphido] [tris(2-furyl)phosphine]diiron(0) were determined by X-ray crystallography.

Polymorphism in Plasmodium falciparum Drug Transporter Proteins and Reversal of In Vitro Chloroquine Resistance by a 9,10-Dihydroethanoanthracene Derivative

ABSTRACT BG958 reverses resistance in chloroquine-resistant isolates from different countries. Five mutations in the Plasmodium falciparum crt (pfcrt) gene resulting in the amino acid changes K76T, M74I, N75E, A220S, and R371I are systematically identified in resistance-reversed Asian, African, and Brazilian parasites which possess the pfcrt (CIET) haplotype. In combination with BG958, the activity of chloroquine is increased in parasites with the N86Y mutation in pfmdr1.

The crystal and molecular structures of 9,10-dihydro-9, 10-ethano- and etheno-anthracenes

As part of our investigation on histamine receptor antagonists, the structures of two 9-10-dihydroanthracene derivatives are reported: 4: C22H28N2; hexagonal, P61; a = 10.014(1), c = 34.556(7) Å; V = 3001.0(7)Å3; and Z = 6; 9:C19H19N: triclinic, P-1; a = 8.427(2), b = 12.806(3), c = 15.292(3) Å, α = 70.27(3), β = 80.83(3), γ = 72.98(3)°; V = 1482.0(6) Å3; and Z = 4. All non-aromatic rings in both molecules adopt a similar conformation. However, the three six-membered rings in the etheno-anthracene structure adopt a more regular boat form in spite of two sp2 carbon bridged atoms.

A convenient synthesis of the (±)-prelog-djerassi lactone from cyclopentanone

Abstract The stereoselective addition of crotyl Grignard reagent to 2-alkylidene-5-methylcyclopentanones followed by dehydration, 1,4-reduction of the triene, ozonolysis and Baeyer-Villiger oxidation afforded a δ-lactone (28 % of overall yield), well-known precursor of the Prelog-Djerassi Lactone.

Palladium-mediated cyclization of 1,5-hexadien-3-ols to 1-methyl-1,3-cyclopentadienes

Abstract Treatment of 1-allyl-2-alkenylidenecyclohexanols in acetic acid by the Pd(0) complex [Pd(Ph 3 P) 4 ] led to 8-methyl bicyclo[4.3.0]nona-1(6),7-dienes. In contrast, only few examples of cyclization vs elimination were observed in acyclic 1,5-hexadien-3-ols.