Victor Facchinetti

Synthesis, antimalarial evaluation and molecular modeling studies of hydroxyethylpiperazines, potential aspartyl protease inhibitors, Part 2.

The antimalarial acitivity of hydroxyethylamines, synthesized from the reaction of intermediated hydroxyethypiperazines with benzenesulfonyl chlorides or benzoyl chlorides, has been evaluated in vitro against a W2 Plasmodium falciparum clone. Some of the nineteen tested derivatives showed a significant activity in vitro, thus turning into a promising new class of antimalarials. In addition, a molecular modeling study of the most active derivative (5l) was performed and its most probable binding modes within plasmepsin II enzyme were identified.

Synthesis and Antimycobacterial Activity of 2-aryl-3-(arylmethyl)-1,3- thiazolidin-4-ones

Fifteen new heterocyclic thiazolidinones have been synthesized from one-pot reactions of piperonylamine, are- nealdehydes and mercaptoacetic acid. These compounds plus ten 2-aryl-3-(benzyl)-1,3-thiazolidin-4-ones which had been previously synthesized, were evaluated as antibacterial agents against Mycobacterium tuberculosis H37Rv using the Alamar Blue susceptibility test and their activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. Six of the series exhibited modest activity when compared to the first line drugs such as isoniazid (INH) and rifampicin (RIP). Therefore this class of compounds could be a good starting point to develop new lead compounds in the treatment of multi-drug resistant tuberculosis.

Perspectives on the Development of Novel Potentially Active Quinolones Against Tuberculosis and Cancer

Quinolones and its derivatives comprise an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, antitumor, antiviral, anti-ischemic, antiparasitic and anxiolytic. Persistent efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side-effects. The present review aims to highlight some recent discoveries on the development of novel quinolone-based compounds with potential antitubercular and anticancer activity.

3-(2H-1,3-Benzodioxol-5-ylmeth­yl)-2-(2-meth­oxy­phen­yl)-1,3-thia­zolidin-4-one

The title molecule, C18H17NO4S, features a 1,3-thiazolidine ring that is twisted about the S—C(methylene) bond. With reference to this ring, the 1,3-benzodioxole and benzene rings lie to either side and form dihedral angles of 69.72 (16) and 83.60 (14)°, respectively, with the central ring. Significant twisting in the molecule is confirmed by the dihedral angle of 79.91 (13)° formed between the outer rings. Linear supramolecular chains along the a-axis direction mediated by C—H⋯O interactions feature in the crystal packing.

Crystal structures of 3-(2H-1,3-benzodioxol-5-ylmethyl)-2-(m- and p-nitrophenyl)-1,3-thiazolidin-4-ones: different roles of the oxygen atoms

Abstract The crystal structures of two isomeric 3-(2H-1,3-benzodioxol-5-ylmethyl)-2-(aryl)-1,3-thiazolidin-4-one compounds (1: aryl=4-O2NC6H4; 2: aryl=3-O2NC6H4) are reported. In both these nonplanar, compounds, the carbonyl oxygen is involved in intramolecular C–H···O hydrogen bonds. However, there are significant differences in the sets of intermolecular interactions, in particular the roles of the oxygen atoms, exhibited by the two compounds. Thus in 1, a dioxolyl oxygen and the two nitro group oxygen atoms are each involved in different chain forming C–H···O intermolecular hydrogen bonds, while the carbonyl oxygen atom is not involved in any intermolecular interaction. In 2, the dioxolyl oxygen atom is involved in the formation of centrosymmetric dimers, the carbonyl oxygen in three different C–H···O hydrogen bonds and the nitro group oxygens in two N–O···π(aryl) interactions. Compound 2 exhibits also C–H···π(phenyl), π(phenyl)···π(phenyl) and π(benzodioxolyl)···π(benzodioxolyl) interactions, while in 1 only the latter interaction is present. Compound 1 crystallizes in the monoclinic space group, P21/a with Z=4, while compound 2 crystallizes in the triclinic space group, P1̅, with Z=2.

Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Antibacterial Activity of Thioetherhydroxyethylsulfonamide Derivatives

Thioetherhydroxyethylsulfonamide derivatives were synthesized and evaluated for their in vitro antibacterial activity against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and Staphylococcus aureus (ATCC 25923). Results have shown that compounds 8c and 9e display potent activity (MIC = 0.125 µg/mL) against E. coli when compared with the standard drug sulfamethoxazole (SMZ, MIC < 0.5 µg/mL) for this same strain. All the new compounds were fully identified and characterized by NMR ((1)H and (13)C) and X-ray crystallography (for compound 8c). This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight against multi-drug bacterial resistance.