mannich-bases and lawsone

A series of new lawsone Mannich bases derived from salicylaldehydes or nitrofurfural were prepared and tested for their activities against Leishmania major, Toxoplasma gondii, and Trypanosoma brucei brucei parasites. The hydrochloride salts 5a and 6a of the Mannich bases 2a and 3a, derived from unsubstituted salicylaldehyde and long-chained alkyl amines, were selectively and strongly active against T. gondii cells and appear to be new promising drug candidates against this parasite. Compound 6a showed an even higher activity against T. gondii than the known lawsone Mannich base 1b. Compound 4a, derived from salicylaldehyde and 2-methylaminopyridine, was also distinctly active against T. gondii cells. The derivatives 3a (salicyl derivative), 3b (3,5-dichloro-2-hydroxyphenyl derivative), and 3d (5-nitrofuranyl derivative) as well as the hydrochlorides 6a and 6b were also efficacious against T. b. brucei cells with compounds 3a and 3b being more selective for T. b. brucei over Vero cells when compared with the known control compound 1b. The derivatives 5a, 5c, 6a, and 6c proved to be up to five times more active than 1b against L. major promastigotes and up to four times more efficacious against L. major amastigotes.

Topics: Antiparasitic Agents; Dose-Response Relationship, Drug; Leishmania major; Mannich Bases; Molecular Structure; Naphthoquinones; Parasitic Sensitivity Tests; Structure-Activity Relationship; Toxoplasma; Trypanosoma brucei brucei

Topics: Albumins; Algorithms; Coordination Complexes; Ligands; Mannich Bases; Metals; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Naphthoquinones; Protein Binding; Spectrum Analysis; Thermodynamics

Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cytoskeleton; Drug Design; Entamoeba histolytica; Humans; Inhibitory Concentration 50; Mannich Bases; Naphthoquinones; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma brucei brucei

Zinc(II) and copper(II) complexes of a tridentate Mannich base L1 derived from 2-hydroxy-1,4-naphthoquinone, pyridinecarboxyaldehyde and 2-aminomethylpyridine, [ZnL1Cl(2)]·H(2)O 1 and [CuL1Cl(2)]·2H(2)O 2, have been synthesized and fully characterized. The structure of complex 1 has been elucidated by a single crystal X-ray diffraction study: the zinc atom is pentacoordinate and the coordination geometry is a distorted square base pyramid, with a geometric structural parameter τ equal to 0.149. Vibrational spectroscopy and ab initio DFT calculations of both compounds have confirmed that the two complexes exhibit similar structures. Full assignment of the vibrational spectra was also supported by careful analysis of the distorted geometries generated by the normal modes.

Topics: Coordination Complexes; Copper; Crystallography, X-Ray; Electron Spin Resonance Spectroscopy; Electrons; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Mannich Bases; Models, Molecular; Molecular Conformation; Naphthoquinones; Quantum Theory; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Thermodynamics; Vibration; Zinc