9-Fluorenon-4-carboxamides: synthesis, conformational analysis, anti-HSV-2, and immunomodulatory evaluation. Note II

Abstract

Title 9-fluorenon-4-carboxamides has been prepared as asymmetrically-substituted analogues of the antiviral tilorone and their antiherpetic and cytokine-inducing properties have been explored. The best pharmacological profiles were shown by carboxamides 1, 4, 9, and 10 endowed with anti-HSV-2, IFNα, IFNγ and TNFα-inducing properties assayed on peripheral blood mononuclear cells (PBMC). The conformational analysis of compounds 1-10 has been performed by molecular modelling techniques and a geometrical descriptor was evaluated.

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

“…For synthetic fluorenones antitumoral [9], antiviral [10], and trypanocidal [11] activities have been reported, and tilorone (1i), an antiviral fluorenone launched about 50 years ago, is presently discussed as a therapeutic option for fighting Ebola and SARS-CoV-2 viruses [12]. Modifications of the tilorone scaffold resulted in compounds having cytokine-inducing [13], antitumor [14], and telomerase-inhibitory effects [15]. Further synthetic fluorenones and polyfluoren(on)es show attractive electronic and optical properties [16][17][18][19][20][21], utilized in LEDs, semiconducting polymers, and solar cells.…”

Molecular Modeling, Synthesis, and Preliminary Biological Evaluation of Glutathione-S-Transferase Inhibitors as Potential Therapeutic Agents

“…A preliminary docking evaluation was carried out considering the total number of generated structures within 50 kJ/mol above the global minimum energy (NCONF), their distribution, and the average number of duplicate structures (AND). In our experience, an AND value equal or higher than 2 indicates a good exploration of the conformational space . According to the MOLINE method, final geometries were used for estimation of the free energy of binding Δ G (Table ).…”