Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells

Abstract

In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.

Synthesis and Characterization of the Structure of Diethyl [(4-{(1H-Benzo[d]Imidazol-1-yl)Methyl}-1H-1,2,3-Triazol-1-yl)(Benzamido)Methyl]Phosphonate Using 1D and 2D NMR Experiments

“…The phosphonic α-amino acids and their derivatives has a considerable role play in the design of new drugs [1]. Thus, these derivatives have a high potential for diverse biological activity [2], acting as a protease inhibitor agent of West Nile virus [3], anticancer agent [4], antibacterial [5], antioxidant [6].…”

Cytotoxic Activity of Piperazin-2-One-Based Structures: Cyclic Imines, Lactams, Aminophosphonates, and Their Derivatives

“…It can be expected that introduction of this functionality into a nitrogen heterocycle can result in a desired biological activity [ 16 ]. Indeed, our research proved that incorporation of phosphorus functionality greatly improves antiproliferative activity of N -heterocycles obtained by our group [ 17 ]. Cytotoxicity of the products were relatively low to normal cells making them promising compounds for drug development.…”

“…Significantly better results were obtained for two derivatives: a phosphonate bearing big TADDOL—derived moiety 4e , and a monocyclic diamine with trifluoromethyl substituent 6 . Compound 4e was previously tested in our previous antiproliferative study using other cancer lines and was found as the only active compound [ 17 ]. Moreover, a mixture of epimers which was obtained from the synthesis was even more efficient in comparison with a pure enantiomer.…”

“…In our previous studies of antiproliferative activity of phosphonic derivatives of octahydroquinoxalin-2(1H)-one [ 17 ], the analysis of mechanism of their proliferation inhibition of the MV4-11 cells was performed. We found that most active compounds induce cell apoptosis associated with an increased caspase 3/7 activity.…”

Synthèse Et Caractérisation De La Structure Du [{4-[(1HBenzo[D]Imidazol-1-Yl)Méthyl]- 1H-1,2,3-Triazol-1 Yl}(Benzamido)Méthyl]Phospho nate De Diéthyle Par La Spectroscopie RMN 1D Et 2D

“…Les α-aminoacides phosphoniques et leurs dérivés occupent une place importante dans la conception de nouvelles formules de médicaments (Iwanejko et al, 2020). Ainsi, ces dérivés sont dotés d'un fort potentiel d'activité biologique intéressant et divers (Damiche et al, 2016), agissant comme agent inhibiteur de la protéase du virus Nil occidental (Skoreński et al,2019), agents anticancéreux (Fang et al, 2016), antibactériens (Tripolszky et al, 2020) et antioxydants (Nayab et al, 2020).…”