Chalcone derivatives: synthesis, in vitro and in vivo evaluation of their anti-anxiety, anti-depression and analgesic effects

Abstract

Anxiety disorders, depression and pain are highly prevalent pathologies. Their pharmacotherapy is associated with unwanted side effects; hence there is a clinical need to develop more effective drugs with fewer adverse reactions.Chalcones are one of the major classes of naturally occurring compounds. Chalcones and their derivatives have a huge importance in medicinal chemistry, displaying a wide range of pharmacological activities including anti-inflammatory, antimicrobial, antioxidant, cytotoxic and antitumor actions.The aim of this work was to evaluate chalcone effects on different targets involved in these pathologies. We have synthesized a series of simple chalcone derivatives taking common structural requirements described in literature related to their anxiolytic-like, antidepressant-like and/or antinociceptive properties into account.Furthermore, their potential in vitro effects towards different targets involved in these pathologies were evaluated. We have obtained twenty chalcones with moderate to high yields and assessed their ability to bind distinctive receptors, from rat brain homogenates, by displacement of labelled specific ligands: [3H] FNZ (binding site of benzodiazepines/GABAA), [3H] 8-OH-DPAT (serotonin 5-HT1A) and [3H] DAMGO (μ-opioid). Those compounds that showed the better in vitro activities were evaluated in mice using different behavioural tasks. In vivo results showed that 5′-methyl-2′-hydroxychalcone (9) exerted anxiolytic-like effects in mice in the plus maze test. While chalcone nuclei (1) revealed antidepressant-like activities in the tail suspension test. In addition, the novel 5′-methyl-2′-hydroxy-3′-nitrochalcone (12) exhibited antinociceptive activity in acute chemical and thermal nociception tests (writhing and hot plate tests). In conclusion, chalcones are thus promising compounds for the development of novel drugs with central nervous system (CNS) actions.

(E)-1-(4-Hydroxyphenyl)-3-(substituted-phenyl) prop-2-en-1-ones: Synthesis, In Vitro Cytotoxic Activity and Molecular Docking Studies

“…For this reason, the synthesis of target compounds was achieved by the condensation of para-hydroxyacetophenone with benzaldehyde using sodium hydroxide as a condensing agent. These compounds 2-11 were confirmed by using mass (MALDI-TOF-MS), FT-IR, elemental analysis, 1 H, 13 C-APT NMR spectroscopy.…”

“…All aldehydes and solvents used in the present study were provided by Sigma-Aldrich and Merck. 1 H and 13 C-APT NMR spectra, infrared analysis and microanalysis were acquired using a Bruker DPX-400 MHz spectrometer, a Perkin Elmer FT-IR spectrometer and a LECO 932 CHNS-O apparatus, respectively. A Bruker microflex LT MALDI-TOF MS spectrometer was used to obtain mass spectra.…”

“…FT-IR (KBr) ν max (cm -1 ): 3307 ν OH , 3028 and 3067 ν Ar-CH , 2827 and 2929 ν Aliphatic-CH , 1639 ν C=O , 1505, 1544, 1583, and 1613 ν C=C . 1 H NMR (DM-SO-d 6 ) δ 3.83 (3H, s, H 18 (-OCH 3 )), 3.88 (3H, s, H 19 (-OCH 3 )), 3.91 (3H, s, H 17 (-OCH 3 )), 6.76 (1H, s, H 13 ), 6.90-6.92 (2H, d, J = 8.4 Hz, Ar-H…”

“…Chalcone is an important chemo type that has attracted great research interest for decades due to the abundant natural chalcone-based compounds, the easy synthesis and derivatization, and most importantly, the diverse biological activities of various chalcone-based compounds. [1][2][3][4][5][6] The well documented biological activities of chalcones include anti-HIV, 7 antibacterial, 8 anti-cancer and antioxidant, [9][10][11] antituberculosis agents, 12 anti-prolif-erative, 13 antiplatelet, 14,15 and antimalarial. 16,17 Numerous studies have attempted to elucidate the mechanisms of action and target interactions responsible for these biological activities.…”

Synthesis, Crystal Structures, and Molecular Properties of Three Nitro-Substituted Chalcones

“…Naturally occurring chalcones are multisubstituted in the aryl rings by different groups, mainly hydroxyl, methoxy and alkenyl functions, while their synthetic analogs contain one or more aryl substituents such as halogens, alkyl, amine-, nitro-, nitril-, acetamide-, carboxylic groups, heterocyclic, benzene and condensed rings, etc [1][2][3][4]. Among these synthetic derivatives, the nitrochalcones have generated continuous interest among chemists and biochemists, mainly because of their applications in medicinal chemistry as potential antimicrobial, antihyperglycemic, antinociceptive, antitumor tools [5][6][7][8][9][10][11][12][13]. In this sense, in a previous report, we synthesized three nitro-substituted chalcones and evaluated their anti-inflammatory activity.…”