Synthesis (Z) vs (E) Selectivity, Antifungal Activity against Fusarium oxysporum, and Structure-Based Virtual Screening of Novel Schiff Bases Derived from l-Tryptophan

Abstract

Schiff bases are widely used molecules due to their potential biological activity. In this manuscript, we presented the synthesis and NMR study of new enamine Schiff bases derived from l -tryptophan, showing that the Z-form of the enamine is the main tautomeric form for aliphatic precursors. The DFT-B3LYP methodology at the 6-311+G**(d,p) level suggested that the tautomeric imine forms are less stable than the corresponding enamine forms. Their isomerism depends on the formation of intramolecular hydrogen bonds and steric factors associated with the starting carbonyl precursors. The in vitro biological activity tests against Fusarium oxysporum revealed that acetylacetone derivatives are the most active agents (IC 50 < 0.9 mM); however, the antifungal activity could be disfavored by bulky groups on ester and enamine moieties. Finally, the structure-based virtual screening through molecular docking and MM-GBSA rescoring revealed that Schiff bases 3e , 3g , and 3j behave putatively as binders for target proteins involved in the life processes of F. oxysporum . In this sense, molecular dynamics analysis showed that the ligand–protein complexes have good stability with root-mean-square deviation (RMSD) values within the allowed range. Therefore, the present study paves the way for designing new antifungal compounds based on l -tryptophan-derived Schiff bases.

1,3,4-Oxadiazole derivatives as potent antifungal agents: Synthesis, biological evaluation and an in silico study

“…In addition, the benzimidazole ring exhibited stacking interactions with some key amino acids such as Cys239, Leu253, Ala248, and Ala314 and the 1,3,4-oxadiazole ring showed common features when interacting with the amino acid Leu246, Lys350 and Thr179. These key amino acids have been proven to be crucial in determining the activity of the ligand toward the examined β-tubulin target (Li et al, 2019;Zhang et al, 2020;Borrego-Muñoz et al, 2022). This result is very promising for the development of β-tubulin inhibition compounds based on the 1,3,4oxadiazole/benzimidazole structure.…”

Anti-Inflammatory Effect of Izalpinin Derived from Chromolaena leivensis: λ-Carrageenan-Induced Paw Edema and In Silico Model

“…Molecular docking was performed with the Glide software (Schrödinger, LLC, New York, NY, USA, 2020), using the standard precision (SP) mode, that uses hierarchical filters to find the best ligand poses in the protein binding site. The filters incorporate a systematic search of orientation space, positional and conformational, of the ligands before assessing the energetic interaction with the protein [34]. All docking were re-scored by binding free energy calculations using the MM-GBSA (molecular mechanics combined with the generalized Born surface area) method.…”

“…In both equilibrium and production MDs, temperature and pressure were kept constant at 300 K and 1.01325 bar, respectively, by coupling to a Nose-Hoover [38] thermostat method with a relaxation time of 1 ps and Martyna-Tobias-Klein barostat [39] to keep the pressure constant with an integration time of 2 ps. Trajectories were monitored using geometric properties throughout the simulation time; the most common measure of these deviations or structural fluctuations over time is made by calculating the root-mean-square deviation (RMSD) and root mean square fluctuation (RMSF) [34]. The simulations were analyzed with Desmond and VMD [40].…”

Manganese(II) and Zinc(II) metal complexes of novel bidentate formamide-based Schiff base ligand: synthesis, structural characterization, antioxidant, antibacterial, and in-silico molecular docking study

“…Schiff base ligands containing nitrogen, along with other donor atoms such as oxygen and sulfur in their molecular structures, serve as chelating agents and easily form complexes with various metal ions ( Abd El Wahed et al, 2004 ; Mishra et al, 2005 ; El-Sherif and Eldebss, 2011 ). In recent years, these complexes gained significant attention due to their diverse use in biology ( Ghanghas et al, 2021 ), as models for metal-containing sites in metalloproteins ( Ueno et al, 2004 ; Shahraki, 2022 ), catalysts for some organic reactions ( Juyal et al, 2023a ), and complexing ability toward some toxic metals ( Vaghasiya et al, 2004 ) encompassing antibacterial ( Kargar et al, 2021 ; Muthukumar et al, 2022 ), antifungal ( Joshi et al, 2020 ; Shiryaev et al, 2021 ; Borrego-Muñoz et al, 2022 ), anticancer ( Tadele and Tsega, 2019 ; Aslan et al, 2020 ; Alorini et al, 2022 ), antioxidant ( Buldurun et al, 2019 ; Bingöl and Turan, 2020 ; Yadav et al, 2021 ), anti-inflammatory ( Devi et al, 2019 ; Krishna et al, 2023 ), and antiviral activities ( Abd El-Hamid et al, 2023 ; Bhandarkar et al, 2023 ).…”