Synthesis and Antifungal Activity against Fusarium oxysporum of Some Brassinin Analogs Derived from l-tryptophan: A DFT/B3LYP Study on the Reaction Mechanism

Abstract

An efficient methodology to obtain novel antifungal analogs of brassinin 1 is described. Starting from L-tryptophan 2, N,N -dialkylthiourea 4, 4-[(1H-indol-3-yl)methylene]-2-sulfanylidene-1,3-thiazolidin-5-one 5 and alkyl (2S)-3-(1H-indol-3-yl)-2-{[(alkylsulfanyl)carbonothioyl]amino} propanoate 6 type compounds were obtained as main products in different ratios depending on the reaction conditions via a tandem dithiocarbamate formation and Michael addition reaction. In order to understand the dependence of the reaction conditions on the mechanism pathway, a DFT/B3LYP study was performed. The results suggested the existence of competitive mechanistic routes which involve the presence of an ionic dithiocarbamate intermediate 9. Antifungal activities of all products were then evaluated against Fusarium oxysporum through mycelial growth inhibition using a microscale amended-medium assay. IC 50 values were thus determined for each compound. These results showed that 6-related compounds can be considered as promissory antifungal agents.

Solvent Free Three-Component Synthesis of 2,4,5-trisubstituted-1H-pyrrol-3-ol-type Compounds from L-tryptophan: DFT-B3LYP Calculations for the Reaction Mechanism and 3H-pyrrol-3-one↔1H-pyrrol-3-ol Tautomeric Equilibrium

“…Esterification reactions of L -tryptophan were carried out employing Li and Sha methodology [ 27 ] with some modifications [ 28 ]. Mixtures of L -tryptophan (1 eq.…”

Indole-Containing Phytoalexin-Based Bioisosteres as Antifungals: In Vitro and In Silico Evaluation against Fusarium oxysporum

“…In order to estimate such tendencies experimentally and compare them with the performance of the present docking study, the mycelial growth inhibition was evaluated for all compound set against F. oxysporum. Such evaluation was built on our prior study to expand the search for promising antifungal agents [8] and the resulting half-maximal inhibitory concentrations (IC 50 ) are exposed in Table S4. Test compounds exhibited mycelial growth inhibition at different levels, but some NNDATU, OPD-DTC and CE-DTC exhibited the lowest IC 50 values (<0.8 mM), thus, they can be considered as the best antifungals within the experimental dataset.…”

“…Twenty-one indole-containing phytoalexin analogs and four L-tryptophan alkyl esters (1-25) were synthesized through the previously reported protocol [8] ( Figure S1) and they were chosen as test compounds (Figure 1). These structures were 3D-sketched and organized according to close-related moieties affording seven substituted groups such as 2-alkyl aminoesters (1-4), N,N-dialkylthioureas (5-8), 2-cyanoethyl N-alkyldithiocarbamates (9-12), 3-methoxy-3-oxopropyl N-alkyldithiocarbamate (13-16), 2-methyl-4-oxopentan-2-yl N-alkyldithiocarbamate (17)(18)(19)(20), 2-oxo-1,3-diphenylpropyl N-alkyldithiocarbamates (21-24) and 4-[(1H-indol-3-yl)-methylene]-2-sulfanylidene-1,3-thiazolidin-5-one (25).…”

“…Compounds 1-25 were evaluated for their antifungal activity against F. oxysporum following the previously reported amended-medium protocol to assess the in-vitro mycelial growth inhibition [8]. The activity was expressed as half-maximal inhibitory concentrations, IC 50 (in mM), obtained after non-linear regression using the program GraphPad Prism version 5.00 (GraphPad Software, San Diego, CA, USA).…”

“…Their IUPAC names are displayed in the complementary material (Table S1). Such compounds were then chosen as test compounds owing to their antifungal activity by inhibiting mycelial growth of F. oxysporum [8,9]. Thus, in order to explore Molecules 2020, 25, 45 3 of 19 and outline a further information related to the potential and putative targets of these compounds at in silico level, docking simulations were therefore performed with 25 fungal enzymes (E1-E25) (Table A1 (Appendix A)), which were selected due to their significant associations on pathogenic and metabolic performance of Fusarium spp.…”