Facile Syntheses and Molecular-Docking of Novel Substituted 3,4-Dimethyl-1H-pyrrole-2-carboxamide/carbohydrazide Analogues with Antimicrobial and Antifungal Properties

Abstract

The article describes the use of facile one-pot, high-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamides 3a–m and carbohydrazide analogues 5a–l as potential antifungal and antimicrobial agents. The structural identity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compounds 5h, 5i and 5j were found to be the most potent against Aspergillus fumigatus, with MIC values of 0.039 mg/mL. The compound 5f bearing a 2, 6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with a MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking with the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron-related deleterious side effects observed with many existing antifungal compounds.

Antimicrobial Peptides: Interaction With Model and Biological Membranes and Synergism With Chemical Antibiotics

“…Another “ in silico ” methodology is the molecular docking, a reliable tool able to locate the probable binding interactions of ligands with their target proteins (Bhosale et al, 2018 ). This technique is suitable for investigations related with molecular events, including ligand binding modes and the corresponding intermolecular interactions that stabilize the ligand-receptor complex.…”

Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines

“…A lot of market drugs containing pyrrole ring show different pharmacological activities, such as antipsychotics [ 4 ], antidepressants [ 5 ], anticonvulsants [ 6 ], anti-inflammatories [ 7 ], and many others. There is increased interest in pyrroles and pyrrole derivatives exhibiting proven antioxidant effects [ 8 , 9 ]. Many heterocyclic hydrazones have shown antioxidant and neuroprotective activity, too [ 10 ].…”

“…Pharmaceuticals 2023, 16 and many others. There is increased interest in pyrroles and pyrrole derivatives exhibiting proven antioxidant effects [8,9]. Many heterocyclic hydrazones have shown antioxidant and neuroprotective activity, too [10].…”

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

“…On the other hand, a series of 2-alkyl-4-bromo-5-(trifluoromethyl)pyrrole-3-carbonitriles was obtained having excellent fungicidal activities against Alternaria solani and Fusarium oxysporum [ 8 ]. Substituted 3,4-dimethyl-1 H -pyrrole-2-carboxamides and carbohydrazide analogues could be considered potential antifungal and antimicrobial agents, especially against the pathogen Aspergillus niger [ 9 ].…”