Combined in vitro and in silico approach to evaluate the inhibitory potential of an underutilized allium vegetable and its pharmacologically active compounds on multidrug resistant Candida species

Abstract

Candida infections and related mortality have become a challenge to global health. Nontoxic and natural bioactive compounds from plants are regarded as promising candidates to inhibit these multidrug resistant strains. In the present study, in vitro assays and in silico molecular docking approach was combined to evaluate the inhibitory effect of crude extracts from Allium ampeloprasum and its variety A. porrum on Candida pathogens. Phytochemical screening revealed the presence of phenolic acids and flavonoids in higher quantity. Spectral studies of the extracts support the presence of phenols, flavonoids and organosulfur compounds. Aqueous extract of A. ampeloprasum showed a total antioxidant capacity of 68 ± 1.7 mg AAE/ g and an IC 50 value of 0.88 ± 2.1 mg/ml was obtained for DPPH radicals scavenging assay. C. albicans were highly susceptible (19.9 ± 1.1 mm) when treated with aqueous A. ampeloprasum extract. Minimum inhibitory concentrations were within the range of 19–40 μg/ml and the results were significant (p ≤ 0.05). In silico molecular docking studies demonstrated that bioactive phytocompounds of A. ampeloprasum and A. porrum efficiently interacted with the active site of Secreted aspartyl proteinase 2 enzyme that is responsible for the virulence of pathogenic yeasts. Rosmarinic acid and Myricetin exhibited low binding energies and higher number of hydrogen bond interactions with the protein target. Thus the study concludes that A. ampeloprasum and A. porrum that remain as underutilized vegetables in the Allium genus are potential anti-candida agents and their pharmacologically active compounds must be considered as competent candidates for drug discovery.

Molecular docking: Bioactive compounds ofMimosa pudicaas an inhibitor ofCandida albicansSap 3

“…The distance produced by the presence of hydrogen bonds ranges from 2.11684 - 3.21115 Å, while the hydrophobic interaction has a distance of 4.60759 Å. Liberato et al 35 through an in vitro study, explained that gallic acid has potential as antifungal activity against Candida spp. Another study also reported, through in vitro and in silico studies by Uma Maheshwari Nallal et al 30 , that gallic acid, which is classified as an active phytochemical compound, is predicted to be an effective inhibitory agent of Sap from Candida species. Therefore, even though in this research gallic acid did not interact with the substrate binding site pocket or the catalytic residue of the target receptor, gallic acid was predicted to have a reasonably good interaction in inhibiting Sap 3.…”

“…The test ligands that have binding energy close to pepstatin are turgorin with a binding energy of 7,480 kcal/mol and K d 3289177.500 pM, then based on the binding energy respectively, D-glucuronic acid with a binding energy of 6.219 kcal/mol and Kd 27632016.000 pM, gallic acid with a binding energy of 6.053 kcal/mol and Kd 36567240.000 pM, L-norepinephrine with a binding energy of 5.770 kcal/mol and Kd 58956804.000 pM, mimosine with a binding energy of 5.599 kcal/mol and Kd 78682576.000 pM, L-ascorbic acid with a binding energy of 5.390 kcal/mol and Kd 111963792.000 pM, and the lowest binding energy is linolenic acid with a binding energy of 5.168 kcal/mol and Kd 162856752.000. The more positive value of the binding energy indicates stronger bond between the ligand and the target receptor whereas 29,30 . The results of the binding energies are presented in Figure 1.…”

“…The number of hydrogen bonds formed is known to determine binding strength in the receptor-ligand complexes. In addition, the efficiency of ligand binding to enzymes is also influenced by the binding energy 30 . The phytochemicals present in medicinal plants are known to have the potential as antimicrobial and various other biological activities 37 .…”

Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents

“…In addition, there is another hydrogen bond acceptor between the amino acid Lys89 and the carbonyl of the indolin-2-one ring. The role of hydrogen bonds in establishing out the ligand binding specificity [64,65], and its significance for biomacromolecules' properties and structures has been defined theoretically and experimentally [64]. The results indicated that the comparable positions and orientations within the investigated ligands assumed the binding site of the target enzyme.…”

Gene expression, molecular docking, and molecular dynamics studies to identify potential antifungal compounds targeting virulence proteins/genes VelB and THR as possible drug targets against Curvularia lunata

“…Azoles (itraconazole and voriconazole) and polyenes (amphotericin B) are antifungals that have widely been used to control invasive human fungal infections for more than 4 decades ( Jørgensen and Heick, 2021 ; Uma Maheshwari Nallal et al, 2021 ). The clinical use of azoles is of high priority since there are only a few available alternatives for prophylactic and therapeutic treatment of C. lunata infections ( Chowdhary et al, 2014 ; Chang et al, 2019 ).…”