Molecular docking-based screening of newly designed coumarin derivatives with potential antifungal activity against lanosterol 14 α-demethylase

Villaseñor-Granados, Tayde Osvaldo; García, Santiago Álvarez; Vázquez, Miguel Á.; Robles, Juvencio

doi:10.1007/s00214-016-1965-y

Cited by 10 publications

(10 citation statements)

References 27 publications

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“…Compound 1a, with a binding affinity of -7.11 kcal/mol.atom towards the MTCYP51 active site, most closely approached the LE of -7.3 kcal/mol.atom previously described for fluconazole. 33 Compounds 1b and 1d also exhibit good affinity towards the MTCYP51 active site, as can be inferred from their LE values. A subtle but very important difference was observed for the binding mode of 1c compared to the other three set 1 molecules.…”

Section: Dockingmentioning

confidence: 73%

“…2). [33] The analysis of the structure of fluconazole (left) and of a generalized version of the present coumarins reveals similarities (Fig. 3).…”

Section: Chemistrymentioning

confidence: 86%

“…Applying a previously reported methodology, [33] docking simulations were carried out to compare the binding modes of the test and reference compounds. By analyzing the five most probable cavities in the MTCYP51 target, the largest was found to be the active site.…”

Section: Dockingmentioning

confidence: 99%

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Synthesis, biological evaluation and docking study of possible antifungal compounds with a coumarin-containing triazole side chain

et al. 2019

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Abstract. Due to increasing drug resistance by Candida species, especially in hospitals, the search for new antifungal agents has intensified. The incorporation of the coumarin scaffold into several nitrogen-containing heterocyclic moieties reportedly increases antimicrobial efficiency. The aim of this study was to design and synthesize a series of simple coumarin-linked triazole derivatives and test their possible antifungal activity against four Candida species. Docking simulations were conducted to explore the binding properties of the test compounds and compare them to reported data on fluconazole, the reference drug. Starting from 3-acetylcoumarins, coumarins 2a-d, 3a-c and 4a-d were obtained in high yields. The concentration of each compound needed to inhibit the Candida species was determined by serial dilution. An inhibition of 62% of C. albicans was produced by 2b (300 µg/ml), 87% of C. tropicalis by 3a (100 µg/ml), 89% of C. parapsilosis by 3a (500 µg/ml), and 87% of C. glabrata by 4a (300 µg/ml). The values of antifungal activity were similar for the coumarin derivatives and fluconazole, the latter of which induced 90% inhibition of the four yeasts at 500 µg/ml. According to the docking simulations, the interactions at the active site of the lanosterol 1,4-demethylase enzyme (CYP51) are similar for the test compounds and fluconazole. The subcellular location of the derivatives was identified as the mitochondrion. These coumarins are characterized by structural simplicity, with the simplest structures showing better antifungal activity than fluconazole. Further research is needed to isolate CYP51 and directly test its inhibition by coumarin derivatives. Resumen. Una serie de moléculas de cumarina-triazol se sintetizaron y evaluaron contra diferentes especies de Candida. Las cumarinas 2a-d, 3a-c y 4a-d se obtuvieron utilizando como material de partida las 3-acetilcumarinas en altos rendimientos. La concentración necesaria de las moléculas para mostrar actividad antifúngica contra las cuatro especies de Candida se determinó mediante un método de diluciones seriadas. Se reporta un 62% de inhibición de C. albicans usando 2b (300 µg/ml), 87% de inhibición contra C. parapsilosis por 3a (500 µg/ml), y un 87% de inhibición a C. glabrata por 4a (300 µg/ml). El efecto de las cumarinas es comparado con el fármaco de referencia fluconazol, que induce un 90% de inhibición en todas las cepas usando 500 µg/ml. Los resultados del estudio Docking muestran que las interacciones de todas las moléculas en el sitio activo de la enzima CYP51 son similares a las interacciones presentadas por el fluconazol. Finalmente, tomando ventaja de las propiedades fluorescentes de las cumarinas, la localización subcelular y penetración de los compuestos, fue localizada en las mitocondrias. Las cumarinas reportadas, además de presentar sencillez estructural, también presentan valores de inhibición de las cepas comparables, y en los casos mencionados, mejores que el fármaco de referencia.

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Section: Dockingmentioning

confidence: 73%

“…2). [33] The analysis of the structure of fluconazole (left) and of a generalized version of the present coumarins reveals similarities (Fig. 3).…”

Section: Chemistrymentioning

confidence: 86%

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Synthesis, biological evaluation and docking study of possible antifungal compounds with a coumarin-containing triazole side chain

et al. 2019

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“…These compounds could be binding to the active site of the enzyme, DNA gyrase which is responsible for the bacterial replication and thus inhibiting the bacterial growth . In the case of antifungal activity, these compounds might be inhibiting Lanosterol 14 α‐demethylase enzyme which is responsible for biosynthesis of Ergosterolan essential component of fungal cell membrane …”

Section: Resultsmentioning

confidence: 99%

“…[25] In the case of antifungal activity, these compounds might be inhibiting Lanosterol 14 α-demethylase enzyme which is responsible for biosynthesis of Ergosterolan essential component of fungal cell membrane. [26] 3 | EXPERIMENTAL…”

Section: Antimicrobial Activitymentioning

confidence: 99%

One‐pot multi‐component synthesis of novel ethyl‐2‐(3‐((2‐(4‐(4‐aryl)thiazol‐2‐yl)hydrazono)methyl)‐4‐hydroxy/isobutoxyphenyl)‐4‐methylthiazole‐5‐carboxylate derivatives and evaluation of their in vitro antimicrobial activity

Deshineni

Velpula

Koppu

et al. 2019

Journal of Heterocyclic Chem

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A novel series of ethyl‐2‐(3‐((2‐(4‐(4‐aryl)thiazol‐2‐yl)hydrazono)methyl)‐4‐hydroxy/isobutoxyphenyl)‐4‐methylthiazole‐5‐carboxylate derivatives (4a‐f and 5a‐f) were synthesized by employing one‐pot multi‐component approach involving ethyl 2‐(3‐formyl‐4‐oxy/isobutoxyphenyl)‐4‐methylthiazole‐5‐carboxylate, thiosemicarbazide and various phenacyl bromides/3‐(2‐bromoacetyl)‐2H‐chromen‐2‐one/2‐(2‐bromoacetyl)‐3H‐benzo[f]chromen‐3‐onein ethanol in the presence of catalytic amount of acetic acid. The structures of all the synthesized compounds were confirmed with spectral analysis, ie, IR, 1H NMR, 13C NMR and mass spectrometry, and all the compounds were screened for their in vitro antimicrobial activity.

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Structural activity, fungicidal activity and molecular dynamics simulation of certain triphenyl methyl imidazole derivatives by experimental and computational spectroscopic techniques

Mol

Aruldhas

Joe³

et al. 2019

Spectrochimica Acta Part A: Molecular and Biomolecular Spectros

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Molecular docking-based screening of newly designed coumarin derivatives with potential antifungal activity against lanosterol 14 α-demethylase

Cited by 10 publications

References 27 publications

Synthesis, biological evaluation and docking study of possible antifungal compounds with a coumarin-containing triazole side chain

Synthesis, biological evaluation and docking study of possible antifungal compounds with a coumarin-containing triazole side chain

One‐pot multi‐component synthesis of novel ethyl‐2‐(3‐((2‐(4‐(4‐aryl)thiazol‐2‐yl)hydrazono)methyl)‐4‐hydroxy/isobutoxyphenyl)‐4‐methylthiazole‐5‐carboxylate derivatives and evaluation of their in vitro antimicrobial activity

Structural activity, fungicidal activity and molecular dynamics simulation of certain triphenyl methyl imidazole derivatives by experimental and computational spectroscopic techniques

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