A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

Al‐Masoudi, Najim A.; Mahdi, Kuthiar M.; Abdul-Rida, Nabeel A.; Saeed, Bahjat A.; Engel, Matthias

doi:10.1016/j.steroids.2015.05.002

Cited by 6 publications

(1 citation statement)

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“…Our in silico finding corroborate these observations. Al‐Masoudi et al () showed the in silico inhibition of CYP17A1 by some newly synthesized pregnenolone analogs which interacted with CYP17A1 through two hydrogen bonds at Arg239 and Gly297 position and hydrophobic interaction at Tyr201. These interactions show similarity to H‐bonds of DEHP with CYP17A1 at Ile 443 and Gly 444 in the present study.…”

Section: Discussionmentioning

confidence: 99%

Molecular docking reveals the potential of phthalate esters to inhibit the enzymes of the glucocorticoid biosynthesis pathway

et al. 2016

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Glucocorticoids (GCs) are well known to exert broad-based effects on metabolism, behavior and immunity. Their impaired synthesis and production lead to adverse health effects. Some environmental toxicants, including phthalate esters (PAEs), are associated with endocrine disruption. These endocrine-disrupting chemicals (EDCs) also cause adrenal toxicity and alteration of GC biosynthesis and their functions. Using in silico tools of Schrodinger Maestro 9.4, we performed a molecular docking study of 32 ligands including PAEs of a known endocrine-disrupting potential with the selected enzymes of the GC biosynthesis pathway (GBP) such as CYP11A1, CYP11B2, CYP19A1, CYP17A1, CYP21A2 and 3α/20β-HSD. Binding affinities of the PAEs were compared with known inhibitors of these enzymes. Amongst PAEs, diphenyl benzene-1, 2 - dicarboxylate (DPhP) showed the lowest docking score of -8.95616 kcal mol against CYP21A1. Besides, benzyl butyl benzene-1,2-dicarboxylate (BBzP), bis(7-methylnonyl) benzene-1,2 dicarboxylate (DIDP) and bis(2-ethylhexyl) benzene-1,2-dicarboxylate (DEHP) also showed comparable molecular interaction with enzymes of GBP. DPhP showed a significant molecular interaction with different enzymes of GBP such as CYP21A1, CYP11A1 and CYP11B2. These interactions mainly included H-bonding, hydrophobic, polar and van dar Waals' interactions. Interestingly, this in silico study revealed that certain PAEs have more inhibitory potential against enzymes of GBP than their respective known inhibitors. Such studies become more relevant in the risk assessment of exposure to mixtures of phthalate eaters. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%