In silico analysis of nitrones with possible Nrf2 agonist activities

Abstract

Triggering of Nrf2 signaling results in improvedadipogenesis and insulin sensitivity in diet-induced obesitymouse models. Sulforafane (SFN, a Nrf2 agonist). Thenitrone compound DMPO has recently been shown toincrease the expression of several genes under the controlof Nrf2. Herein we used in silico tools for analyzing thestructural similarities between DMPO, a series of nitronecompounds, and SFN. The structures of 14 molecules areto be compared. A correlative number from 1 to 14 wasassigned to each compound for identification. Numbers 1and 2 were intended for the two "pattern" compounds, 1 forSFN, a known Nrf2 agonist, and 2 for DMPO. Using thePaDEL program, 1444 molecular descriptors (DMs) werecalculated, which include 1D and 2D characteristics of thetopological structure. The formation of 3 and 4 clusters wasuseful to see that compounds 6, 7, 8, and 9 are always inthe same cluster forming a very homogeneous group andthat compounds 1, 2, and 14 also present high structuralsimilarities. In a dendrogram graph, 2 clusters can berecognized. In cluster 1, the greatest similarities are foundbetween compounds 6 and 8, a little less with 9 and 7would present less structural similarity although it remainsin the same cluster, as indicated by the silhouetteplots. The second cluster shows a similarity betweencompounds 3, and 4, and to a lesser extent with 5 and 10,11 and 13 would form a sub-group. The pattern compounds1 and 2 form a group somewhat separated from the restwith compound 14, which is the one that would have thegreatest similarity with 1 (sulforaphane). In silico analysiscomparing structural similarities between compounds isallowing saving time and resources for furthercorroboration of their activity to induce Nrf2 signaling invitro and in vivo.