Three previously undescribed steroidal glycoalkaloids from Solanum lyratum and their anti-tumor activities

In the present study,three previously undescribed steroidal glycoalkaloids(compounds 1–3)were isolated from Solanum lyratum.Their structures were elucidated based on comprehensive spectroscopic data.Their anti-angiogenesis and anti-metastatic activities were evaluated by MTT and wound-healing assays,respectively.Tumor-derived vascular endothelial cells(TdECs),obtained by co-culture of A549 and human umbilical vein endothelial cells(HUVECs),were treated with compounds 1–3.Results showed that compounds 1–3 significantly inhibited the migration of TdECs at 25μM despite the weak cytotoxic activities,which indicated that the compounds exerted anti-tumor activities by inhibiting metastasis,rather than directly inhibiting the proliferation of TdECs.

Steroidal scaffold decorations in Solanum alkaloid biosynthesis

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as tomato,potato,and eggplant.Although it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic activities.Among these,α-solasonine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory activities.Notably,α-solasonine andα-solamargine,along with the core steroidal aglycone solasodine,are the most widespread SGAs produced among the Solanum plants.However,it is still unknown how plants synthesize these bioactive steroidal molecules.Through comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from S.nigrum that converts the starting cholesterol precursorto solasodine aglycone,and the downstreamα-solasonine,α-solamargine,and malonyl-solamargine SGA products.We further identified six enzymes from cultivated eggplant that catalyze the production ofα-solasonine,α-solamargine,and malonyl-solamargine SGAs from solasodine aglycone via glycosylation and atypical malonylation decorations.Our work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

Two new glycoalkaloids from Solanum lyratum Thunb.

To study the alkaloids of Solanum lyratum Thunb.ODS and silica gel column chromatography combined with HPLC were used to separate and purify the alkaloids.Seven alkaloids were identified via UHPLC-ESI-Q-TOF-MS,1 D and 2 D NMR,respectively 15β-ethoxy-(3β,5α,25 R)-16,23-epoxy-23,24-imino-cholestan-16,20,23(N)-triene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyran-oside(1),15β-hydroxyl-(3β,25 R)-16,23-epoxy-23,24-imino-cholestan-5,16,20,23(N)-tetraene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactop-yranoside(2),Solalyraine A(3),Solalyraine B(4),16,23-epoxy-22,26-imino-cholest-22(N),23,25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside(5),N-(4-amino-butyl)-3-(3-hydroxy-4-methoxy-phenyl)-E-acrylamide(6)and magnoflorine(7).Among them,compounds 1 and 2 were two new steroidal glycoalkaloids that has not been reported in the literature,and compound 7 was isolated from S.lyratum for the first time.