Lepithiohydimerins A—D: Four Pairs of Neuroprotective Thiohydantoin Dimers Bearing a Disulfide Bond from Maca (Lepidium meyenii Walp.)

Abstract

Main observation and conclusion An HPLC‐UV‐guided separation was performed and four pairs of unprecedented macathiohydantoin dimers, lepithiohydimerins A—D (1—4) bearing a rare disulfide bond were isolated from the tubers of Maca. Their structures were unambiguously confirmed by NMR spectroscopic, X‐ray crystallographic and electronic circular dichroism (ECD) analyses. At the concentration of 20 μmol/L, compounds 2‐1, 2‐2, and 4‐1 increased the viability of PC12 cells with the cell viability at (72.06 ± 1.14)%, (72.64 ± 1.49)%, and (70.93 ± 1.22)%, respectively. Furthermore, the serial concentration experiment showed that they can protect PC12 cells in a dose‐dependent manner.

Spiroleiferthione A and Oleiferthione A: Two Unusual Isothiocyanate-Derived Thioketone Alkaloids from Moringa oleifera Lam. Seeds

“…The 1 H NMR spectrum of 1 has peaks indicating an aromatic ring AA′BB′ system [ δ H 7.04 (2H, d, J = 8.4 Hz, H-2′, 6′) and δ H 6.62 (2H, d, J = 8.4 Hz, H-3′, 5′)], one nitrogen-bearing methylene [ δ H 4.72 ( 1 H, d, J = 15.0 Hz, H-7′a) and 4.61( 1 H, d, J = 15.0 Hz, H-1′b)], one saturated methylene [ δ H 2.41 ( 1 H, dd, J = 6.0, 13.2 Hz, H-9a) and 1.95 ( 1 H, dd, J = 7.2, 13.2 Hz, H-9b)], two nonequivalent methines [ δ H 3.85 ( 1 H, dq, J = 6.0, 6.0 Hz, H-7) and 3.83 ( 1 H, ddd, J = 7.2, 6.0, 6.0 Hz, H-8)], and one methyl [ δ H 1.09 (3H, d, J = 6.0 Hz, H 3 -10)]. The 13 C NMR and DEPT spectra display signals corresponding to the above proton-bearing units include two additional quaternary carbonyls assigned as carboxylic ( δ C 172.9, C-4), and thiourea carbonyl ( δ C 182.6, C-2) groups [ 3 , 8 , 9 ], and three quaternary carbon resonances that were assigned as two aromatic carbons, including an oxygen-bearing carbon ( δ C 126.9 and 157.3, respectively) and one nitrogen/oxygen-bearing carbon ( δ C 90.7) ( Table 1 ). These spectroscopic data, and those of the reported thiohydantoin derivatives (Lee et al, 2019; Peng et al, 2021; Yu et al, 2017) indicate that 1 is a thiohydantoin derivative, as confirmed by 2D NMR data analysis ( Figure 2 ).…”

“…To date, no more than 50 naturally occurring thiohydantoin derivatives have been reported in the literature [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Spiroleiferthione A is a rare 2-thiohydantoin with an unprecedented heterocyclic spiro skeleton that differs from these reported thiohydantoin derivatives.…”

“…However, on account of the limitations, the diabetic-nephropathy-protective activity of Compound 1 in vivo and its mechanism of action were not further investigated. Although it has been reported that natural imidazole-2-thione derivatives possess biological activities, such as antioxidant, hepatoprotective, and epithelial–mesenchymal transition inhibition properties [ 12 , 13 , 14 ], and natural 2-thiohydantoin derivatives showed anti-neuroinflammatory [ 3 , 4 , 8 ], antibacterial [ 9 ], anticancer [ 8 , 26 ], hypolipidemic [ 2 ], anticarcinogenic [ 2 ], antimutagenic [ 2 ], and antithyroidal [ 2 ] activities, a wider range of biological effects was not further evaluated due to the limitations of the two compounds. Although various bioactivities of 2-thiohydantoin derivatives have been reported, the antidiabetic nephropathy activity was investigated in this study for the first time.…”

“…Thiohydantoins, imidazole-2-thione derivatives, and isosteric analogues of hydantoin exhibit numerous biological activities, such as anticancer, anti-inflammatory, immunoregulatory, and antimicrobial properties [ 1 ]. To date, no more than 50 naturally occurring thiohydantoin derivatives have been reported in the literature [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. They have mainly been discovered in plants of the Brassicaceae (syn.…”

“…Cruciferae) family, such as Lepidium meyenii Walp., Armoracia rusticana P.G. Gaertn, and Pugionium cornutum (L.) Gaertn [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Only two imidazole-2-thione derivatives derived from ergothioneine have been isolated from a plant extract, although all previously reported ergothioneine-derived natural products are from fungal and animal sources [ 11 ].…”