Nitidumpeptins A and B, Cyclohexapeptides Isolated from Zanthoxylum nitidum var. tomentosum: Structural Elucidation, Total Synthesis, and Antiproliferative Activity in Cancer Cells

Abstract

Nitidumpeptins A and B (1 and 2), two novel cyclic hexapeptides, were isolated from the herb Zanthoxylum nitidum var. tomentosum. Their planar structures were elucidated based on NMR and MS spectrometric analysis, and the absolute configurations were determined by the Marfey’s method. Structurally, 1 is a unique peptide with a backbone bearing a pyrrolidine-2,5-dione unit, which is the first occurrence moiety specifically in a naturally occurring cyclohexapeptide. The total synthesis of 1 and 2 was achieved by solution-phase in parallel with solid-phase peptide synthesis, and their absolute configurations were further confirmed. The combination of 2 with gefitinib exhibited synergistic antiproliferative activity in acquired gefitinib-resistant non-small cell lung cancer cells (HCC827-gef). The underlying mechanism for the antiproliferative activity of 2 was in part associated with the suppression of YAP expression in HCC827-gef cells.

Diisoprenyl Cyclohexene-Type Meroterpenoids with Cytotoxic Activity from a Mangrove Endophytic Fungus Aspergillus sp. GXNU-Y85

“…The detailed ECD instrument are described in the Supplementary Materials. The other measuring instruments used for the purification of the isolates and the materials used in the separation procedure were identical to our previous reports [9,10].…”

Four New Sesquiterpenoids from Zanthoxylum nitidum

“…In our previous work, phytochemical examination of Z. nitidum indicated the presence of alkaloids, amides, cyclic peptides, and lignanoids, which exhibit significant antiproliferative and anti‐inflammatory activities [1,8–10] . As part of a continuing research for natural antiproliferative agents from traditional folk herbs, the bioactive constituents from 95 % EtOH extract of Z. nitidum were explored, which resulted in the purification of 10 compounds ( 1 – 10 ), including four new sesquiterpenoids ( 1 – 4 ) as shown in Figure 1, and six known coumarins ( 5 – 10 ).…”

Synthesis and anti‐hepatocellular carcinoma activity in vitro of cyclic peptide GG‐8‐6 analogues

“…Natural products provide various chemical structures for the development of drug discovery. Among them, natural resource cyclic peptides belong to a particular class of compounds that display broad activities ranging from antiviral to antibacterial and anticancer applications [2–7]. Compared with linear peptides, cyclopeptides are more stable because of the absence of both free amino and carboxyl groups in their structures.…”