ABSTRACT
Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.
Subject(s)
Diketopiperazines , Penicillium , Penicillium/chemistry , Diketopiperazines/pharmacology , Diketopiperazines/chemistry , Molecular Structure , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Drug Screening Assays, AntitumorABSTRACT
Deer velvet antlers, known as tonics, have created a large market as dietary supplements and have been consumed worldwide. Despite the high consumption of velvet antlers as dietary supplements, analytical methods for their identification and standardization remain limited. Quantitative analysis for gangliosides, considered quality indexes for velvet antlers, was developed to indirectly analyze the sialic acid obtained from chemical degradation. Owing to the complex and time-consuming chemical derivatization of gangliosides, a simple and rapid quality evaluation method for velvet antlers must be developed. For the first time, this study reports the isolation and structural elucidation of two new sphingomyelins (1 and 2), two known sphingomyelins (3 and 4), and four ceramides (5-8) as chemical markers from the velvet antlers of Cervus elaphus. To expedite and simplify the quality control of velvet antlers, advanced quantitative analysis of sphingolipids has been developed using ultra-performance liquid chromatography-mass spectroscopy.
ABSTRACT
A new dimeric alkaloid plakoramine A [(±)-1] was identified from a marine sponge Plakortis sp. Chiral-phase HPLC separation of (±)-1 led to the purified enantiomers (+)-1 and (-)-1 which both potently inhibited CBL-B E3 ubiquitin ligase activities. The absolute configurations of the enantiomers were determined by quantum chemical calculations. Scrutinization of the purification conditions revealed a previously undescribed, nonenzymatic route to form (±)-1 via photochemical conversion of its naturally occurring monomeric counterpart, plakinidine B (2).