Rare Glutamic Acid Methyl Ester Peptaibols from Sepedonium ampullosporum Damon KSH 534 Exhibit Promising Antifungal and Anticancer Activity

Fungal species of genus Sepedonium are rich sources of diverse secondary metabolites (e.g., alkaloids, peptaibols), which exhibit variable biological activities. Herein, two new peptaibols, named ampullosporin F (1) and ampullosporin G (2), together with five known compounds, ampullosporin A (3), peptaibolin (4), chrysosporide (5), c(Trp-Ser) (6) and c(Trp-Ala) (7), have been isolated from the culture of Sepedonium ampullosporum Damon strain KSH534. The structures of 1 and 2 were elucidated based on ESI-HRMSn experiments and intense 1D and 2D NMR analyses. The sequence of ampullosporin F (1) was determined to be Ac-Trp1-Ala2-Aib3-Aib4-Leu5-Aib6-Gln7-Aib8-Aib9-Aib10-GluOMe11-Leu12-Aib13-Gln14-Leuol15, while ampullosporin G (2) differs from 1 by exchanging the position of Gln7 with GluOMe11. Furthermore, the total synthesis of 1 and 2 was carried out on solid-phase to confirm the absolute configuration of all chiral amino acids as L. In addition, ampullosporin F (1) and G (2) showed significant antifungal activity against B. cinerea and P. infestans, but were inactive against S. tritici. Cell viability assays using human prostate (PC-3) and colorectal (HT-29) cancer cells confirmed potent anticancer activities of 1 and 2. Furthermore, a molecular docking study was performed in silico as an attempt to explain the structure-activity correlation of the characteristic ampullosporins (1–3).

Anti-Cancer Activity of Gabapentin and Chiral Amino Acids-Based Hybrid-Peptides against MCF-7 Breast Cancer Cell-Line

Aims: Herein, we report the cytotoxicity of gabapentin-based peptides (11a-11j) using L-alanine and L-phenyl alanine chiral amino acids for peptide bond formation in ten efficient and straightforward steps. The in vitro MTT assays of derived molecules on the MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to the control (100% cell proliferation). Methods: The ten steps synthetic methods were adapted for the synthesis of the Gabapentin-based peptide derivatives through BOC- deBOC methods and using EDC-HCl, DMAP and commercially available solvents. All the synthesized peptides were unambiguously characterized with the help of spectroscopic (IR, 1H NMR, 13C-NMR, mass spectra, and elemental) data analysis. Results: The Compounds 11a, 11b, 11h,11i, and 11j showed a remarkable antiproliferative (cell death) activity, with % cell proliferation values ranging from 25-38 %. Conclusion: The study showed that the compounds with some specific functionalities like, benzylic and trifluoromethyl functionality enhanced the potency with comparable %cell proliferation and cell death. Based on the findings in this work and their easily accessible molecular structures, compounds 11a and 11j are worthy of further biological investigations.

Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)

d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino acid enantiomers in cells and tissues. Various quantification methods have been developed for measurements of chiral amino acids. However, each method has advantages and disadvantages. Additionally, measuring the amino acid enantiomers in crude biological samples requires a higher selectivity. In this study, we developed a quantification method for amino acid enantiomers using derivatization with Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA) followed by liquid chromatography–tandem mass spectrometry (LC/MS/MS) with a conventional reversed-phase column. We simultaneously identified 10 chiral amino acids. Furthermore, we applied this method to investigate murine tissue samples and examined the effect of aging on the amino acid levels in aged brain regions. We found that aging decreased the levels of both d-serine and d-aspartate in the hippocampus. In addition, d-Phenylalanine in the thalamus significantly increased with age. In conclusion, our method is suitable for the quantification of the d-amino acids in crude biological samples and may contribute to elucidating the biological roles of chiral amino acids.

Amino acid-derived bisphenolate palladium complexes as C-C coupling catalysts

A series of amine bisphenol (ABP) pro-ligands featuring amino acid ester pendant arms were prepared. Optimisation of the synthetic method allowed the facile incorporation of naturally occurring, chiral amino acids...