# Novel Cyclic Tetrapeptides as Neuraminidase Inhibitors from a Sponge-Associated Penicillium sp. SCSIO41035

## TL;DR

Scientists discovered new compounds from a sponge-associated fungus that show promising activity against neuraminidase, an enzyme linked to viral infections.

## Contribution

The study introduces three novel cyclic tetrapeptides with neuraminidase inhibitory activity from a marine-derived Penicillium species.

## Key findings

- Three new cyclic tetrapeptides (penicopeptides B−D) were isolated and structurally characterized.
- The compounds showed neuraminidase inhibition rates between 43.16% and 85.40% at 100 µg/mL.
- Asymmetric conformations in the tetrapeptides were attributed to the phenyl side chain of tyrosine residues.

## Abstract

Four new compounds and three new natural products (1−7), including three novel cyclic tetrapeptides (penicopeptides B−D), along with three known spiroquinazoline analogs (8–10), were isolated from rice medium cultures of a sponge-associated Penicillium sp. SCSIO41035. The structural elucidations, including the determination of absolute configurations, were accomplished by comprehensive analyses utilizing NMR spectroscopy, HRESIMS, optical rotation data, X-ray crystallography experiments and electronic circular dichroism calculations. Differential NMR signals between symmetric units in cyclotetrapeptides 1 and 2 arise from the asymmetric solution conformations as investigated through conformational searching and theoretical calculations. The asymmetric conformations were primarily caused by the flexibility of the tyrosine residue’s phenyl side chain, with its substantial electron density significantly influencing the NMR signals of nearby groups. Bioactivity screening results displayed that isolated compounds demonstrated good neuraminidase inhibitory activity, with inhibition rates ranging from 43.16% to 85.40% at a concentration of 100 µg/mL.