Penaloidines A and B: two unprecedented pyridine alkaloids from Penicillium sp. KYJ-6

Abstract

Penaloidines A (1) and B (2), a pair of epimers and unprecedented pyridine alkaloids possessing a tetrahydrofuro[3,2-c][2,7]naphthyridinyl scaffold, were characterized from Penicillium sp. KYJ-6. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses, electronic circular dichroism (ECD) calculations and X-ray diffraction. A plausible biosynthetic pathway for 1–2 was proposed. Compounds 1 and 2 exhibited acetylcholinesterase inhibitory activity with IC₅₀ values of 14.85 ± 0.41 and 41.27 ± 0.56, respectively. The interactions of 1 and 2 with the AChE enzyme were explored by employing molecular docking studies to provide insights into the mechanism of their AChE inhibitory activity.