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two p-terphenyl derivatives and one 4,5-diphenyl-2-pyrone
analogue, peniterphenyls A–C (1–3), together with five known p-terphenyl derivatives
(4–8) and sulochrin (9), were obtained from a deep-sea-derived Penicillium sp. SCSIO41030. Their structures were elucidated using extensive
NMR spectroscopic and HRESIMS data and by comparing the information
with literature data. Peniterphenyl B (2) represented
the first reported natural product possessing a 4,5-diphenyl-substituted
2-pyrone derivative. The p-terphenyl derivatives
displayed inhibitory activities against HSV-1/2 with EC50 values ranging from 1.4 ± 0.6 to 9.3 ± 3.7 μM in
Vero cells, which showed that they possessed antiviral activities
with low cytotoxicity, superior to the current clinical drug acyclovir
(EC50 3.6 ± 0.7 μM). Peniterphenyl A (1) inhibited HSV-1/2 virus entry into cells and may block
HSV-1/2 infection through direct interaction with virus envelope glycoprotein
D to interfere with virus adsorption and membrane fusion, and thus
differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A (1) could be a promising lead compound against HSV-1/2.