A Novel Lactam and Two Rare Mycophenolic Acid Derivatives from the Fungus Penicillium sclerotiorum JBHL321

Yue Wang; Xue-Ming Zhou; Jin-Feng Du; Xue-Feng Xu; Xin-Ming Song

doi:10.1002/cbdv.202401962

A Novel Lactam and Two Rare Mycophenolic Acid Derivatives from the Fungus Penicillium sclerotiorum JBHL321

Chem Biodivers. 2024 Oct 5:e202401962. doi: 10.1002/cbdv.202401962. Online ahead of print.

Authors

Yue Wang¹, Xue-Ming Zhou², Jin-Feng Du³, Xue-Feng Xu⁴, Xin-Ming Song⁵

Affiliations

¹ Hainan Normal University, college of chemistry and chemical engineerng, Guilin Yang campus, Hainan Normal University, 571127, Haikou, CHINA.
² Hainan Normal University, Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education Hainan Normal University, guilingyang, haikou, CHINA.
³ Hainan Vocational University of Science and Technology, Key Laboratory of Medicinal and Edible Plants Resources of Hainan Province, dongying, haikou, CHINA.
⁴ Hainan Vocational University of Science and Technology, Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education Hainan Normal University, dongying, haikou, CHINA.
⁵ Hainan Normal University, Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education Hainan Normal University, guilinyang, haikou, CHINA.

PMID: 39367690
DOI: 10.1002/cbdv.202401962

Abstract

A novel lactam penicillactam (1), two rare mycophenolic acid (MPA) derivatives penimycophens A and B (2 and 3), together with two known biogenetically related MPA derivatives (4 and 5) and a known alkaloid (6) were isolated from the Penicillium sclerotiorum JBHL321. The structures of these compounds were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD) calculations. Compound 1 represent the rare example of a oxygen bridge-linked lactam from natural products. Structurally, compounds 2 and 3 were rare MPA derivatives featuring a methoxy group at C-3. The inhibitory activity of compounds 1-6 against two phytopathogenic fungi, three phytopathogenic bacteria and four cancer cell lines were evaluated. Compounds 2-5 exhibited significant cytotoxic activity against HeLa, MCF-7, A549 and MGC-803 cells with IC50 values in the low micromolar to nanomolar. Compound 3 exhibited especially cytotoxic activity against four different cell lines with IC50 values ranging from 0.06 to 0.14 μM, compared to IC50 values ranging from 0.62 to 2.51 μM for epirubicin.

Keywords: Penicillium sclerotiorum JBHL321; antibacterial; cytotoxic activity; lactam; mycophenolic acid derivatives.