Indole Diterpenoids from an Endophytic Penicillium sp

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Pharmacognosy

Background:

• Endophytes, such as Penicillium sp. isolated from Zingiber officinale roots, are a rich source of bioactive natural products.
• Indole diterpenoids represent a class of compounds with diverse biological activities, including cytotoxicity.
• The exploration of novel chemical scaffolds from natural sources is crucial for drug discovery.

Purpose of the Study:

• To isolate and characterize new indole diterpenoids from Penicillium sp. (strain ZO-R1-1) associated with Zingiber officinale.
• To evaluate the cytotoxic potential of the isolated compounds against various human cancer cell lines.
• To elucidate the structure and absolute configuration of novel compounds and investigate structure-activity relationships.

Main Methods:

• Chemical investigation using chromatographic techniques for isolation.
• Structure elucidation via 1D and 2D NMR spectroscopy and HRESIMS.
• Determination of absolute configuration using TDDFT-ECD calculations and single-crystal X-ray diffraction.
• Cytotoxicity assays using L5178Y, A2780, J82, and HEK-293 cell lines.

Main Results:

• Nine new indole diterpenoids (1-9) and 13 known congeners (10-22) were isolated.
• Compound 1 demonstrated significant cytotoxicity against L5178Y (IC50 = 3.6 μM) and A2780 (IC50 = 8.7 μM) cells.
• Compound 1 possesses a unique indole diterpenoid scaffold with a rare heterocyclic system, potentially contributing to its activity.

Conclusions:

• The endophyte Penicillium sp. from Zingiber officinale is a source of structurally novel indole diterpenoids.
• Compound 1 represents a new class of indole diterpenoids with promising cytotoxic activity against specific cancer cell lines.
• The unique scaffold of compound 1 warrants further investigation for its mechanism of action and therapeutic potential.