Discovery of Natural Dimeric Naphthopyrones as Potential Cytotoxic Agents through ROS-Mediated Apoptotic Pathway

Abstract

A study on the secondary metabolites of Aspergillus sp. XNM-4, which was derived from marine algae Leathesia nana (Chordariaceae), led to the identification of one previously undescribed (1) and seventeen known compounds (2−18). Their planar structures were established by extensive spectroscopic analyses, while the stereochemical assignments were defined by electronic circular dichroism (ECD) calculations. The biological activities of the compounds were assessed on five human cancer cell lines (PANC-1, A549, MDA-MB-231, Caco-2, and SK-OV-3), and one human normal cell line (HL-7702) using an MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide] assay. Among them, the dimeric naphthopyrones 7, 10 and 12 exhibited potent cytotoxicity. Further mechanism studies showed that 12 induced apoptosis, arrested the cell cycle at the G0/G1 phase in the PANC-1 cells, caused morphological changes and generated ROS; and it induces PANC-1 cells apoptosis via ROS-mediated PI3K/Akt signaling pathway.

Acetylcholine esterase inhibitory activity of green synthesized nanosilver by naphthopyrones isolated from marine-derived Aspergillus niger

“…is generous producer of naphthopyrone phenolic compounds under certain stress conditions [39]. These compounds exhibited diverse biological properties as anti-bacterial [40,41], hepatoprotective [42], Acyl CoA inhibitor [43], cytotoxic [44], anti-mutagenic [45], antiallergic [46], antiviral [47], non-toxic antioxidant [48], anti-xanthine oxidase [49], anti-tyrosinase [47], anti-HIV-1 integrase [47], anti-COX-2 [50] and anti-AChE/anti-β-secretase [51] activities. Considering AD as a multifactorial disease, the inhibition of the latter enzyme may be potentiated by reducing oxidative stress secured by the inherent potent antioxidant activity, thus rendering naphtha-γ-pyrones worthy candidates for alleviating AD symptoms.…”

Online extraction and enrichment coupling with high‐speed counter‐current chromatography for effective and target isolation of antitumor anthraquinones from seeds of Cassia obtusifolia

“…Natural anthraquinones and naphthopyrones have been reported to exhibit potent antitumor activities on a variety of tumor cell lines [25,26]. Glycosides, to some extent, present weaker antitumor activities than aglycones probably because of the sterically inhibited binding with enzymes or receptors [27].…”

Assignment of Absolute Configurations of Two Promising Anti-Helicobacter pylori Agents from the Marine Sponge-Derived Fungus Aspergillus niger L14

“…On basis of their similar 1 H and 13 C NMR spectra [ 18 ] ( Supplementary Figures S3–S6 ), their molecular formulas are deduced as C 32 H 26 O 10 . By further careful comparison of their 1 H and 13 C NMR spectral data with the literature ( Table 1 ), compounds 1 and 2 were identified as fonsecinone A [ 14 ] and isoaurasperone A [ 19 ], respectively, which are dimeric naphtho- γ -pyrone analogs.…”