Discovery of a Secalonic Acid Derivative fromAspergillus aculeatus, an Endophyte ofRosa damascenaMill., Triggers Apoptosis in MDA-MB-231 Triple Negative Breast Cancer Cells

Abstract

A new secalonic acid derivative, F-7 ( 1 ), was isolated from the endophytic Aspergillus aculeatus MBT 102, associated with Rosa damascena . The planar structure of 1 was established on the basis of 1D and 2D NMR and ESI-TOF-MS spectra. The relative configuration of 1 was determined applying a combined quantum mechanical/NMR approach and, afterward, the comparison of calculated and experimental electronic circular dichroism spectra determined the assignment of its absolute configuration. The compound possesses strong cytotoxic activity against triple negative breast cancer (TNBC) cells. It was found to induce apoptosis, as evidenced by scanning electron microscopy and phase contrast microscopy. Furthermore, flow cytometry analyses demonstrated that 1 induced mitochondrial damage and reactive oxygen species mediated apoptosis, arresting the G1 phase of the cells in a dose-dependent manner. Also, the compound causes significant microtubule disruption in TNBC cells. Subsequently, 1 restricted the cell migration leading to the concomitant increase in expression of cleaved caspase and PARP.

Bioactive Indole Diketopiperazine Alkaloids from the Marine Endophytic Fungus Aspergillus sp. YJ191021

“…13 C (150 MHz) NMR Data of 1-6. three oxygen-bearing carbons), four olefinic methines, and six sp 2 nonprotonated carbons. The 1 H and 13 C NMR data of 6 resembled those of gartryprostatin B[15], with the exception that C-17 oxygen-bearing sp3 -methine signal (δ C 93.6) and C-16 sp 3 -methylene signal (δ H 2.10, 2.33; δ C 31.6) had a clear difference. With six degrees of unsaturation accounting for the eight aromatic carbons and two carbonyls, there must be a heptatomic ring system to meet the 13 degrees of unsaturation in 6.…”

“…In this study, we described the isolation and structure identification of six new prenylated indole diketopiperazine alkaloids (1)(2)(3)(4)(5)(6), together with eight known analogues: Gartryprostatin A (7) [15], gartryprostatin B (8) [15], sclerotiamide (9) [16], notoamide H (10) [17], 6-epi-notoamide R (11) [18], notoamide R (12) [19], (-)-notoamide I (13) [20], and gartryprostatin C (14) [15] (Figure 1) from the marine-derived endophytic fungus Aspergillus sp. YJ191021.…”

“…Endophytic fungi are prolific microbial resources for the production ability of many biologically active secondary metabolites, which can help the host to resist pathogenic microorganisms [ 2 ]. Various endophytic fungi have drawn substantial attention due to their potential to produce chemically diverse and biologically active secondary metabolites with anti-cancer, anti-microbial, anti-viral, and insecticidal activities [ 3 , 4 , 5 , 6 ]. In our continuous searching for novel bioactive secondary metabolites from marine endophytic fungi [ 7 , 8 , 9 ], the Aspergillus sp.…”

The Natural Products and Extracts: Anti‐Triple‐Negative Breast Cancer in Vitro

“…Besides, it also induced G1 phase arrest in MDA-MB-231 cells during cell cycle progression. [54] The inosine 5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme in the de novo synthesis of guanine nucleotides was always overexpressed in TNBC, which is regarded as a potential target for cancer therapy. Shikonin (24) (Figure 8), the bioactive component of Lithospermum erythrorhizon was a novel competitive inhibitor of IMPDH2.…”

Antiangiogenic properties of lichen secondary metabolites

“…The secalonic acid family, natural mycotoxins, including dimers of six different monoxanthones (secalonic acids A-F) with a dimeric tetrahydroxanthenone skeleton exhibits a wide range of anticancer activities (Farooq et al, 2020).…”