Secondary Metabolites from a Culture of the Fungus Neosartorya pseudofischeri and Their In Vitro Cytostatic Activity in Human Cancer Cells

Abstract

Four known (1, 2, 3, and 6) and three new compounds including a 1,4-diacetyl-2,5-dibenzylpiperazine derivative (4), a quinazolinone-containing indole derivative (5), and a new ester of 2,4-dihydroxy-6-methylbenzoic acid (7) were isolated from the fungus Neosartorya pseudofischeri S. W. Peterson. Compound 2 displayed in vitro growth inhibitory activity that ranged between the activities of etoposide and carboplatin, chosen as reference compounds, in six distinct cancer cell lines. Compound 1 displayed less activity than 2. Computer-assisted phase-contrast microscopy-related analysis revealed that 2 displayed cytostatic, not cytotoxic, effects in human U373 glioblastoma and A549 non-small cell lung cancer apoptosis-resistant cells with marked inhibition of mitotic rates. Cancer cells in the remaining phases of the cell cycle were unchanged. Flow cytometry analysis further confirmed that 2 does not induce apoptotic features in U373 or A549 cancer cells. Thus, 2 represents a novel chemical scaffold from which derivatives for anticancer cytostatic compounds can be derived.

Exploring the Chemodiversity and Biological Activities of the Secondary Metabolites from the Marine Fungus Neosartorya pseudofischeri

“…Compound 14 possessed a unique tetracyclic-fused skeleton, and it was the diastereomer of pseudofischerine [34]. We postulated that the biosynthetic pathway may involve d -valine, d -tryptophan and anthranilic acid as the precursors (Figure 5).…”

Fungi associated with rocks of the Atacama Desert: taxonomy, distribution, diversity, ecology and bioprospection for bioactive compounds

“…Among the bioactives compounds produced by Neosartorya species, neosartolactone and its 7‐methyl ester analogue that inhibited NO production in lipopolysaccharide‐activated murine macrophages (Yang et al ., ). From Neosartorya pseudofisheri , Eamvijarn and colleagues () reported the isolation of cadenene sesquiterpenes and the indole derivative eurochevalierine that displayed in vitro cytostatic activities against human cancer. The indole alkaloid sartorymensin, an analogue of tryptoquivaline and fiscalins produced by Neosartorya siamensis showed growth inhibition activity in human U373 and Hs683 glioblastoma, A549 non‐small cell lung cancer, MCF‐7 breast cancer and SKMEL‐28 melanoma cell lines (Buttachon et al ., ).…”

New Polyketides and New Benzoic Acid Derivatives from the Marine Sponge-Associated Fungus Neosartorya quadricincta KUFA 0081

“…Certain species are also found to produce interesting bioactive secondary metabolites that can be considered to have potential for drug development [ 1 ]. For this reason, we have investigated the bioactive secondary metabolites produced from the cultures of four Neosartorya species collected from soil in Thailand, i.e., Neosartorya glabra KUFC 6311 [ 2 ], N. pseudofischeri KUFC 6422 [ 3 ], N. siamensis KUFC 6349 [ 4 ] and N. fischeri KUFC 6344 [ 5 ], as well as six marine-derived species of Neosartorya , including N. paulistensis KUFC 7898 [ 6 ], N. laciniosa KUFC 7896 [ 5 ], N. spinosa KUFC 8104, N. tsunodae KUFC 9213 [ 5 ], N. siamensis KUFA 0017 and N. takakii KUFC 7898 [ 7 ], as well as one marine-derived Aspergillus species ( Aspergillus similanensis KUFA 0013) [ 8 , 9 ]. Recently, we have also reported the antifungal activity of the crude extract of N. quadricincta KUFA 0064, isolated from an agricultural soil in Southern Thailand, against plant pathogenic fungi, which are causative agents of diseases of economically-important plants of Thailand [ 10 ].…”