Chaetolactam A, an Azaphilone Derivative from the Endophytic Fungus Chaetomium sp. g1

Abstract

Chaetolactam A (1), an unprecedented azaphilone derivative bearing a unique 9-oxa-7-azabicyclo[4.2.1]octan-8onering system, together with two new compounds, 11-epi-chaetomugilide B (2) and chaetomugilide D (3) was isolated from an endophytic fungus, Chaetomium sp. g1. Notably, extensive NMR data analyses, NMR calculations with DP4 and DP4+ analyses, ECD calculations, and the RDC method were employed to establish the structure of 1. Furthermore, 2 exhibited potent apoptosis induction activity by mediating caspase-3 activation and PARP degradation at 3 μM in HL-60.

Recent Findings in Azaphilone Pigments

“…A screening by LC-MS/MS-GNPS data base of a strain of an endophytic plant fungus Chaetomium sp. g1 resulted in the isolation of chaetolactam A (38), a unique 9-oxa-7-azabicyclo[4.2.1]octan-8-onering system with two new compounds chaetoviridins derivatives, 11-epi-chaetomugilide B (39), and chaetomugilide D (40) [44]. Another plant endophytic fungus C. globosum isolated from the desert Asteraceae species, Artemisia desterorum, yielded globosumone (41), a new stereoisomer of the known chaetoviridin E [45].…”

“…Four unprecedented bisazaphilones hybridorubrins A-D (42)(43)(44)(45) were isolated together with two new mitorubrin-type azaphilones, fragirubrins F-G (46-47) [46] from Hypoxylon fragiforme. The main differences among them are the acyl substituents in the lenormandin/fragirubrin-type moiety.…”

“…The azaphilones ( 39 ) and ( 40 ) showed moderate activity against leukemia HL-60 and human breast cancer. However, ( 39 ) exhibited potent apoptosis induction activity by mediating caspase-3 activation and PARP degradation at 3 μM in leukemic cells HL-60 [ 44 ]. Another interesting result was the potent cytotoxic activity showed by the dimeric azaphilones ( 89 ) and ( 90 ) against five different human cell lines.…”

“… Chemical structures of Chaetomium azaphilones: 25 : Chaephilone C (1R,7S,8R,8aR,9E,11S,4′R,5′R); 26 : chaephilone D; 27 : chaephilone C*; 28 : cochliodone J; 29 : N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A; 30 : 4′-epi-N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A; 31 : N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin A, 32 : 4′-epi-N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin A; 33 : N-(3,7-Dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin E; 34 : N-(3-Methyl-2-butenyl)-2-aza-2-deoxychaetoviridin E; 35: 4′,5′-dinor-5′-Deoxy-N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2- deoxychaetoviridin A; 36 : 4′,5′-dinor-5′-Deoxy-N-(3-methyl-2-butenyl)-2-aza-2-deoxy- chaetoviridin A; 37 : seco-chaetomugilin; 38 : chaetolactam A; 39 : 11-epi-chaetomugilide B; 40 : chaetomugilide D; 41 : globusumone [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. …”

Chaetomugilins and Chaetoviridins—Promising Natural Metabolites: Structures, Separation, Characterization, Biosynthesis, Bioactivities, Molecular Docking, and Molecular Dynamics

“…They are produced by various basidiomycetous and ascomycetous fungi, including Chaetomium, Penicillium, Aspergillus, Talaromyces, Phomopsis, Monascus, Emericella, Epicoccum, Hypoxylon, and Pestalotiopsis, where they are accountable for the green, red, or yellow color of mycelia and/or fruiting bodies [23]. They possess myriad bioactivities: antitumor, cytotoxic, antimicrobial, anti-inflammatory, antioxidant, enzyme inhibitory, antiviral, insecticidal, and antileishmanial [24]. Chaetomugilins and closely related chaetoviridins are azaphilones featuring a C-7-methyl group and C-5 chlorineexcept for chaetomugilins T (29) and U (30)-and a C-3-branched pentenyl chain (Figure 1).…”