Stephacidin A and B are antitumor alkaloids isolated from the fungus Aspergillus ochraceus[1] that belong to a class of naturally occurring 2,5-diketopiperazines.[2] This unusual family of fungal metabolites are complex bridged 2,5-diketopiperazine alkaloids that possess a unique bicyclo[2.2.2]diazaoctane core ring system and are constituted mainly from tryptophan, proline, and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cyclized across the α-carbon atoms of a 2,5-diketopiperazine ring. The molecular architecture of stephacidin B, formally a dimer [3] of avrainvillamide, reveals a complex dimeric prenylated N-hydroxyindole alkaloid that contains 15 rings and 9 stereogenic centers and is one of the most complex indole alkaloids isolated from fungi. Stephacidin B rapidly converts into the electrophilic monomer avrainvillamide in cell culture, and there is evidence that the monomer avrainvillamide interacts with intracellular thiol-containing proteins, most likely by covalent modification.[4]
Structures of Stephacidin B and Stephacidin AConversion of dimer Stephacidin B to monomer Avrainvillamide
Avrainvillamide, which contains a 3-alkylidene-3H-indole 1-oxide function, was identified in culture media from various strains of Aspergillus and is reported to exhibit antimicrobial activity against multidrug-resistant bacteria.[5] The avrainvillamide and stephacidins family of structurally complex anticancer natural products are active against the human colon HCT 116 cell line.[6] The signature bicyclo[2.2.2]diazaoctane ring system common to these alkaloids has inspired numerous synthetic approaches.[7]
Referencesedit
^Qian-Cutrone J, Huang S, Shu YZ, Vyas D, Fairchild C, Menendez A, Krampitz K, Dalterio R, Klohr SE, Gao Q (December 2002). "Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells". Journal of the American Chemical Society. 124 (49): 14556–14557. doi:10.1021/ja028538n. PMID 12465964.
^Borthwick AD (2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews. 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
^von Nussbaum F (2003). "Stephacidin B-A new stage of complexity within prenylated indole alkaloids from fungi". Angewandte Chemie International Edition. 42 (27): 3068–3071. doi:10.1002/anie.200301646. PMID 12866092.
^Wulff JE, Herzon SB, Siegrist R, Myers AG (April 2007). "Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell culture". Journal of the American Chemical Society. 129 (16): 4898–4899. doi:10.1021/ja0690971. PMC3175819. PMID 17397160.
^Sugie Y, Hirai H, Inagaki T, Ishiguro M, Kim YJ, Kojima Y, Sakakibara T, Sakemi S, Sugiura A, Suzuki Y, Brennan L (2001). "A new antibiotic CJ-17,665 from Aspergillus ochraceus". The Journal of Antibiotics. 54 (11): 911–916. doi:10.7164/antibiotics.54.911. PMID 11827033.
^Baran PS, Hafensteiner BD, Ambhaikar NB, Guerrero CA, Gallagher JD (July 2006). "Enantioselective total synthesis of avrainvillamide and the stephacidins". Journal of the American Chemical Society. 128 (26): 8678–8693. doi:10.1021/ja061660s. PMID 16802835.
^Escolano C (December 2005). "Stephacidin B, the avrainvillamide dimer: A formidable synthetic challenge". Angewandte Chemie International Edition. 44 (47): 7670–7673. doi:10.1002/anie.200502383. PMID 16252300.
External linksedit
Stephacidin A and B: two structurally novel, selective inhibitors of the testosterone-dependent prostate LNCaP cells
PubChem - Stephacidin A
PubChem - C6-epi-Stephacidin A
PubChem - Stephacidin B
May 01, 2024
stephacidin, antitumor, alkaloids, isolated, from, fungus, aspergillus, ochraceus, that, belong, class, naturally, occurring, diketopiperazines, this, unusual, family, fungal, metabolites, complex, bridged, diketopiperazine, alkaloids, that, possess, unique, b. Stephacidin A and B are antitumor alkaloids isolated from the fungus Aspergillus ochraceus 1 that belong to a class of naturally occurring 2 5 diketopiperazines 2 This unusual family of fungal metabolites are complex bridged 2 5 diketopiperazine alkaloids that possess a unique bicyclo 2 2 2 diazaoctane core ring system and are constituted mainly from tryptophan proline and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cyclized across the a carbon atoms of a 2 5 diketopiperazine ring The molecular architecture of stephacidin B formally a dimer 3 of avrainvillamide reveals a complex dimeric prenylated N hydroxyindole alkaloid that contains 15 rings and 9 stereogenic centers and is one of the most complex indole alkaloids isolated from fungi Stephacidin B rapidly converts into the electrophilic monomer avrainvillamide in cell culture and there is evidence that the monomer avrainvillamide interacts with intracellular thiol containing proteins most likely by covalent modification 4 Structures of Stephacidin B and Stephacidin A Conversion of dimer Stephacidin B to monomer Avrainvillamide Avrainvillamide which contains a 3 alkylidene 3H indole 1 oxide function was identified in culture media from various strains of Aspergillus and is reported to exhibit antimicrobial activity against multidrug resistant bacteria 5 The avrainvillamide and stephacidins family of structurally complex anticancer natural products are active against the human colon HCT 116 cell line 6 The signature bicyclo 2 2 2 diazaoctane ring system common to these alkaloids has inspired numerous synthetic approaches 7 References edit Qian Cutrone J Huang S Shu YZ Vyas D Fairchild C Menendez A Krampitz K Dalterio R Klohr SE Gao Q December 2002 Stephacidin A and B two structurally novel selective inhibitors of the testosterone dependent prostate LNCaP cells Journal of the American Chemical Society 124 49 14556 14557 doi 10 1021 ja028538n PMID 12465964 Borthwick AD 2012 2 5 Diketopiperazines Synthesis Reactions Medicinal Chemistry and Bioactive Natural Products Chemical Reviews 112 7 3641 3716 doi 10 1021 cr200398y PMID 22575049 von Nussbaum F 2003 Stephacidin B A new stage of complexity within prenylated indole alkaloids from fungi Angewandte Chemie International Edition 42 27 3068 3071 doi 10 1002 anie 200301646 PMID 12866092 Wulff JE Herzon SB Siegrist R Myers AG April 2007 Evidence for the rapid conversion of stephacidin B into the electrophilic monomer avrainvillamide in cell culture Journal of the American Chemical Society 129 16 4898 4899 doi 10 1021 ja0690971 PMC 3175819 PMID 17397160 Sugie Y Hirai H Inagaki T Ishiguro M Kim YJ Kojima Y Sakakibara T Sakemi S Sugiura A Suzuki Y Brennan L 2001 A new antibiotic CJ 17 665 from Aspergillus ochraceus The Journal of Antibiotics 54 11 911 916 doi 10 7164 antibiotics 54 911 PMID 11827033 Baran PS Hafensteiner BD Ambhaikar NB Guerrero CA Gallagher JD July 2006 Enantioselective total synthesis of avrainvillamide and the stephacidins Journal of the American Chemical Society 128 26 8678 8693 doi 10 1021 ja061660s PMID 16802835 Escolano C December 2005 Stephacidin B the avrainvillamide dimer A formidable synthetic challenge Angewandte Chemie International Edition 44 47 7670 7673 doi 10 1002 anie 200502383 PMID 16252300 External links editStephacidin A and B two structurally novel selective inhibitors of the testosterone dependent prostate LNCaP cells PubChem Stephacidin A PubChem C6 epi Stephacidin A PubChem Stephacidin B Retrieved from https en wikipedia org w index php title Stephacidin amp oldid 1049295489, wikipedia, wiki, book, books, library,
