Chaetocin (Mao Kesu)

1. Core Information[1]

Chinese Name (pinyin): Mao Kesu
English Name: Chaetocin A
CAS No.: 28097-03-2
Molecular Formula: C30H28N6O6S4
Molecular Weight: 696.8 g/mol
SMILES:CN1C(=O)C23CC4(C(N2C(=O)C1(SS3)CO)NC5=CC=CC=C54)C67CC89C(=O)N(C(C(=O)N8C6NC1=CC=CC=C71)(SS9)CO)C

 

2. International Nomenclature & Identifiers

2.1 IUPAC Name

(1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-18-methyl-13,17-dioxo-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-trien-3-yl]-18-methyl-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-triene-13,17-dione

2.2 InChI

InChI=1S/C30H28N6O6S4/c1-33-21(39)27-11-25(15-7-3-5-9-17(15)31-19(25)35(27)23(41)29(33,13-37)45-43-27)26-12-28-22(40)34(2)30(14-38,46-44-28)24(42)36(28)20(26)32-18-10-6-4-8-16(18)26/h3-10,19-20,31-32,37-38H,11-14H2,1-2H3/t19-,20-,25+,26+,27+,28+,29+,30+/m1/s1

2.3 InChlKey

PZPPOCZWRGNKIR-PNVYSBBASA-N

2.4 Canonical SMILES

CN1C(=O)C23CC4(C(N2C(=O)C1(SS3)CO)NC5=CC=CC=C54)C67CC89C(=O)N(C(C(=O)N8C6NC1=CC=CC=C71)(SS9)CO)C

2.5 Isomeric SMILES

CN1C(=O)[C@@]23C[C@]4([C@@H](N2C(=O)[C@@]1(SS3)CO)NC5=CC=CC=C54)[C@]67C[C@]89C(=O)N([C@](C(=O)N8[C@H]6NC1=CC=CC=C71)(SS9)CO)C

 

 

 

3. Spectroscopic Data

3.1 ¹³C Nuclear Magnetic Resonance (¹³C NMR)

 

3.2 ¹H Nuclear Magnetic Resonance (¹H NMR)

 

4. Research Progress on Chaetocin

Chaetocin is a natural metabolite from Chaetomium species with diverse biological and pharmacological activities. Key advances include:

 

 

4.1 Anticancer Mechanisms

Chaetocin inhibits the histone methyltransferase SUV39H1, exerting activity against leukemia, myeloma, and notably solid tumors. It modulates oncogenic signaling, induces apoptosis, enhances autophagy, triggers cell-cycle arrest, and suppresses angiogenesis. In triple-negative breast cancer cells (MDA-MB-231), chaetocin synergizes with doxorubicin, lowering H3K9me3 levels and activating apoptotic pathways.

4.2 Effects on Somatic Cell Nuclear Transfer Embryos

Treating Debao pig fetal fibroblasts with chaetocin enhances nuclear transfer embryo development and reduces H3K9me3 expression.

4.3 Modern Taxonomy of Chaetomiaceae

Phylogenetic studies confirm Chaetomiaceae as monophyletic but reveal polyphyly among several genera, prompting redefinition of 15 taxa and establishment of the new family Podosporaceae.

4.4 Broad-Spectrum Antifungal and Nematicidal Activity

Chaetocin shows broad activity against more than 40 agricultural and foodborne pathogenic fungi, outperforming reference fungicides in many cases, and exhibits nematicidal properties.

4.5 Secondary Metabolites & Bioactivity

Chaetomium fungi produce over 300 characterized metabolites spanning diverse scaffolds with cytotoxic, anti-inflammatory, and antimicrobial properties—rich reservoirs for drug leads.

 

4.6 Apoptosis Induction & Macrophage Activation

Chaetocin promotes ROS accumulation, activating the JNK/c-Jun pathway to induce apoptosis in colorectal cancer cells and enhance macrophage phagocytosis.

4.7 Histone Lysine Methyltransferase Inhibition

Chaetocin irreversibly inhibits HKMT G9a via its unique epipolythiodioxopiperazine (ETP) core, causing time-dependent enzyme inactivation and protein denaturation.

Collectively, chaetocin’s anticancer, developmental, antifungal, and immunomodulatory activities highlight its promise as a future therapeutic lead.

 

 

 

 

References