Chetomin (Mao Kejun Suan)

1. Core Information[1]

Chinese Name (pinyin): Mao Kejun Suan
English Name: Chetomin
CAS No.: 1403-36-7
Molecular Formula: C31H30N6O6S4
Molecular Weight: 710.9 g/mol
SMILES:CN1C(=O)C2(N(C(=O)C1(SS2)CC3=CN(C4=CC=CC=C43)C56CC78C(=O)N(C(C(=O)N7C5NC9=CC=CC=C69)(SS8)CO)C)C)CO

 

2. International Nomenclature & Identifiers

2.1 IUPAC Name

(1S,3S,11R,14S)-14-(hydroxymethyl)-3-[3-[[(1S,4S)-4-(hydroxymethyl)-5,7-dimethyl-6,8-dioxo-2,3-dithia-5,7-diazabicyclo[2.2.2]octan-1-yl]methyl]indol-1-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/C31H30N6O6S4/c1-33-25(42)30(15-38)34(2)23(40)28(33,44-46-30)12-17-13-36(21-11-7-4-8-18(17)21)27-14-29-24(41)35(3)31(16-39,47-45-29)26(43)37(29)22(27)32-20-10-6-5-9-19(20)27/h4-11,13,22,32,38-39H,12,14-16H2,1-3H3/t22-,27+,28+,29+,30+,31+/m1/s1

2.3 InChlKey

ZRZWBWPDBOVIGQ-YWZWRZHGSA-N

2.4 Canonical SMILES

CN1C(=O)C2(N(C(=O)C1(SS2)CC3=CN(C4=CC=CC=C43)C56CC78C(=O)N(C(C(=O)N7C5NC9=CC=CC=C69)(SS8)CO)C)C)CO

2.5 Isomeric SMILES

CN1C(=O)[C@]2(N(C(=O)[C@@]1(SS2)CC3=CN(C4=CC=CC=C43)[C@]56C[C@]78C(=O)N([C@](C(=O)N7[C@H]5NC9=CC=CC=C69)(SS8)CO)C)C)CO

 

 

 

3. Spectroscopic Data

3.1 ¹³C Nuclear Magnetic Resonance (¹³C NMR)

 

3.2 ¹H Nuclear Magnetic Resonance (¹H NMR)

 

4. Research Progress on Chetomin

Chetomin is a metabolite isolated from Chaetomium globosum that disrupts the Hsp90/HIF1α signaling axis.

 

 

4.1 Antitumor Activity

Chetomin potently targets non-small-cell lung cancer (NSCLC) stem cells by blocking Hsp90/HIF1α signaling. It suppresses sphere formation at nanomolar concentrations and inhibits proliferation of both chemosensitive and resistant NSCLC cells at micromolar levels. In mouse models, chetomin markedly reduces NSCLC tumor formation without observable toxicity at tested doses.

4.2 Immunosuppressive Effects

Chetomin inhibits B- and T-cell proliferation, with IC₅₀ values of 0.09 μg/mL for LPS-stimulated BALB/c splenic B lymphocytes and 0.17 μg/mL for Con A–stimulated T lymphocytes.

4.3 Biosynthetic Insights

Recent studies have mapped the chetomin biosynthetic pathway, highlighting glutathione S-transferase CheG and nonribosomal peptide synthetase CheP as critical enzymes. Supplementing cultures with glutathione (GSH) enhances chetomin yield by roughly 15-fold.

4.4 Structure–Activity Relationships

SAR analyses reveal that polysulfide-bridged analogues display greater cytotoxicity than disulfide-bridged counterparts. 6-Formamide-chetomin exhibits low-nanomolar potency against HeLa, SGC-7901, and A549 cell lines.

4.5 Activity Against Resistant Pathogens

Chetomin exhibits strong activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration of 0.05 μg/mL—substantially lower than vancomycin’s 0.625 μg/mL. Overall, chetomin’s multifaceted profile across oncology, immunomodulation, and anti-resistance applications positions it as a compelling candidate for further investigation and biosynthetic optimization.

 

 

 

References