Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by .
10.1016/j.apsb.2018.09.011
- Author:
Liping LIN
1
;
Nan JIANG
2
;
Huimin WU
3
;
Yaning MEI
4
;
Jie YANG
5
;
Renxiang TAN
1
Author Information
1. State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
2. School of Pharmacy, Nanjing Medical University, Nanjing 210029, China.
3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023 China.
4. Department of Clinical Laboratory, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
5. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China.
- Publication Type:Journal Article
- Keywords:
8-Amino-7-oxononanoate synthase;
Antibacterial;
Anticancer;
Daldinia eschscholzii;
Decarboxylative Claisen condensation;
Indole-3-carbinol;
Polyketide-indole hybrids
- From:
Acta Pharmaceutica Sinica B
2019;9(2):369-380
- CountryChina
- Language:English
-
Abstract:
Two skeletally undescribed polyketide-indole hybrids (PIHs), named indolchromins A and B, were generated from indole-3-carbinol (I3C) in the fungal culture (). The indolchromin structures were elucidated mainly by their 1D and 2D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism (CD) spectra with the electronic CD (ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions, including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase (AONS), C()-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3-8.6 μmol/L, (2,4)- and (2,4)-indolchromin A and (2,4)-indolchromin B are inhibitory against , , sp., , and . (2,4)-Indolchromin A and (2,4)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC values of 27.9 and 131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7 (IC 94.4 nmol/L).