Novel Indole Compounds as TEAD Inhibitors for Treating Cancer

Enzymatic reactions in teleocidin B biosynthesis

Journal of Natural Medicines ◽

10.1007/s11418-021-01504-2 ◽

2021 ◽

Author(s):

Takayoshi Awakawa

Keyword(s):

Structural Biology ◽

Bond Formation ◽

Enzymatic Reactions ◽

New Developments ◽

Indole Compounds ◽

Kinase C ◽

Biological Studies ◽

New Knowledge ◽

Primary Focus ◽

Activate Protein Kinase

AbstractThe teleocidin B family members are terpene indole compounds isolated from Streptomyces bacteria, and they strongly activate protein kinase C (PKC). Their unique structures have attracted many researchers in the natural product chemistry and pharmacology fields, and numerous isolation and bioactivity studies have been conducted. The accumulated information has facilitated the identification of the enzymatic reactions in teleocidin biosynthesis, and new developments in structural biology have strongly aided efforts to clarify the finer points of these reactions. This review describes the recent biochemical and structural biological studies to reveal their reaction mechanisms, with a primary focus on the terpene cyclization triggered by the C-N bond formation by P450 oxygenase (TleB), the prenyltransferase (TleC), and the methyltransferase (TleD). This new knowledge will benefit future engineering studies to create unnatural PKC activators.

Download Full-text

Engineered RebH halogenase variants demonstrating a specificity switch from tryptophan towards novel indole compounds

ChemBioChem ◽

10.1002/cbic.202100210 ◽

2021 ◽

Author(s):

Barindra Sana ◽

Timothy Ho ◽

Srinivasaraghavan Kannan ◽

Ding Ke ◽

Eunice Li ◽

...

Keyword(s):

Indole Compounds

Download Full-text

Physiologically Active Compounds in Four Species of Phellinus

Natural Product Communications ◽

10.1177/1934578x1701200313 ◽

2017 ◽

Vol 12 (3) ◽

pp. 1934578X1701200 ◽

Cited By ~ 14

Author(s):

Katarzyna Sułkowska-Ziaja ◽

Anna Maślanka ◽

Agnieszka Szewczyk ◽

Bożena Muszyńska

Keyword(s):

Phenolic Acids ◽

High Performance ◽

Total Content ◽

Dry Weight ◽

Hplc Method ◽

Indole Compounds ◽

Methanolic Extracts ◽

Free Phenolic Acids ◽

Layer Chromatography ◽

Physiologically Active Compounds

The content of two groups of compounds with biological activity (non-hallucinogenic indole compounds and free phenolic acids) were analyzed in extracts of fruiting bodies of four species of Phellinus: P. igniarius, P. pini, P. pomaceus and P. robustus. The presence of indole compounds in methanolic extracts was analyzed by high-performance liquid chromatography and thin-layer chromatography coupled with densitometric detection. Three metabolites (serotonin, tryptamine, and L-tryptophan) were identified. The contents of individual indole compounds ranged from 1.70 (tryptamine in P. robustus) to 8.32 mg x 100 g1 dry weight (L-tryptophan in P. robustus). Four free phenolic acids were detected in methanolic extracts by the HPLC method. The total content ranged from 9.9 mg x 100 g1 DW (P. igniarius) to 32.5 mg x 100 g1 DW (P. robustus).

Download Full-text

Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

Molecules ◽

10.3390/molecules26154414 ◽

2021 ◽

Vol 26 (15) ◽

pp. 4414

Author(s):

Fabiana Sélos Guerra ◽

Flaviana Rodrigues Fintelman Dias ◽

Anna Claudia Cunha ◽

Patricia Dias Fernandes

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Cancer Cell Line ◽

Caspase 9 ◽

Apoptosis Pathway ◽

Indole Compounds ◽

Intrinsic Apoptosis Pathway ◽

Ros Accumulation

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation.

Download Full-text