Enhanced Cytotoxicity and Antimelanoma Activity of Novel Semisynthetic Derivatives of Betulinic Acid with Indole Conjugation DOI Creative Commons
Adelina Lombrea, Claudia Watz, Larisa Bora

et al.

Plants, Journal Year: 2023, Volume and Issue: 13(1), P. 36 - 36

Published: Dec. 21, 2023

The prevalence and severity of skin cancer, specifically malignant melanoma, among Caucasians remains a significant concern. Natural compounds from plants have long been explored as potential anticancer agents. Betulinic acid (BI) has shown promise in its therapeutic properties, including effects. However, limited bioavailability hindered medicinal applications. To address this issue, two recently synthesized semisynthetic derivatives, N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) N-(2,3-indolo-betulinoyl)glycylglycine (BA2), were compared with previously reported N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic (BA4), BI. These evaluated for their effects on murine melanoma cells (B164A5) using various vitro assays. introduction an indole framework at the C2 position BI resulted increased cytotoxicity. Furthermore, cytotoxicity compound BA4 was enhanced by conjugating carboxylic group amino residue. BA2 BA3, glycine glycylglycine residues C28, exhibited approximately 2.20-fold higher inhibitory activity to BA4. safety assessment human keratinocytes (HaCaT) revealed that concentrations up 10 µM slightly reduced cell viability, while 75 lower viability rates. LDH leakage assays confirmed membrane damage B164A5 when exposed tested compounds. BA3 highest release, indicating strong NR assay dose-dependent lysosome disruption BA1, BA2, showing most cytotoxic Scratch demonstrated concentration-dependent inhibition migration, being effective. Hoechst 3342 staining induced apoptosis, necrosis concentrations, confirming anti-melanoma properties. In conclusion, derivatives BI, particularly show candidates further research developing effective anti-cancer therapies.

Language: Английский

Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials DOI Creative Commons
Xin Xie, Tingting Yu, Xiang Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 6, 2023

Abstract Undruggable proteins are a class of that often characterized by large, complex structures or functions difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also great opportunity for treatment human diseases and attracted substantial efforts in the field medicine. Therefore, this review, we focus on recent development discovery targeting “undruggable” their application clinic. To make review well organized, discuss strategies proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction targeted nucleic acid-based approach, immunotherapy others.

Language: Английский

Citations

163
Organocatalytic asymmetric cascade bicyclization: access to chiral polycyclic bisindoles from 2-indolylmethanols and propargylic alcohols DOI
Wen-Run Zhu, Qiong Su, Xiaoyi Deng

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(7), P. 2040 - 2046

Published: Jan. 1, 2024

A chiral phosphoric acid-catalyzed asymmetric bis-cyclization of α-indolyl propargylic alcohols with 2-indolylmethanols was realized.

Language: Английский

Citations

5
Visible-light-mediated substituent-controlled regiodivergent (2 + 2)/(3 + 2) cycloadditions for the synthesis of aza-analogs of β-lactam and γ-fused lactam derivatives DOI

Wei‐Fang Zuo,

Yang Zhang,

Yulin Luo

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(13), P. 3576 - 3582

Published: Jan. 1, 2024

Substituent-controlled regiodivergent synthesis of aza-analogs β-lactam and γ-fused lactam derivatives via the visible-light-induced Wolff rearrangement α-diazoketones azo esters.

Language: Английский

Citations

4
Enantioselective Synthesis of N-Substituted Indoles with α,β-Stereocenters via Sequential Aza-Piancatelli/Cyclization Reactions DOI

Kaijun Xie,

Xukun Nie,

Pengfei Zhou

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

A sequence of catalytic asymmetric aza-Piancatelli rearrangement and Pd-catalyzed cyclization has been developed to construct chiral N-substituted indoles featuring α,β-consecutive stereocenters. This indole framework, bearing α,β-chiral centers, is a prevalent structural motif in natural products biologically active molecules, yet enantioselective methods for its preparation remain scarce. protocol offers efficient access diverse array derivatives with stereocenters, achieving high yields excellent enantioselectivities.

Language: Английский

Citations

0
Cu-catalyzed reductive Friedel-Crafts alkylation of indoles with ketones for one-pot synthesis of 3-substituted indoles DOI

Wengang Wang,

Zewei Mao

Journal of Organometallic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 123513 - 123513

Published: Jan. 1, 2025

Language: Английский

Citations

0
Discovery of tri(indolyl)methanes as potent and selective inhibitors against human carboxylesterase 2 DOI
Weiran Li, Jie Mu, Anqi Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 307, P. 141868 - 141868

Published: March 9, 2025

Language: Английский

Citations

0
Catalyst-controlled regiodivergence and stereodivergence in formal cross-[4+2] cycloadditions: The unique effect of bismuth(III) DOI
Qiumeng Hou,

Chenxi Cai,

Shuai‐Jiang Liu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 26, 2025

The [4+2] cycloaddition is crucial for constructing six-membered rings in pharmaceuticals and natural products. Cross-[4+2] cycloadditions offer greater product diversity than traditional diene-dienophile reactions due to multiple possible pathways. However, precise control over regio- stereoselectivity various isomers remains a great challenge. This study reports catalyst-controlled regiodivergent formal cross-cycloadditions of acyclic dienes enones, significantly enhancing access diverse pyrazole-fused spirooxindoles. Chiral phosphoric acid (CPA) catalysis enables endoselective cycloadditions, while Bi(III) with CPA ligand yields [2+4] products high stereoselectivity. A Claisen rearrangement the adduct produces exo-selective product, further increasing stereochemical enabling synthesis six stereo-isomers from single substrate set. DFT calculations reveal that reverses regioselectivity by repositioning reactants pocket stabilizing enone oxygen’s negative charge. In addition, 3as demonstrates therapeutic potential against triple-negative breast cancer, an IC 50 8.5 μM MDA-MB-453 cells.

Language: Английский

Citations

0
Regio- and Enantioselective N-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel-Crafts Alkylation DOI Creative Commons
Vojtěch Dočekal,

Yaroslava Niderer,

Adam Kurčina

et al.

Published: June 21, 2024

Chiral annulated indoles are unique molecules with numerous examples of this structural motif in natural and medicinally relevant compounds. However, accessing these enantioenriched molecules, particularly on the benzene ring, has been limited often overlooked. This study presents a highly efficient organocatalytic protocol for synthesizing chiral indoles. The efficiency developed methodology is demonstrated by its broad substrate scope, excellent functional group tolerance, use only 1 mol% conjugated acid catalyst. Additionally, observed regioselectivity, gram-scale reaction, various follow-up transformations underscore potential method.

Language: Английский

Citations

2
Regio- and Enantioselective N-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel–Crafts Alkylation DOI Creative Commons
Vojtěch Dočekal,

Yaroslava Niderer,

Adam Kurčina

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(33), P. 6993 - 6998

Published: Aug. 8, 2024

Chiral indoles annulated on the benzene ring are unique and significant in natural medicinal compounds. However, accessing these enantioenriched molecules has often been overlooked. The present study introduces an organocatalytic protocol to access compounds efficiently, demonstrated by substrate scope, functional group tolerance, using only 1 mol % of a chiral conjugated acid catalyst. Additionally, explores regioselectivity, gram-scale reactions, follow-up transformations, underscoring method's potential.

Language: Английский

Citations

2
Construction of the Akuammiline Alkaloid Core Structure via Stereoselective E-Ring Formation DOI
Naoki Hashimoto, Junichi Taguchi,

Takumi Kasagi

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(14), P. 10388 - 10392

Published: July 2, 2024

Construction of the core structure akuammiline alkaloids with three-dimensional cage-like structures for their diversity-oriented synthesis was investigated. Extensive exploration centered around introduction nitrogen functional groups and construction E-ring in an intramolecular or intermolecular manner revealed that a Claisen rearrangement approach involving amination provided common precursor, potentially facilitating divergent access to various types alkaloids.

Language: Английский

Citations

0