Article
Biochemistry & Molecular Biology
Ju Chen, Yunran Xu, Yan Yang, Xin Yao, Yuan Fu, Yi Wang, Yunjun Liu, Xiuzhen Wang
Summary: In this study, a series of glycyrrhetic acid derivatives were synthesized and their cytotoxicity against tumor cells was investigated. Compound 3a showed high antiproliferative activity against HeLa cells and its mechanism of action was explored through various assays. The results demonstrated that compound 3a could block the cell cycle, inhibit cell migration, induce apoptosis, and affect the expression of mitochondria-related proteins. This work provides valuable insights for the development of glycyrrhetinic acid compounds as potential anticancer molecules.
Article
Biochemistry & Molecular Biology
Panpan Wu, Borong Tu, Jinfeng Liang, Shengzhu Guo, Nana Cao, Silin Chen, Zhujun Luo, Jiahao Li, Wende Zheng, Xiaowen Tang, Dongli Li, Xuetao Xu, Wenfeng Liu, Xi Zheng, Zhaojun Sheng, Adam P. Roberts, Kun Zhang, Weiqian David Hong
Summary: A series of triterpenoid derivatives, including ursolic acid (UA), oleanolic acid (OA), and 18β-glycyrrhetinic acid (GA), were synthesized with various substituted aromatic side chains at the C-2 position. Among them, the GA derivative with aromatic side chains showed potent antibacterial activity against drug sensitive and resistant S. aureus, indicating potential for development of a new type of triterpenoid antibacterial agent.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Bo-Wen Pan, Liang-Liang Zheng, Yang Shi, Zhang-Chao Dong, Ting-Ting Feng, Jian Yang, Ying Wei, Ying Zhou
Summary: Novel derivatives of 18 beta-glycyrrhetinic acid were synthesized by introducing aromatic or heterocyclic structures to enhance their interaction with target proteins. These compounds exhibited significant inhibitory effects on HIV-1 protease and cancer cells, suggesting their potential as anti-HIV and anticancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Marius Mioc, Alexandra Prodea, Roxana Racoviceanu, Alexandra Mioc, Roxana Ghiulai, Andreea Milan, Mirela Voicu, Gabriel Mardale, Codruta Soica
Summary: This paper summarizes the recent studies on the mechanism of action of several triterpenic acids, which have various biological activities and are important for drug development and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yilin Xu, Min Wang, Shuangcheng Ning, Zhonglan Yang, Lili Zhou, Xinhua Xia
Summary: This study aimed to design solid lipid nanoparticles (SLNs) modified with glycyrrhetinic acid (GA) and/or folate (FA) to encapsulate cantharidin (CTD) for targeting hepatocellular carcinoma (HCC). The results showed that GA-FA-CSLNs and FA-CSLNs had stronger inhibitory effects on HCC cells, lower cytotoxicity and hemolysis, and increased inhibition of cell migration and apoptosis. The cell cycle analysis indicated cell arrest mainly in the S phase and G2/M phase. Competition suppression assays confirmed targeted effects on HCC cells. In vivo tumor suppression assays demonstrated excellent tumor inhibition rates for GA-FA-CSLNs and FA-CSLNs. These SLNs have promising potential for therapeutic intervention in HCC.
Article
Medicine, Research & Experimental
Xu-Wang Pan, Jin-Song Huang, Shou-Rong Liu, Yi-Dan Shao, Jian-Jun Xi, Ruo-Yu He, Ting-Ting Shi, Rang-Xiao Zhuang, Jian-Feng Bao
Summary: The study investigated the liver-targeting and anti-liver cancer efficacy of ART/GA-PEG-PLGA NPs. The results showed that GA-coated NPs significantly increased hepatoma-targeted cellular uptake, and ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Overall, ART/GA-PEG-PLGA NPs demonstrated excellent hepatoma-targeted delivery and anti-liver cancer efficacy, making them a promising strategy for treating liver cancer.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Dominik Langer, Barbara Wicher, Wioletta Bendzinska-Berus, Barbara Bednarczyk-Cwynar, Ewa Tykarska
Summary: This study reports the synthesis and structural characterization of new esters of oleanolic acid and its 11-oxo derivatives. The compounds crystallize in four isostructural groups, with each group containing one to four structures. Single-crystal X-ray analysis reveals that molecules in non-isostructural groups self-assemble according to two schemes, which also describe supramolecular architectures in crystals of glycyrrhetinic acid derivatives. The formation of structural motifs is attributed to van der Waals forces. Parameters introduced for the analysis of one- and two-dimensional assemblies enable the comparison of motifs in isostructural and non-isostructural crystals, including polymorphs, and the qualitative assessment of differences in molecular self-assembly. One-, two- or three-dimensional similarity has been confirmed using XPac calculations.
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Jiyoung Kim, Sanghee Lee, Kun Na
Summary: A novel photosensitizer designed for liver cancer treatment using glycyrrhetinic acid has demonstrated significant therapeutic efficacy in liver cancer cells. The modified photosensitizer effectively accumulates in liver cancer and shows a tumor growth inhibition effect, suggesting its potential to alter conventional liver cancer treatment methods.
Article
Plant Sciences
Yuan Feng, Yanwu Li, Di Zhou, Bingxin Li, Gang Chen, Ning Li
Summary: Antibiotics can induce intestinal epithelial injury through HuR, while GA can exert a protective effect on AIJ by restoring HuR levels.
Article
Chemistry, Multidisciplinary
Hong Y. Pan, Qing Q. Wu, Qiao Q. Yin, Yi N. Dai, Yi C. Huang, Wei Zheng, Tian C. Hui, Mei J. Chen, Ming S. Wang, Jia J. Zhang, Hai J. Huang, Yong X. Tong
Summary: Chronic hepatitis B virus infection is a primary risk factor for hepatocellular carcinoma development. This study used LC-MS to analyze serum metabolic profiles of CHB, LC, and HCC patients, identifying metabolites that change with liver disease progression. Certain metabolites, such as TCA and eicosapentaenoic acid, were found to have diagnostic performance with liver disease progression and are correlated with AFP levels and age.
Article
Biochemistry & Molecular Biology
Rui Fan, Yanxiang Gao
Summary: The study found that the Maillard reaction increased antioxidant activity in subcritical water extraction, and the behaviors and kinetic parameters of different reactions were analyzed. Furthermore, the degree of the Maillard reaction increased with the rise of extraction temperature.
Article
Biochemistry & Molecular Biology
Lidia Diaz-Sanchez, Alejandro Zentella-Dehesa, Victor Alberto Castro-Torres, Noemi Silva-Jimenez, Nadia Judith Jacobo-Herrera, Mariano Martinez-Vazquez
Summary: The combination of AMD or 3 alpha OH-AMD acids with CDDP exhibited increased cytotoxic effect in PC3 prostate and HCT116 colon cancer cells, but showed no additional activity in in vivo tests. Furthermore, the combinations of 3 alpha OH-AMD and CDDP exerted antagonistic effects in both cell types.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Polymer Science
Essraa A. Hassan, Rania M. Hathout, Heba A. Gad, Omaima A. Sammour
Summary: This study successfully formulated multi-purpose zein nanoparticles, including passively and actively targeted systems, and demonstrated superior anti-hepatocellular carcinoma activity compared to free drug.
EUROPEAN POLYMER JOURNAL
(2022)
Article
Plant Sciences
Jinfeng Shi, Jingjing Li, Jiaxin Li, Renkai Li, Xiaoping Wu, Fei Gao, Liang Zou, Winston Wing Shum Mak, Chaomei Fu, Jinming Zhang, George Pak-Heng Leung
Summary: The study optimized the drug ratio of glycyrrhetinic acid (GA) and doxorubicin (Dox) to enhance the anti-cancer effect against MCF-7 breast cancer cells, showing significant improvements in cytotoxicity, apoptosis, and mitochondrial membrane potential loss. The addition of GA increased Dox accumulation in cells and the combination inhibited HUVECs proliferation, migration, and tube formation through down-regulation of the VEGFR2-mediated pathway, indicating a promising synergistic anti-angiogenesis effect. In a mouse breast tumor model, the combination of Dox with GA demonstrated enhanced anti-tumor efficacy and reduced cardiotoxicity from Dox.
Review
Pharmacology & Pharmacy
Changchao Huan, Yao Xu, Wei Zhang, Tingting Guo, Haochun Pan, Song Gao
Summary: Liquorice, a traditional medicine, contains triterpenoids such as glycyrrhizin and glycyrrhetinic acid which have inhibitory effects on various viruses, including SARS-CoV-2. These compounds work through mechanisms such as inhibition of virus replication, direct inactivation of viruses, and inhibition of inflammation. Further research on unknown antiviral mechanisms, structural modifications, and drug combinations is emphasized for future studies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Niels Heise, Sander Friedrich, Veronika Temml, Daniela Schuster, Bianka Siewert, Rene Csuk
Summary: The study demonstrated that the acetylated triterpenoic acids could effectively inhibit the enzyme butyrylcholinesterase (BChE) while showing weak inhibition for acetylcholinesterase (AChE). Enzyme kinetics evaluation revealed hyperbolic inhibition for BChE, and molecular modeling explained the selectivity between AChE and BChE for these compounds.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Jixing Lai, Chen Yang, Rene Csuk, Baoan Song, Shengkun Li
Summary: The first palladium-catalyzed asymmetric addition of arylboronic acids to coumarins has been successfully developed, providing a straightforward and asymmetric approach for the synthesis of pharmaceutically important 4-aryl-3,4-dihydrocoumarins. This methodology employs easily accessible and stable ligands, has a broad substrate scope, can be conducted under mild reaction conditions, and allows for the accommodation of electron-withdrawing arylboronic acids.
Article
Chemistry, Physical
Satya Kumar Avula, Saeed Ullah, Sobia Ahsan Halim, Ajmal Khan, Muhammad U. Anwar, Rene Csuk, Ahmed Al-Harrasi
Summary: In this study, 26 compounds of substituted quinoline derivatives were synthesized and their alpha-glucosidase inhibition activity was investigated. Most of the synthesized compounds showed good inhibitory activity against alpha-glucosidase, and some exhibited very promising results. Compound 12's structure was confirmed through single crystal X-ray diffraction. The study revealed a new series of substituted quinoline derivatives as potential inhibitors of alpha-glucosidase.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Toni C. Denner, Niels Heise, Julian Zacharias, Oliver Kraft, Sophie Hoenke, Rene Csuk
Summary: Acetylated triterpenoids were transformed into succinyl-spacered acetazolamide conjugates and tested for their inhibitory actvity on carbonic anhydrase II and cytotoxicity on human tumor cell lines and non-malignant fibroblasts. The conjugates derived from betulin and glycyrrhetinic acid showed the strongest inhibition, while those derived from ursolic or oleanolic acid were weaker inhibitors but had lower cytotoxicity. A betulin-derived conjugate displayed a Ki value of 0.129 μM and an EC50 value of 8.5 μM for human A375 melanoma cells.
Article
Chemistry, Medicinal
Najeeb Ur Rehman, Saeed Ullah, Tanveer Alam, Sobia Ahsan Halim, Tapan Kumar Mohanta, Ajmal Khan, Muhammad U. Anwar, Rene Csuk, Satya Kumar Avula, Ahmed Al-Harrasi
Summary: A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-beta-boswellic acid and 11-keto-beta-boswellic acid were synthesized using click chemistry. These compounds exhibited potent α-glucosidase inhibitory activity and showed interactions with amino acids in the active site.
Article
Chemistry, Multidisciplinary
Niels Heise, Julia Heisig, Linda Ho Hoehlich, Sophie Hoenke, Rene Csuk
Summary: 36 substituted benzylamides were synthesized from maslinic acid, bredemolic acid, and augustic acid, and their cytotoxicity was evaluated in various human tumor cell lines and non-malignant fibroblasts. The benzylamides derived from maslinic acid exhibited higher cytotoxicity compared to those derived from augustic acid or bredemolic acid. The most effective compound (compound 18, derived from maslinic acid) showed an EC50 value of 1.3 μM against A375 melanoma cells. Further staining experiments revealed that this compound primarily induced apoptosis rather than necrosis.
RESULTS IN CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Marie Kozubek, Toni C. Denner, Marc Eckert, Sophie Hoenke, Rene Csuk
Summary: Maslinic acid was converted to rhodamine conjugates with different alkyl moieties, which showed high cytotoxicity, especially for A2780 cells. Among them, a propyl substituted rhodamine conjugate exhibited low EC50 values of EC50 = 0.01 μM and was approximately 15 times more cytotoxic to cancer cells than non-malignant fibroblasts (NIH 3 T3). The cytotoxicity was correlated with the lipophilicity of the residues, suggesting an interaction of the conjugates with the inner mitochondrial membrane as they acted as mitocanes.
RESULTS IN CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anastasiya V. Petrova, Oxana B. Kazakova, Ivan S. Nazarov, Rene Csuk, Niels V. Heise
Summary: A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing various functional groups have been synthesized and evaluated for their acetylcholinesterase inhibitory activities. The results showed that the bromo- and azido-derivatives of 28-oxo-allobetuline and betulinic acid exhibited the most potent inhibitory activity against AChE. Further experiments demonstrated the cyano-derivatives of betulinic acid as mixed-type inhibitors with low Ki values.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Chemistry, Medicinal
Oliver Kraft, Anne-Kathrin Hartmann, Sarah Brandt, Sophie Hoenke, Niels V. Heise, Rene Csuk, Thomas Mueller
Summary: Amides and rhodamine B conjugates of pentacyclic triterpene acids have demonstrated excellent cytotoxicity against human tumor cells. The spacer attached to the carboxyl group at ring E determines the cytotoxicity of these conjugates. One acetylated homopiperazinyl spacered rhodamine B conjugate showed high cytotoxicity against ovarian carcinoma cells. These conjugates act as mitocans and induce apoptosis, and have the ability to overcome resistance to standard chemotherapeutic drugs, making them promising candidates for chemotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Shengxin Sun, Xia Wang, Renei Csuk, Shengkun Li
Summary: Drimane meroterpenoids have attracted attention for their structural diversity and bioactivity, but the lack of an efficient synthetic route has hindered further development. A nickel-catalyzed decarboxylative cross-coupling method has been established to access a variety of drimane meroterpenoids, featuring mild conditions and tolerance for challenging functional groups. This method enables the scalable synthesis of advanced intermediates for late-stage functionalizations, which has led to the discovery of new antifungal leads against Rhizoctonia solani.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Niels Heise, Florian Lehmann, Rene Csuk, Thomas Mueller
Summary: This study focuses on the development of triterpenoic acid-rhodamine conjugates with fluorescence shifted to the near-infrared (NIR) region for theranostic applications in cancer research. Spectral analysis revealed emission wavelengths around λ = 760 nm, enabling stronger signals and deeper tissue penetration. The conjugates were evaluated using SRB assays on tumor cell lines and non-malignant fibroblasts, demonstrating low nanomolar activity and high selectivity, similarly to their known rhodamine B counterparts. Additional staining experiments proved their mode of action as mitocans.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Chen Yang, Shengxin Sun, Wei Li, Yushuai Mao, Qiao Wang, Yabing Duan, Renei Csuk, Shengkun Li
Summary: A novel antifungal scaffold, isoquinoline-3-hydrazides, was identified through a bioassay-guided scaffold subtraction. The compound LW3 showed a broad-spectrum antifungal activity and no cross-resistance to commonly used fungicides. This finding highlights the practical potential of isoquinoline hydrazides as a novel model in fungicide innovation.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Niels V. Heise, Toni C. Denner, Selina Becker, Sophie Hoenke, Rene Csuk
Summary: In this study, Asiatic acid was converted into different types of rhodamine conjugates with piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacers. The compounds were tested for cytotoxic activity, and compound 12 showed the highest cytotoxicity with an EC50 of 0.8 nM. However, compound 18, with a ring expanded 1,5-diazocinyl moiety and n-propyl substituents, exhibited the highest selectivity with a selectivity factor of almost 190 while maintaining high cytotoxicity (EC50 = 1.9 nM for A2780 ovarian carcinoma).
Article
Chemistry, Medicinal
Sophie Hoenke, Benjamin Brandes, Rene Csuk
Summary: A non-cytotoxic aza-BODIPY derivative was designed and synthesized in a few simple steps. It was conjugated to 3-O-acetyl-triterpene carboxylic acids and the resulting conjugates exhibited selective targeting of the endoplasmic reticulum.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY REPORTS
(2023)
Article
Chemistry, Medicinal
Niels V. Heise, Sophie Hoenke, Immo Serbian, Rene Csuk
Summary: Ursolic acid was used for the synthesis of corosolic acid, and the synthesized compounds showed significant cytotoxicity against human tumor cells with high selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY REPORTS
(2022)
