Article
Cell Biology
Sachin Verma, David Crawford, Ali Khateb, Yongmei Feng, Eduard Sergienko, Gaurav Pathria, Chen-Ting Ma, Steven H. Olson, David Scott, Rabi Murad, Eytan Ruppin, Michael Jackson, Ze'ev A. Ronai
Summary: This study demonstrates the dependence of melanoma on the mitochondrial protein GCDH for cell survival and tumor growth. Inhibiting the GCDH pathway through NRF2 glutarylation leads to cell death and suppression of melanoma growth.
NATURE CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
James A. Roberts, Richard D. Rainbow, Parveen Sharma
Summary: Cardiovascular toxicity and diseases have a detrimental impact on morbidity and mortality. The dysregulation of the NRF2 transcription factor can lead to susceptibility to toxicity and subsequent tissue dysfunction in the cardiovascular system. Stimulation of the NRF2 signalling pathway has shown potential in alleviating cardiotoxicity and cardiovascular disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Varisha Khan, Shahid Umar, Noushina Iqbal
Summary: The severity of salt stress poses a significant threat to crop growth and food security. Current strategies to reduce stress are not always environmentally friendly or sustainable. In this study, the researchers investigated the use of plant-growth-promoting rhizobacteria (PGPR) as a sustainable stress reduction strategy. They found that the application of Pseudomonas fluorescens individually was effective in reducing stress and improving plant growth and photosynthesis, but the greatest alleviation was observed with the combined application of Pseudomonas fluorescens and Azotobacter chroococcum. The combined application resulted in decreased oxidative stress, increased osmolyte content, and enhanced antioxidative enzyme activity, leading to improved cell viability and reduced damages to the leaves. Based on these results, supplementing plants with PGPR in combination can mitigate the negative impacts of salt stress and increase plant yield.
Review
Biochemistry & Molecular Biology
Ignacio Moratilla-Rivera, Marta Sanchez, Jose Antonio Valdes-Gonzalez, Maria Pilar Gomez-Serranillos
Summary: Neurodegenerative diseases (NDs) are common diseases affecting the West due to increased life expectancy. Cells accumulate oxidative damage, triggering neurodegeneration. The transcription factor Nrf2 regulates endogenous antioxidant systems and induces the transcription of genes containing ARE in response to prooxidant conditions. Natural products such as quercetin, curcumin, and terpenoids can positively modulate Nrf2, reducing oxidative damage to the nervous system. This review aims to update knowledge on the potential treatments for NDs by activating the Nrf2 pathway with secondary metabolites of health interest.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tibor Maliar, Maria Maliarova, Marcela Blazkova, Marek Kunstek, L'ubica Uvackova, Jana Viskupicova, Andrea Purdesova, Patrik Benovic
Summary: Oxidative stress, caused by physiological and nonphysiological factors, is defined by the balance between antioxidants and pro-oxidants. This paper presents a methodology for assessing both antioxidant and pro-oxidant activity and reveals preliminary findings on the correlation between certain compounds and plant extracts.
Article
Biochemistry & Molecular Biology
Jesus Herrera-Bravo, Jorge F. Beltran, Nolberto Huard, Kathleen Saavedra, Nicolas Saavedra, Marysol Alvear, Fernando Lanas, Luis A. Salazar
Summary: This study found that Pinot noir pomace extract contains malvidin-3-glucoside, a predominant anthocyanin. Anthocyanins can modify the interaction between Keap1 and Nrf2, without promoting Nrf2 transcription. In addition, the extract can regulate the expression of HO-1 and NQO1 genes, thus protecting cells against oxidative stress.
Review
Cell Biology
Javad Sharifi-Rad, Veronique Seidel, Michalak Izabela, Margalida Monserrat-Mequida, Antoni Sureda, Valeska Ormazabal, Felipe A. Zuniga, Shivaprasad Shetty Mangalpady, Raffaele Pezzani, Alibek Ydyrys, Gulmira Tussupbekova, Miquel Martorell, Daniela Calina, William C. Cho
Summary: Cancer is a leading cause of death worldwide, and its development is linked to oxidative stress. The transcription factor Nrf2 plays a vital role in protecting cells against oxidative stress in cancer growth, progression, and therapy resistance. Therefore, innovative inhibitors targeting Nrf2 are being investigated. This comprehensive review explores the potential of phenolic compounds, found in traditional plant-based remedies, as effective anticancer agents by inhibiting Nrf2. The clinical applications of naturally-occurring bioactive compounds as Nrf2 inhibitors, specifically polyphenols, are also discussed.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Fangfang Li, Jingfeng Peng, Hui Feng, Yiming Yang, Jianbo Gao, Chunrui Liu, Jie Xu, Yanru Zhao, Siyu Pan, Yixiao Wang, Luhong Xu, Wenhao Qian, Jing Zong
Summary: This study reveals that KLF9 exacerbates cardiac dysfunction, inflammatory response, and oxidative stress in diabetic cardiomyopathy. KLF9 may be a potential therapeutic target for diabetic cardiomyopathy.
Article
Immunology
Johirul Islam, Alpa Shree, Abul Vafa, Shekh M. Afzal, Sarwat Sultana
Summary: The study highlights the protective effect of Taxifolin on Benzo[a]pyrene-induced lung injury in mice, showing that Taxifolin suppresses oxidative stress and inflammation through stimulating the Nrf2 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Ya Zhang, Qifang Wu, Jian Liu, Zhongshan Zhang, Xiaojing Ma, Yaoyue Zhang, Jiawen Zhu, Ronald W. Thring, Mingjiang Wu, Yitian Gao, Haibin Tong
Summary: Sulforaphane extracted from high-risk diet can improve insulin resistance by increasing glucose uptake and insulin signaling.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Shujian Wu, Xiyu Liao, Zhenjun Zhu, Rui Huang, Mengfei Chen, Aohuan Huang, Jumei Zhang, Qingping Wu, Juan Wang, Yu Ding
Summary: Oxidative stress (OS) is caused by an imbalance between reactive oxygen species and antioxidant levels, leading to inflammation and various diseases. Nrf2 and NF-KB play crucial roles in combating OS and regulating inflammatory responses. Recent studies show that the Nrf2 signaling pathway interacts with the NF-KB signaling pathway in OS, and natural compounds can activate these defense systems to alleviate OS and inflammation.
Article
Biochemistry & Molecular Biology
Aryatara Shakya, Pengfei Liu, Jack Godek, Nicholas W. Mckee, Matthew Dodson, Annadurai Anandhan, Aikseng Ooi, Joe G. N. Garcia, Max Costa, Eli Chapman, Donna D. Zhang
Summary: The study found that p97 is a ubiquitin-targeted ATP-dependent segregase that regulates proteostasis, in addition to other cellular functions. It negatively regulates NRF2 by extracting ubiquitylated NRF2 from the KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex, facilitating proteasomal destruction. The study also identified p97 as an NRF2-target gene that maintains redox homeostasis through a negative feedback loop, and found a positive correlation between NRF2 activation and p97 expression in human cancer patients. Inhibition of both NRF2 and p97 could be a promising treatment strategy for cancer patients.
Review
Biochemistry & Molecular Biology
Tony Heurtaux, David S. Bouvier, Alexandre Benani, Sergio Helgueta Romero, Katrin B. M. Frauenknecht, Michel Mittelbronn, Lasse Sinkkonen
Summary: The translation mentions that the nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor that regulates hundreds of genes involved in various biological functions and diseases. It also highlights the importance of NRF2 activity stability in maintaining redox balance and brain homeostasis.
Article
Biochemistry & Molecular Biology
Kai-Na Shi, Pang -Bo Li, Hui-Xiang Su, Jing Gao, Hui-Hua Li
Summary: Oxidative stress is an important factor in cardiac injury after ischemia-reperfusion (I/R). The drug MK-886, which inhibits ALOX5, has been found to have anti-inflammatory and antioxidant effects. This study demonstrated that MK-886 treatment attenuated cardiac dysfunction, reduced infarct area, decreased myocyte apoptosis, and decreased oxidative stress in an I/R-induced heart injury model, possibly through modulation of the keap1-NRF2 pathway.
Review
Cell Biology
Yang Liu, Xiaofan Yang, Yutian Liu, Tao Jiang, Sen Ren, Jing Chen, Hewei Xiong, Meng Yuan, Wenqing Li, Hans-Gunther Machens, Zhenbing Chen
Summary: The NRF2 signaling pathway plays a crucial role in wound healing by regulating anti-inflammatory and antioxidant effects, and it has important clinical significance in this process.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
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, Medicinal
Andreia Fortuna, Rita Goncalves-Pereira, Paulo J. Costa, Radek Jorda, Veronika Vojackova, Gabriel Gonzalez, Niels Heise, Rene Csuk, M. Conceicao Oliveira, Nuno M. Xavier
Summary: This study describes the synthesis and biological evaluation of novel guanidino sugars as isonucleoside analogs. Some of the compounds showed selective inhibition of acetylcholinesterase and moderate antiproliferative effects in chronic myeloid leukemia and breast cancer cells. The most potent compound also exhibited low toxicity in human fibroblasts.
Article
Biochemistry & Molecular Biology
Oliver Kraft, Ann-Kathrin Hartmann, Sophie Hoenke, Immo Serbian, Rene Csuk
Summary: Triterpenoids, such as gypsogenin, hederagenin, and madecassic acid derivatives, show great potential as leading structures for developing new drugs. Our study focused on the synthesis and cytotoxic evaluation of these derivatives, and found that acetylated amides and rhodamine B conjugates exhibited increased cytotoxicity against tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
