Article
Pharmacology & Pharmacy
Hibah M. Aldawsari, Osama A. A. Ahmed, Nabil A. Alhakamy, Thikryat Neamatallah, Usama A. Fahmy, Shaimaa M. Badr-Eldin
Summary: This study aimed at formulating and optimizing RLX emulsomes (RLX-EMLs) to enhance the drug's antitumor activity. The optimized formulation exhibited good vesicle size, zeta potential, drug entrapment, and release efficiency, resulting in significant anticancer effects on MCF-7 cells. By modulating apoptotic pathways, RLX-EMLs demonstrated enhanced cytotoxicity on tumor cells.
Article
Chemistry, Medicinal
Xiangping Deng, Xiaofei Deng, Wentao Ning, Lilan Xin, Qiuzi Li, Zhiye Hu, Baohua Xie, Kaiwei Liang, Chang Min, Chune Dong, Jian Huang, Hai-Bing Zhou
Summary: Novel dual-functional ER & alpha; degraders were developed, which exhibited potent antiproliferative and ER & alpha; degradation activity, providing guidance for developing new antitumor drug candidates for ER & alpha;(+) breast cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Polymer Science
Ahmed Al Saqr, Shahid Ud Din Wani, H. V. Gangadharappa, Mohammed F. Aldawsari, El-Sayed Khafagy, Amr S. Abu Lila
Summary: Despite the challenges in breast cancer therapy, the study successfully developed docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) with improved anticancer activity against breast cancer cell lines. The DXL-loaded SF-NPs showed enhanced cytotoxic potential and cellular uptake compared to free DXL, suggesting the potential of silk fibroin nanoparticles as a promising delivery vehicle for breast cancer treatment.
Article
Biochemistry & Molecular Biology
Boryana Nikolova-Mladenova, Georgi Momekov, Zvetanka Zhivkova, Irini Doytchinova
Summary: Despite advancements in anticancer therapy, finding new and efficient anticancer agents remains a priority. Based on the structure-activity relationships of salicylaldehyde hydrazones, three novel derivatives were designed. These compounds showed appropriate drug likeness and significant anticancer activity, particularly in leukemic and breast cancer cell lines, with remarkable selectivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Iga K. Mieczkowska, Garyfallia Pantelaiou-Prokaki, Evangelos Prokakis, Geske E. Schmidt, Lukas C. Muller-Kirschbaum, Marcel Werner, Madhobi Sen, Taras Velychko, Katharina Jannasch, Christian Dullin, Joanna Napp, Klaus Pantel, Harriet Wikman, Maria Wiese, Christof M. Kramm, Frauke Alves, Florian Wegwitz
Summary: Breast cancer is the most common cancer in women and rarely occurs in men. The basal-like BC subtype lacks drug targets and is resistant to cytotoxic therapies. Loss of PRC2 activity leads to upregulation of the NFATc1 gene, promoting aggressiveness and therapy resistance in breast cancer cells.
CELL DEATH & DISEASE
(2021)
Article
Nutrition & Dietetics
Marek Szwiec, Wojciech Marciniak, Roza Derkacz, Tomasz Huzarski, Jacek Gronwald, Cezary Cybulski, Tadeusz Debniak, Anna Jakubowska, Marcin Lener, Michal Falco, Jozef Kladny, Piotr Baszuk, Jerzy Duszynski, Joanne Kotsopoulos, Steven A. Narod, Jan Lubinski
Summary: A recent prospective study found an association between low serum selenium level and five- and ten-year survival rates among breast cancer patients. Further research is needed to confirm the protective effect of selenium on breast cancer survival, and potential investigation into selenium supplementation for patients.
Article
Biochemistry & Molecular Biology
Elena G. Varlamova, Mikhail Goltyaev, Valentina N. Mal'tseva, Egor A. Turovsky, Ruslan M. Sarimov, Alexander Simakin, Sergey Gudkov
Summary: Selenium nanoparticles (SeNP) have gained popularity for their high biocompatibility, stability, and selectivity, with numerous studies proving their anticarcinogenic effects. This study investigated the molecular mechanisms regulating SeNP-induced cytotoxic effects on four human cancer cell lines, highlighting varied concentration-dependent outcomes and the induction of apoptosis through different signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Arindam Bandyopadhyay, Saraswati Garai, Prajna Paramita Banerjee, Shelley Bhattacharya, Ansuman Chattopadhyay
Summary: The study isolated four different types of dammarane saponins from Bacopa monniera and found them to have toxic effects on human breast cancer cell lines, leading to apoptosis. These saponins showed high efficacy and relatively low toxicity in cancer cells, suggesting they may be an effective alternative for breast cancer therapeutics.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Sang-Cheol Lee, Na-Hyun Lee, Kapil D. Patel, Soo-Kyung Jun, Jeong-Hui Park, Jonathan Campbell Knowles, Hae-Won Kim, Hae-Hyoung Lee, Jung-Hwan Lee
Summary: In this study, nano-sized antioxidative biomaterials using selenium were developed to protect and accelerate the differentiation of C2C12 myoblasts in an oxidative stress environment. The selenium nanoparticles showed antioxidant effects, reduced apoptosis and intracellular ROS levels, and up-regulated genes associated with myoblast differentiation. These results suggest that SeNPs can be used for the treatment of skeletal muscle in a cellular redox environment.
Article
Biochemistry & Molecular Biology
Ayse Mine Yilmaz Goler, Ayse Tarbin Jannuzzi, Abanish Biswas, Subodh Mondal, Vinay N. Basavanakatti, Raghusrinivasan Jayaprakash Venkatesan, Hatice Yildirim, Mahmut Yildiz, Huelya Celik Onar, Niluefer Bayrak, Venkatesan Jayaprakash, Amac Fatih TuYuN
Summary: Finding bioactive molecules in the vast chemical universe is challenging. Quinone moiety has unique biological properties, especially in cancer treatment. In this study, five quinolinequinones were submitted to the NCI for antiproliferative screening, and four of them showed promising effects against different types of cancer. Further investigations were conducted on the mode of action, cytotoxic activities, and pharmacokinetic profiles of the most promising compounds AQQ2 and AQQ3. AQQ2 exhibited anticancer activity through apoptosis induction and cell cycle alterations.
CHEMISTRY & BIODIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Kamil Demircan, Qian Sun, Ylva Bengtsson, Petra Seemann, Johan Vallon-Christersson, Martin Malmberg, Lao H. Saal, Lisa Ryd, Waldemar B. Minich, Ake Borg, Jonas Manjer, Lutz Schomburg
Summary: The presence of SELENOP autoantibodies in breast cancer patients is associated with poor prognosis, particularly in patients with low selenium levels. These autoantibodies may disrupt the transport function of SELENOP, leading to an increased risk of recurrence and mortality.
Article
Plant Sciences
Francis Adu-Amankwaah, Kudzanai Ian Tapfuma, Raeesa Hoosen Hussan, Ndivhuwo Tshililo, Lucinda Baatjies, Maano Valerie Masiphephethu, Lawrence Mabasa, Vuyo Mavumengwana
Summary: Breast cancer is a leading cause of cancer-related deaths in women globally. This study investigated the potential use of nine Fynbos plants in treating breast cancer and found that E. racemosa and S. africana-lutea are promising candidates for further development of therapeutic agents.
SOUTH AFRICAN JOURNAL OF BOTANY
(2022)
Article
Cell Biology
Denisse A. Gutierrez, Lisett Contreras, Paulina J. Villanueva, Edgar A. Borrego, Karla Moran-Santibanez, Jessica D. Hess, Rebecca DeJesus, Manuel Larragoity, Ana P. Betancourt, Jonathon E. Mohl, Elisa Robles-Escajeda, Khodeza Begum, Sourav Roy, Robert A. Kirken, Armando Varela-Ramirez, Renato J. Aguilera
Summary: In this study, a novel pyrazole-based derivative (P3C) was found to exhibit strong cytotoxicity against various human cancer cell lines, especially triple-negative breast cancer cells. The mechanism of cytotoxicity involves the accumulation of reactive oxygen species (ROS), mitochondrial depolarization, and activation of apoptotic pathways.
Article
Engineering, Chemical
Mahshid Mohammadi, Vasudeo Zambare, Zacharias Suntres, Lew Christopher
Summary: Lichens produce a wide range of secondary metabolites, and there is increasing interest in using these bioactive molecules for drug discovery. In this study, gyrophoric acid (GA) was isolated from the lichen Umbilicaria muhlenbergii and identified using various analytical techniques. GA showed strong cytotoxic properties against breast cancer cells, indicating its potential as an anticancer drug.
Article
Oncology
Sanaa K. Bardaweel, Lina A. Dahabiyeh, Bushra M. Akileh, Dana D. Shalabi, Afnan K. AlHiary, Judy Pawling, James W. Dennis, Anas M. Abdel Rahman
Summary: The study found that the COX-2 inhibitor celecoxib demonstrated significant antiproliferative activity against all tested breast cancer cell lines, and exhibited a synergistic effect when combined with the selective estrogen receptor modulator raloxifene. Celecoxib treatment increased cell apoptosis and substantially inhibited cancer cell migration.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Ilona Domracheva, Iveta Kanepe-Lapsa, Reinis Vilskersts, Imanta Bruvere, Egils Bisenieks, Astrida Velena, Baiba Turovska, Gunars Duburs
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2020)
Article
Chemistry, Organic
Pavel Arsenyan, Jelena Vasiljeva, Ilona Domracheva, Iveta Kanepe-Lapsa
CHEMISTRY OF HETEROCYCLIC COMPOUNDS
(2020)
Article
Biochemistry & Molecular Biology
Nadide Altincekic, Sophie Marianne Korn, Nusrat Shahin Qureshi, Marie Dujardin, Marti Ninot-Pedrosa, Rupert Abele, Marie Jose Abi Saad, Caterina Alfano, Fabio C. L. Almeida, Islam Alshamleh, Gisele Cardoso de Amorim, Thomas K. Anderson, Cristiane D. Anobom, Chelsea Anorma, Jasleen Kaur Bains, Adriaan Bax, Martin Blackledge, Julius Blechar, Anja Bockmann, Louis Brigandat, Anna Bula, Matthias Buetikofer, Aldo R. Camacho-Zarco, Teresa Carlomagno, Icaro Putinhon Caruso, Betul Ceylan, Apirat Chaikuad, Feixia Chu, Laura Cole, Marquise G. Crosby, Vanessa de Jesus, Karthikeyan Dhamotharan, Isabella C. Felli, Jan Ferner, Yanick Fleischmann, Marie-Laure Fogeron, Nikolaos K. Fourkiotis, Christin Fuks, Boris Fuertig, Angelo Gallo, Santosh L. Gande, Juan Atilio Gerez, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Serafima Guseva, Carolin Hacker, Sabine Haefner, Bing Hao, Bruno Hargittay, K. Henzler-Wildman, Jeffrey C. Hoch, Katharina F. Hohmann, Marie T. Hutchison, Kristaps Jaudzems, Katarina Jovic, Janina Kaderli, Gints Kalnins, Iveta Kanepe, Robert N. Kirchdoerfer, John Kirkpatrick, Stefan Knapp, Robin Krishnathas, Felicitas Kutz, Susanne zur Lage, Roderick Lambertz, Andras Lang, Douglas Laurents, Lauriane Lecoq, Verena Linhard, Frank Loehr, Anas Malki, Luiza Mamigonian Bessa, Rachel W. Martin, Tobias Matzel, Damien Maurin, Seth W. McNutt, Nathane Cunha Mebus-Antunes, Beat H. Meier, Nathalie Meiser, Miguel Mompean, Elisa Monaca, Roland Montserret, Laura Marino Perez, Celine Moser, Claudia Muhle-Goll, Thais Cristtina Neves-Martins, Xiamonin Ni, Brenna Norton-Baker, Roberta Pierattelli, Letizia Pontoriero, Yulia Pustovalova, Oliver Ohlenschlaeger, Julien Orts, Andrea T. Da Poian, Dennis J. Pyper, Christian Richter, Roland Riek, Chad M. Rienstra, Angus Robertson, Anderson S. Pinheiro, Raffaele Sabbatella, Nicola Salvi, Krishna Saxena, Linda Schulte, Marco Schiavina, Harald Schwalbe, Mara Silber, Marcius da Silva Almeida, Marc A. Sprague-Piercy, Georgios A. Spyroulias, Sridhar Sreeramulu, Jan-Niklas Tants, Kaspars Tars, Felix Torres, Sabrina Toews, Miguel A. Trevino, Sven Trucks, Aikaterini C. Tsika, Krisztina Varga, Ying Wang, Marco E. Weber, Julia E. Weigand, Christoph Wiedemann, Julia Wirmer-Bartoschek, Maria Alexandra Wirtz Martin, Johannes Zehnder, Martin Hengesbach, Andreas Schlundt
Summary: The international COVID19-NMR consortium aims to gather scientific expertise worldwide to provide new approaches for understanding the molecular components of SARS-CoV-2. By making viral proteins and RNAs available, the consortium accelerates research on the virus and provides protocols for large-scale production. The NMR investigations and resources disclosed through the consortium offer valuable insights and tools for further studies on SARS-CoV-2.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Analytical
Pavels Dimitrijevs, Pavel Arsenyan
Summary: Cardiolipin (CL) is a key phospholipid important for mitochondrial function and tissue integrity. A new fluorescent CL-specific probe has been developed for quantifying CL in mitochondrial fractions and assessing drug affinity for CL. CL concentration varies in different tissues, with higher levels in cancer cells and tissues with high proliferation rates.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Organic
Sindija Lapcinska, Pavels Dimitrijevs, Pavel Arsenyan
Summary: A mild and efficient method for the preparation of 3-sulfenyl and 3-selenyl coumarins and quinolinones using artificial light or sunlight as a mediator is presented. The method utilizes nonyl acridine orange as a photocatalyst to generate sulfenyl radicals from thiols, which are then trapped by heterocycles. The protocol has a broad scope and can be applied to various thiols, including short cysteine-containing peptides, showing high tolerance for amino acids with sensitive groups.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Edgars Paegle, Pavel Arsenyan
Summary: The simplest preparation method for benzo[b]tellurophenes has been developed. The cyclization of o-haloarylalkynes in the presence of Te-NaOH-DMSO occurs by simple mixing and heating, providing the corresponding benzo[b]tellurophenes in high yields. The catalytic telluration of aryl iodide substrates expands the applicability of this cyclization cascade approach.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Olga Bobileva, Raitis Bobrovs, Evelina Elva Sirma, Iveta Kanepe, Anna L. Bula, Liene Patetko, Anna Ramata-Stunda, Solveiga Grinberga, Aigars Jirgensons, Kristaps Jaudzems
Summary: SARS-CoV-2 nsp14 guanine-N7-methyltransferase is crucial for viral RNA translation, and compound 5p was developed as a potent inhibitor targeting both SAM and mRNA-binding pockets of nsp14. It exhibited subnanomolar inhibitory activity and enhanced cell membrane permeability compared to the parent inhibitor, suggesting its potential as a bisubstrate inhibitor for further development in combating the virus.
Article
Chemistry, Medicinal
Pavels Dimitrijevs, Marina Makrecka-Kuka, Agnieszka Bogucka, Marko Hyvonen, Teodors Pantelejevs, Pavel Arsenyan
Summary: Changes in cancer metabolic pathways provide an opportunity for targeted elimination of tumor cells. The design and mechanism of action of a novel class of selective PKM2 inhibitors as anti-cancer agents are reported. Compound 5c is the most active with IC50 = 0.35 +/- 0.07 μM, downregulating PKM2 mRNA expression and inducing oxidative burst, making it cytotoxic for various cancer types. Isoselenazolium chlorides inhibit PKM2 by inducing a functionally deficient tetrameric assembly and displaying a competitive inhibitor character. The discovery of robust PKM2 inhibitors is not only valuable for anticancer therapy, but also crucial for studying the role of PKM2 in cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Edgars Paegle, Pavels Dimitrijevs, Pavel Arsenyan
Summary: Targeted therapy is an important approach to fight against cancer. In this study, 7 novel benzoselenophenes were designed and synthesized for their estrogen receptor alpha (ER-a) binding activity and cytotoxicity. The results showed that compound 21b exhibited higher ER-a binding affinity than the widely used SERM drug raloxifene, and it was also non-toxic in rat cardiomyoblasts, suggesting the potential of substituted benzo[b]selenophene as a scaffold for developing ER-a modulators and downregulators for the treatment of estrogen receptor positive cancers.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Materials Science, Multidisciplinary
Karolis Leitonas, Brigita Vigante, Dmytro Volyniuk, Audrius Bucinskas, Rasa Keruckiene, Pavels Dimitrijevs, Tien-Lung Chiu, Juozas Vidas Grazulevicius, Pavel Arsenyan
Summary: Proposing 3,5-dicyanopyridine motifs for the design of electroactive materials for optoelectronic devices, three electron-transporting semiconductors are synthesised. The compounds have high triplet energies, high glass-transition temperatures, ionisation potentials, and electron affinities. Two compounds exhibit deep-blue emissions arising from hybridised local and charge-transfer states, while another compound with an additional carbazole donor unit shows pure charge-transfer emission. The different hosting properties of the compounds result in varying efficiencies of thermally activated delayed fluorescence of the emitter DAcIPN. An organic light-emitting diode based on the newly synthesised host demonstrates a significantly higher external quantum efficiency compared to a device based on the conventional host. Time-resolved electroluminescence study confirms efficient emissive harvesting of triplets with the 3,5-dicyanopyridine-based host.
JOURNAL OF MATERIALS CHEMISTRY C
(2023)
Article
Chemistry, Multidisciplinary
Jelena Vasiljeva, Marina Makrecka-Kuka, Ilona Domracheva, Karlis Vilks, Pavels Dimitrijevs, Pavel Arsenyan
Summary: This study reports the design and synthesis of novel selenophenoquinolinones and their ability to reverse doxorubicin resistance in uterus sarcoma cells. Compound 5e demonstrated the best cytotoxicity and attenuated cell resistance to doxorubicin by inhibiting ABCB1 transporter activity and suppressing ABCB1 gene expression.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Sindija Lapcinska, Andrea Revilla-Cuesta, Irene Abajo-Cuadrado, Jose Cuevas, Manuel Avella, Pavel Arsenyan, Tomas Torroba
Summary: The portable testing setup described in the concept allows for real-time detection of TATP vapor traces, with controlled trapping of the analyte through gas sample recirculation for reliable results at very low concentrations in air.
MATERIALS CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Sindija Lapcinska, Pavel Arsenyan
Summary: Efficient methods have been developed for the construction of nitrogen and oxygen containing heterocyclic systems attached to selenocysteine or selenoglutathione. Inorganic oxidants or a mild Lewis acid were used to generate selanyl electrophiles which were further reacted to form different compounds via 6-endo-dig cyclization. The use of visible light led to divergent reactivity, resulting in triple bond addition products or spirocyclic compounds with selenocysteine moieties.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Pavel Arsenyan, Alla Petrenko, Sergey Belyakov
Summary: The study introduces a synthesis method for N-polyaromatic compounds with multiple fused aromatic rings, demonstrating the construction of these compounds in a simple one-pot process with excellent yields under mild reaction conditions.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Materials Science, Multidisciplinary
Pavel Arsenyan, Brigita Vigante, Karolis Leitonas, Dmytro Volyniuk, Viktorija Andruleviciene, Levani Skhirtladze, Sergey Belyakov, Juozas Vidas Grazulevicius
Summary: A method for post-functionalization of dicyanopyridines using 3,6-di-tert-butyl-carbazole or 3,7-dibromophenothiazine was developed, leading to green and orange thermally activated delayed fluorescence (TADF) with close emission quantum yields. Organic light-emitting diodes were developed using the synthesized compounds, showing different efficiencies and lifetimes based on the type of TADF emitter used. The dual-TADF emitters exhibited ultra-long fluorescence lifetimes, resulting in decreased stability and efficiency of the electronic device.
JOURNAL OF MATERIALS CHEMISTRY C
(2021)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
