Article
Chemistry, Multidisciplinary
Sk Abdul Amin, Prakruti Trivedi, Nilanjan Adhikari, Ganesh Routholla, Dhanya Vijayasarathi, Sanjib Das, Balaram Ghosh, Tarun Jha
Summary: The study focused on designing pentanoic acid based hydroxamates as selective HDAC8 inhibitors, with compounds 7i and 7f identified as selective inhibitors that showed better antiproliferative activities against certain cancer cell lines and induced significant cell growth arrest in the G2/M phase. These findings suggest that these compounds could serve as lead molecules for further investigation into their anticancer potentials.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yawen Yang, Qingqing Liu, Xinyi Wang, Shaohua Gou
Summary: A series of novel histone deacetylase (HDAC) inhibitors derived from 3-(benzazol-2-yl)quinoxaline derivatives were designed and synthesized using a pharmacophore fusion strategy. In vitro studies demonstrated that most of the synthesized compounds exhibited significant anti-proliferative activity. Among them, compound 10c showed the highest cytotoxicity in HCT-116 cells with an IC50 value of 0.91 μM, surpassing Vorinostat (5.66 μM). Further investigation revealed that compound 10c up-regulated the acetylation levels of H3 and alpha-tubulin, inhibited Topo I, and induced the release of apoptotic biomarkers, highlighting its potential as a promising anti-cancer HDAC inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Physical
Negar Omidkhah, Farzin Hadizadeh, Khalil Abnous, Razieh Ghodsi
Summary: A series of quinoline-based benzamide derivatives were designed and synthesized as HDAC inhibitors and anticancer agents. The synthesized compounds showed cytotoxic activity against several human cancer cell lines, with the highest cytotoxicity observed in colorectal cancer and lung cancer cells. Compounds with a methyl group at position 2 of the quinoline ring exhibited better cytotoxicity compared to those with an aryl group. The most potent cytotoxic compounds also displayed strong enzyme inhibitory activity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Immunology
Melanie A. Whitmore, Hong Li, Wentao Lyu, Sharmily Khanam, Guolong Zhang
Summary: The combination of HDACi and DNMTi/HMTi showed a strong synergy in inducing HDP gene expression, and also regulated the expression of tight junction proteins.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Conrad V. Simoben, Ehab Ghazy, Patrik Zeyen, Salma Darwish, Matthias Schmidt, Christophe Romier, Dina Robaa, Wolfgang Sippl
Summary: Histone-modifying proteins are potential targets for treating diseases, and in silico methods are used in drug discovery programs to identify lead compounds. This study investigated the binding modes of benzhydroxamates derivatives as inhibitors of Schistosoma mansoni histone deacetylase, and developed quantitative structure-activity relationship models to predict activity, which showed good correlation with experimental results.
Editorial Material
Microbiology
Tom Boissavy, Dante Rotili, Thomas Mouveaux, Emmanuel Roger, El Moukthar Aliouat, Christine Pierrot, Sergio Valente, Antonello Mai, Mathieu Gissot
Summary: Toxoplasmosis is a significant health issue for immune-deficient individuals and newborns of infected mothers. New compounds with potent anti-parasitic activity have been discovered, which can serve as therapeutic targets for the treatment of toxoplasmosis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Xiaopeng Peng, Jingxuan Chen, Ling Li, Zhiqiang Sun, Jin Liu, Yichang Ren, Junli Huang, Jianjun Chen
Summary: The novel dual HDAC3/tubulin inhibitor compound 15c showed high potency and selectivity, with excellent antiproliferative effects against various cancer cell lines and significant in vivo antitumor efficacy in a melanoma tumor model. In addition, 15c demonstrated low cardiotoxicity and no nephro-/hepatotoxicity, making it a promising potential anticancer agent.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Meran Keshawa Ediriweera
Summary: Histone acetylation is a crucial epigenetic event and continues to be an area of great interest in biochemical research. The balance between histone acetyltransferases (HATs) and histone deacetylases (HDACs) is disrupted in various human cancers. Histone deacetylase inhibitors (HDACi) have shown promising results in restoring dysregulated histone acetylation profiles and are considered as potential anti-cancer therapeutics. Recent studies have identified odd-chain fatty acids as novel HDACi, further expanding the understanding of fatty acids in cancer therapy.
DRUG DISCOVERY TODAY
(2023)
Article
Cell Biology
Sheng-Mao Wu, Yee-Jee Jan, Shih-Chuan Tsai, Hung-Chuan Pan, Chin-Chang Shen, Cheng-Ning Yang, Shu-Hua Lee, Shing-Hwa Liu, Li-Wei Shen, Chien-Shan Chiu, Jack L. Arbiser, Menghsiao Meng, Meei-Ling Sheu
Summary: This study found that Honokiol can prevent the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression. The results suggest that Honokiol inhibits HDAC3 activity by suppressing the activation of the NF-Bp65/CEBPβ signaling pathway, thereby inhibiting the migration and invasion of cancer cells. In addition, Honokiol increases the expression of ER stress markers, inhibits the expression of EMT-associated epithelial markers, and decreases Wnt/β-catenin activity, thereby blocking the metastasis of gastric cancer.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Chemistry, Physical
Yogesh Mahadu Khetmalis, Bakhya Shree, Boddupalli Venkata Siva Kumar, Markus Schweipert, Cecile Debarnot, Fathima Ashna, Murugesan Sankaranarayanan, Jamma Trinath, Vivek Sharma, Franz -Josef Meyer-Almes, Kondapalli Venkata Gowri Chandra Sekhar
Summary: A series of novel tetrahydroisoquinoline (THIQ) compounds were synthesized and evaluated as selective inhibitors of histone deacetylase 6 (HDAC 6). The compounds demonstrated potent antiproliferative activities and inhibited the colony formation in cancer cells. B10 and B24 showed the highest selectivity towards HDAC 6 with IC50 values of 0.3 μM and 0.4 μM respectively. The inhibition of cancer cell proliferation by B21 and B24 was attributed to cell cycle arrest in G1 phase and apoptotic death of the cancer cells.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Physical
Avineesh Singh, Vijay K. Patel, Harish Rajak
Summary: Pyrrole as a connecting unit demonstrates potent anticancer activity against various cancer cell lines. Substitution with different groups influences the activity of the compounds, and further development of novel SAHA analogs with promising anticancer activity can be pursued based on these studies.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Medicinal
Marcel K. W. Mackwitz, Eva Hesping, Korina Eribez, Andrea Schoeler, Yevgeniya Antonova-Koch, Jana Held, Elizabeth A. Winzeler, Katherine T. Andrews, Finn K. Hansen
Summary: This study reports on a new peptoid-based HDAC inhibitor with dual-stage antiplasmodial activity, showing potential activity against malaria parasites and selectivity for human cells. These data provide a foundation for future improvements to these dual-stage inhibitors as potential drug leads for malaria.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Lukas von Bredow, Thomas Martin Schafer, Julian Hogenkamp, Maik Tretbar, Daniel Stopper, Fabian B. Kraft, Julian Schliehe-Diecks, Andrea Scholer, Arndt Borkhardt, Sanil Bhatia, Jana Held, Finn K. Hansen
Summary: This study presents the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin-HDACi hybrid molecules. The hybrid molecules showed potent activity against P. falciparum parasites and leukemia cell lines, indicating their potential as antimalarial and antileukemia drug leads.
Review
Oncology
Robert Jenke, Nina Ressing, Finn K. Hansen, Achim Aigner, Thomas Buch
Summary: Epigenetic changes can drive cancer malignancy, while histone deacetylase inhibitors (HDACis) hold promise as anticancer drugs due to their ability to target multiple pathways relevant to the disease.
Article
Biochemistry & Molecular Biology
Sarah E. Anderson, James E. Longbotham, Patrick T. O'Kane, Fatima S. Ugur, Danica Galonic Fujimori, Milan Mrksich
Summary: By using a new assay, the study explored the binding preferences of the PHD1 domain of histone demethylase KDMSA for H3 ligands, revealing tolerance for H3Q5 mutations and a high-affinity interaction with Q5-serotonylated H3. This work demonstrates the value of PI-SAMDI and fluorescence polarization in investigating protein-ligand binding.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Kevin J. Metcalf, Blaise R. Kimmel, Daniel J. Sykora, Justin A. Modica, Kelly A. Parker, Eric Berens, Raymond Dai, Vinayak P. Dravid, Zena Werb, Milan Mrksich
Summary: This study presents a method to synthetically tune protein conjugates for improved cancer therapy. By utilizing a megamolecule approach, the researchers were able to increase cytotoxicity effects on cancer cells by modifying the domain stoichiometry of the conjugates. The results demonstrate that synthetic control of protein domain stoichiometry can enhance the structure-function relationships of protein conjugate therapeutics for cancer treatment.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Oncology
Yufan F. Wu, Lawrie Skinner, Jonathan Lewis, Michael S. Khodadoust, Youn H. Kim, Bernice Y. Kwong, Wen-Kai Weng, Richard T. Hoppe, Quaovi Sodji, Caressa Hui, Noah Kastelowitz, Sebastian Fernandez-Pol, Susan M. Hiniker
Summary: We report a case of widespread PCGD-TCL involving the bilateral arms and legs, in which the patient received radiotherapy prior to stem cell transplant. The patient showed progression in the liver, lung, and skin, followed by remarkable regression of all lesions 1.5 months later. The regression may be attributed to radiation-induced abscopal effect or immune reactivation after cessation of immunosuppressive agents.
CANCER INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Anming Yang, Huanyu Tao, Lindsey C. Szymczak, Liang Lin, Junfeng Song, Yi Wang, Silei Bai, Justin Modica, Sheng-You Huang, Milan Mrksich, Xinxin Feng
Summary: Site-specific modification of proteins using enzymatic incorporation of Dha provides a traceless ligation method and enhances peptide labeling efficiency. This approach has important applications in biological research and drug development.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Blaise R. Kimmel, Milan Mrksich
Summary: This paper introduces an enzyme building block for assembling megamolecules, which inhibits protein CRABP2 to control protein domains. By conjugating the inhibitor and a fluorescent tag to a backbone, precise control over the placement of protein domains within a single molecule is achieved.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Jennifer Grant, Blaise R. Kimmel, Lindsey C. Szymczak, Juliet Roll, Milan Mrksich
Summary: This paper presents a method that combines a microfluidic device and self-assembled monolayers to calculate the cooperativity in binding of calcium ions to PAD2. The method uses a small amount of enzyme solution and fluidic inputs, and utilizes iSAMDI to analyze the reactions. This work establishes a high-throughput and label-free approach for studying enzyme-ligand interactions and expands the applicability of microfluidics and MALDI imaging mass spectrometry.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Oncology
Quaovi H. Sodji, Jeremy P. Harris, Andrew Quon, Leslie A. Modlin, Brianna Lau, Alice Jiang, Nicholas Trakul, Peter G. Maxim, Maximilian Diehn, Billy W. Loo, Susan M. Hiniker
Summary: This study evaluated the performance of FDG-PET-CT in distinguishing between local recurrence and post-radiation changes in patients with early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy. The positive predictive value of FDG-PET-CT in identifying local recurrence was found to be relatively low, especially at early post-treatment timepoints.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Quaovi H. Sodji, Ryan Ko, Rie von Eyben, Susan G. Owen, Dante P. Capaldi, Karl Bush, Michael S. Binkley, Fahad Alrowais, Bill Pickthorn, Peter G. Maxim, Michael F. Gensheimer, Maximilian Diehn, Billy W. Loo
Summary: The purpose of this study was to evaluate the incidence of acute and late esophageal toxicity in patients with thoracic tumors treated with SABR. The results showed that 25% of patients with tumors near the esophagus developed acute esophagitis, but these toxicities were all grade 2 and temporary.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Oncology
Saravanan Nandagopal, Caiyun G. Li, Yu Xu, Quaovi H. Sodji, Edward E. Graves, Amato J. Giaccia
Summary: Many solid tumors have low levels of cytotoxic CD56(dim) natural killer (NK) cells, which is thought to contribute to the decreased response rate of immunotherapy. Complement component 3a (C3a) plays a role in immune cell trafficking into the tumor microenvironment (TME). Blocking C3a receptor (C3aR) signaling increases NK cell infiltration into the TME. Direct interaction between C3aR and the lymphocyte trafficking integrin LFA-1 decreases NK cell infiltration into the TME.
CANCER IMMUNOLOGY RESEARCH
(2022)
Review
Oncology
Bocheng Wu, Quaovi H. Sodji, Adegboyega K. Oyelere
Summary: Inflammation can be both protective and harmful. This review provides a detailed analysis of the relationships and differences between uncontrolled inflammation, fibrosis, and cancer. It highlights the challenges and opportunities in developing new therapies for these diseases, including enhancing the therapeutic benefits of current agents and exploring novel strategies. Re-evaluation of disease-specific pathways and single-cell screening technologies are also discussed as potential avenues for future drug discovery.
Article
Chemistry, Multidisciplinary
Cesar A. Patino, Prithvijit Mukherjee, Eric J. Berns, Elamar Hakim Moully, Liliana Stan, Milan Mrksich, Horacio D. Espinosa
Summary: In this study, we developed a novel live-cell analysis device that can perform membrane permeabilization and content sampling. The device interfaces with surface-based biosensors and allows for the delivery of biomolecules and multimodal analysis. Optimization of electroporation parameters enables control over the sampled contents, and the impact of cell morphology on sampling is investigated using deep-learning enhanced image analysis.
Article
Urology & Nephrology
Adeoluwa Ayoola, Quaovi H. Sodji, Sharon Chin, Periklis Panousis, Hilary P. Bagshaw, Mark K. Buyyounouski
Summary: Syndrome of inappropriate secretion of antidiuretic hormone can rarely occur after high-dose rate brachytherapy for prostate cancer, and timely diagnosis and effective management are crucial.
Article
Biochemistry & Molecular Biology
Kelly A. Parker, Stephanie Ribet, Blaise R. Kimmel, Roberto dos Reis, Milan Mrksich, Vinayak P. Dravid
Summary: Soft electron microscopy is essential for studying the characteristics of macromolecules, using low electron doses to enhance contrast. By performing scanning transmission electron microscopy in a scanning electron microscope, larger structures can be efficiently characterized with high contrast.
Article
Multidisciplinary Sciences
Che-Fan Huang, Cara J. Gottardi, Milan Mrksich
Summary: Phosphorylation plays a crucial role in cellular signaling, and dysregulation of phosphorylation can lead to diseases. However, while most studies focus on kinases, the role of phosphatases is often overlooked. This study demonstrates that basic amino acids adjacent to phosphotyrosines can restrict the activity of tyrosine phosphatases, providing insights into the mechanisms underlying disease-associated mutations and potential treatment strategies.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Quaovi H. Sodji, Dhanya K. Nambiar, Vignesh Viswanathan, Rie von Eyben, Deana Colburg, Michael S. Binkley, Caiyun G. Li, Monica M. Olcina, Daniel T. Chang, Quynh-Thu Le, Amato J. Giaccia
CANCER RESEARCH COMMUNICATIONS
(2022)
