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
Biochemistry & Molecular Biology
Jakub Ptacek, Ivan Snajdr, Jiri Schimer, Zsofia Kutil, Jana Mikesova, Petra Baranova, Barbora Havlinova, Werner Tueckmantel, Pavel Majer, Alan Kozikowski, Cyril Barinka
Summary: This article compares hydroxamate-based HDAC6-selective inhibitors commonly used in the treatment of neurological and psychiatric disorders with a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function (compound 7). In vitro screening revealed HDAC10 as a primary off-target for hydroxamate-based HDAC6 inhibitors, while compound 7 showed exquisite selectivity over all other HDAC isoforms. Cell-based assays showed lower potency for all compounds when using tubulin acetylation as a surrogate readout. Additionally, the limited selectivity of some HDAC6 inhibitors was shown to be linked to cytotoxicity in RPMI-8226 cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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, 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)
Review
Biochemistry & Molecular Biology
Anton Fruhauf, Franz-Josef Meyer-Almes
Summary: HDACs play a role in many diseases, and the hydroxamate group in HDACis may cause toxic side effects, leading to exploration of non-hydroxamic HDACis. These new inhibitors have alternative ZBGs to replace the hydroxamate group, maintaining high potency and high selectivity.
Article
Chemistry, Medicinal
Eva Hesping, Ming Jang Chua, Marc Pflieger, Yunan Qian, Lilong Dong, Prabhakar Bachu, Ligong Liu, Thomas Kurz, Gillian M. Fisher, Tina S. Skinner-Adams, Robert C. Reid, David P. Fairlie, Katherine T. Andrews, Alain-Dominique J. P. Gorse
Summary: Malaria, a deadly disease caused by Plasmodium parasites, claims a large number of lives every year. Due to the increasing resistance of the parasites to current antimalarials, there is a need for new drugs. Researchers have developed quantitative structure-activity relationship models to predict the antiplasmodial activity of hydroxamate-based HDAC inhibitors and identified three compounds with strong activity against the parasites.
ACS INFECTIOUS DISEASES
(2022)
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, 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)
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.
Review
Pharmacology & Pharmacy
Ekta Shirbhate, Ravichandran Veerasamy, Sai H. S. Boddu, Amit K. Tiwari, Harish Rajak
Summary: One significant obstacle in cancer treatment is the decrease in drug efficacy and occurrence of adverse effects. Oncolytic viruses (OVs) have gained interest as a potential method to treat cancer due to their specificity for cancerous tissue and reduced likelihood of adverse effects. Clinical trials have shown that OVs have an acceptable safety profile and are effective in treating certain types of cancer, despite their limited availability. However, further advancements are needed to enhance tumor permeation and improve virus delivery in order to make oncolytic virotherapy more effective.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Medicinal
Ruoxi Li, Dazheng Ling, Tongke Tang, Zhenghui Huang, Manjiong Wang, Yan Ding, Taiping Liu, Hanwen Wei, Wenyue Xu, Fei Mao, Jin Zhu, Xiaokang Li, Lubin Jiang, Jian Li
Summary: In this study, a total of 31 novel spirocyclic hydroxamic acid derivatives were synthesized based on the structure of the clinical anticancer drug candidate quisinostat, with compound 11 displaying broad potency against various multidrug-resistant malarial parasites both in vitro and in vivo. The compound showed specific efficacy against schizonts, acceptable metabolic stability, and pharmacokinetic properties, making it a promising PfHDAC1 inhibitor for malaria treatment and research.
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
Biochemistry & Molecular Biology
Marta Halasa, Jarogniew J. Luszczki, Magdalena Dmoszynska-Graniczka, Marzena Baran, Estera Okon, Andrzej Stepulak, Anna Wawruszak
Summary: Our study demonstrated an antagonistic effect of the cytostatic agent cisplatin (CDDP) and the histone deacetylase inhibitor cambinol (CAM) on different phenotypes of breast cancer cell lines, highlighting the importance of selecting appropriate drug combinations for effective treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
Review
Biochemistry & Molecular Biology
Long Xu, Xiaoyu Yan, Jian Wang, Yuanxin Zhao, Qingqing Liu, Jiaying Fu, Xinyi Shi, Jing Su
Summary: This article provides an overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. It discusses the roles of HDACs in the regulation of ovarian cancer metastasis and highlights the importance of developing compounds that target HDACs in the future of ovarian cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Liping Zhou, Stephanie Dodd, Christina Capacci-Daniel, Sudhakar Garad, Riccardo Panicucci, Vijay Sethuraman
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2016)
Article
Chemistry, Medicinal
Julian R. Levell, Thomas Caferro, Gregg Chenail, Ina Dix, Julia Dooley, Brant Firestone, Pascal D. Fortin, John Giraldes, Ty Gould, Joseph D. Growney, Michael D. Jones, Raviraj Kulathila, Fallon Lin, Gang Liu, Arne Mueller, Simon van der Plas, Kelly Slocum, Troy Smith, Remi Terranova, B. Barry Toure, Viraj Tyagi, Trixie Wagner, Xiaoling Xie, Ming Xu, Fan S. Yang, Liping X. Zhou, Raymond Pagliarini, Young Shin Cho
ACS MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Medicinal
Ian Bruce, Mohammed Akhlaq, Graham C. Bloomfield, Emma Budd, Brian Cox, Bernard Cuenoud, Peter Finan, Peter Gedeck, Julia Hatto, Judy F. Hayler, Denise Head, Thomas Keller, Louise Kirman, Catherine Leblanc, Darren Le Grand, Clive McCarthy, Desmond O'Connor, Charles Owen, Mrinalini S. Oza, Gaynor Pilgrim, Nicola E. Press, Lilya Sviridenko, Lewis Whitehead
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2012)
Article
Biochemistry & Molecular Biology
Patrick McCarren, Michelle L. Hall, Lewis Whitehead
CHEMICAL BIOLOGY & DRUG DESIGN
(2012)
Article
Biochemistry & Molecular Biology
Anke Bill, Michelle Lynn Hall, Jason Borawski, Catherine Hodgson, Jeremy Jenkins, Philippe Piechon, Oana Popa, Christopher Rothwell, Pamela Tranter, Scott Tria, Trixie Wagner, Lewis Whitehead, L. Alex Gaither
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Chemistry, Medicinal
Michelle Lynn Hall, William L. Jorgensen, Lewis Whitehead
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2013)
Article
Chemistry, Medicinal
Matthew J. LaMarche, Jennifer A. Leeds, Kerri Amaral, Jason T. Brewer, Simon M. Bushell, Janetta M. Dewhurst, JoAnne Dzink-Fox, Eric Gangl, Julie Goldovitz, Akash Jain, Steve Mullin, Georg Neckermann, Colin Osborne, Deborah Palestrant, Michael A. Patane, Elin M. Rann, Meena Sachdeva, Jian Shao, Stacey Tiamfbok, Lewis Whitehead, Donghui Yu
JOURNAL OF MEDICINAL CHEMISTRY
(2011)
Article
Chemistry, Medicinal
Matthew J. LaMarche, Jennifer A. Leeds, Adam Amaral, Jason T. Brewer, Simon M. Bushell, Gejing Deng, Janetta M. Dewhurst, Jian Ding, JoAnne Dzink-Fox, Gabriel Gamber, Akash Jain, Kwangho Lee, Lac Lee, Troy Lister, David McKenney, Steve Mullin, Colin Osborne, Deborah Palestrant, Michael A. Patane, Elin M. Rann, Meena Sachdeva, Jian Shao, Stacey Tiamfook, Anna Trzasko, Lewis Whitehead, Aregahegn Yifru, Donghui Yu, Wanlin Yan, Qingming Zhu
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Biochemical Research Methods
Paula M. Petrone, Janetta Dewhurst, Ruben Tommasi, Lewis Whitehead, Andrea K. Pomerantz
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2011)
Article
Multidisciplinary Sciences
Beat Nyfeler, Dominic Hoepfner, Deborah Palestrant, Christina A. Kirby, Lewis Whitehead, Robert Yu, Gejing Deng, Ruth E. Caughlan, Angela L. Woods, Adriana K. Jones, S. Whitney Barnes, John R. Walker, Swann Gaulis, Ervan Hauy, Saskia M. Brachmann, Philipp Krastel, Christian Studer, Ralph Riedl, David Estoppey, Thomas Aust, N. Rao Movva, Zuncai Wang, Michael Salcius, Gregory A. Michaud, Gregory McAllister, Leon O. Murphy, John A. Tallarico, Christopher J. Wilson, Charles R. Dean
Article
Pharmacology & Pharmacy
Shawn Zhang, Dan Wu, Liping Zhou
Article
Chemistry, Medicinal
Hanmi Xi, Aiden Zhu, Gerard R. Klinzing, Liping Zhou, Shawn Zhang, Andrew J. Gmitter, Kristin Ploeger, Pavithra Sundararajan, Majid Mahjour, Wei Xu
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Review
Pharmacology & Pharmacy
Bin Yang, Ana Gomes Dos Santos, Sanyogitta Puri, Annette Bak, Liping Zhou
Summary: This article outlines strategies to prolong peptide exposure and reduce dosing frequency, focusing on challenges in drug manufacturing, critical quality attributes, chemistry and design aspects impacting peptide release, and considerations for CMC developability assessments of sustained release peptide drugs.
EXPERT OPINION ON DRUG DELIVERY
(2022)
Review
Biochemistry & Molecular Biology
Charles H. H. Chen, Bing Zan, Jakob P. P. Ulmschneider, William C. C. Wimley, Timothy K. K. Lu, Martin B. B. Ulmschneider, Liping Zhou
Summary: Membrane-active peptides play crucial roles in organisms' immune systems and counter infectious diseases. Despite extensive research, only a few of the over 3500 identified sequences have gained FDA approval. This review investigates successful peptide therapeutics and presents insights into membrane-active anticancer peptide drugs.
JOURNAL OF PEPTIDE SCIENCE
(2023)