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, 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
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, 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
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)
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
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)
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)
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)
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
Oncology
Qian Zhao, Shan-Shan Xiong, Can Chen, Hong-Ping Zhu, Xin Xie, Cheng Peng, Gu He, Bo Han
Summary: The authors designed and synthesized a series of compounds with dual inhibitory activity against MDM2 and HDAC, and found that compound 11b exhibited the strongest inhibition against both targets. This compound also showed effective antiproliferative activity towards MCF-7 cells and increased the expression of p53 and Ac-H4. These results suggest that dual inhibition of HDAC and MDM2 may provide a novel and efficient strategy for the discovery of antitumor drugs in the future.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Clemens Zwergel, Elisabetta Di Bello, Rossella Fioravanti, Mariarosaria Conte, Angela Nebbioso, Roberta Mazzone, Gerald Brosch, Ciro Mercurio, Mario Varasi, Lucia Altucci, Sergio Valente, Antonello Mai
Summary: A series of HDAC inhibitors were synthesized, among which the nicotinic hydroxamate 11d showed the highest inhibitory activity and selectivity, while the nicotinic anilide 12d exhibited the best inhibitory effect on HDAC3. These compounds showed significant anti-proliferative activity in leukemia cells and other cancer cell lines.
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
Infectious Diseases
Aaron James Heffernan, Fekade Bruck Sime, Jing Sun, Jeffrey Lipman, Anand Kumar, Katherine Andrews, David Ellwood, Keith Grimwood, Jason Roberts
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2020)
Article
Microbiology
Fiona J. McCallum, Geoffrey W. Birrell, Marina Chavchich, Ivor Harris, Nicanor Obaldia, Karin Van Breda, Gavin D. Heffernan, David P. Jacobus, Dennis Shanks, Michael D. Edstein
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Microbiology
Aaron J. Heffernan, Fekade B. Sime, Derek S. Sarovich, Michael Neely, Yarmarly Guerra-Valero, Saiyuri Naicker, Kyra Cottrell, Patrick Harris, Katherine T. Andrews, David Ellwood, Steven C. Wallis, Jeffrey Lipman, Keith Grimwood, Jason A. Roberts
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2020)
Article
Infectious Diseases
Nicanor Obaldia, Marlon Nunez
Article
Microbiology
Gillian M. Fisher, Simon A. Cobbold, Andrew Jezewski, Emma F. Carpenter, Megan Arnold, Annie N. Cowell, Erick T. Tjhin, Kevin J. Saliba, Tina S. Skinner-Adams, Marcus C. S. Lee, Audrey Odom John, Elizabeth A. Winzeler, Malcolm J. McConville, Sally-Ann Poulsen, Katherine T. Andrews
Article
Infectious Diseases
Lucas E. Buyon, Ana Maria Santamaria, Angela M. Early, Mario Quijada, Itza Barahona, Jose Lasso, Mario Avila, Sarah K. Volkman, Matthias Marti, Daniel E. Neafsey, Nicanor Obaldia III
PLOS NEGLECTED TROPICAL DISEASES
(2020)
Article
Parasitology
Eva Hesping, Tina S. Skinner-Adams, Gillian M. Fisher, Thomas Kurz, Katherine T. Andrews
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2020)
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
Pharmacology & Pharmacy
Aaron J. Heffernan, Fekade B. Sime, Sazlyna Mohd Sazlly Lim, Saiyuri Naicker, Katherine T. Andrews, David Ellwood, Jeffrey Lipman, Keith Grimwood, Jason A. Roberts
Summary: The study found that simulating the components of the epithelial lining fluid antagonizes the bactericidal effect of amikacin on P. aeruginosa, even at high concentrations achieved.
Article
Infectious Diseases
Aaron James Heffernan, Fekade Bruck Sime, Saiyuri Naicker, Katherine Andrews, David Ellwood, Yarmarly Guerra-Valero, Steven Wallis, Jeffrey Lipman, Keith Grimwood, Jason Alexander Roberts
Summary: The study compared the bacterial killing of once- versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and found that 800 mg once-daily dose achieved >2-log reduction in bacterial burden within the first 24 hours. There was no difference in bacterial killing or regrowth between 3 and 7 days of amikacin therapy, suggesting that 800 mg once-daily for up to 3 days could be considered for future clinical trials.
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
(2021)
Article
Parasitology
M. S. J. Arnold, J. R. Macdonald, R. J. Quinn, T. S. Skinner-Adams, K. T. Andrews, G. M. Fisher
Summary: This study screened 424 natural product derived compounds and identified 46 hit compounds with >50% inhibition against P. falciparum at 10 μM concentration. Among these, nine compounds showed submicromolar activity, with slow action activity confirmed for two compounds, alstonine and himbeline. Both compounds exhibited high selectivity against P. falciparum compared to human cell lines, with no cross-resistance observed in multi-drug resistant lines.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
Article
Parasitology
Ming Jang Chua, Jiahui Tng, Eva Hesping, Gillian M. Fisher, Christopher D. Goodman, Tina Skinner-Adams, Darren Do, Andrew J. Lucke, Robert C. Reid, David P. Fairlie, Katherine T. Andrews
Summary: Research has shown that the anticancer drug HDAC inhibitor AR-42 and its 36 analogues have in vitro activity against Plasmodium parasites, with some compounds showing low cytotoxicity to human cells and high selectivity for the parasites. AR-42 induces hyperacetylation of Plasmodium histone H4 by inhibiting PfHDAC(s), effectively blocking parasite growth inside red blood cells and demonstrating curative properties in oral treatment of experimental mouse malaria.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2021)
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
Infectious Diseases
Nicanor Obaldia, Itza Barahona, Jose Lasso, Mario Avila, Mario Quijada, Marlon Nunez, Matthias Marti
Summary: This study compared the performance of PvLAP5 and Pvs25 qRT-PCR assays to LM for detecting Plasmodium vivax gametocytes in field samples from malaria endemic regions of Panama. Results showed that PvLAP5 qRT-PCR assay is as sensitive and specific as the gold standard Pvs25 assay and at least 37% more sensitive than LM.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Chemistry, Multidisciplinary
Desmond C. M. Sim, Natasha L. Hungerford, Elizabeth H. Krenske, Gregory K. Pierens, Katherine T. Andrews, Tina S. Skinner-Adams, Mary J. Garson
AUSTRALIAN JOURNAL OF CHEMISTRY
(2020)