Article
Biochemistry & Molecular Biology
Jung-Chun Chu, Hui-Ju Tseng, Sung-Bau Lee, Kai-Cheng Hsu, Ling-Wei Hsin, Ru-Hao Liang, Tony Eight Lin, Nain-Chu Gao, Liang-Chieh Chen, Wan-Hsun Lu, Andrew H. -J Wang, Wei-Jan Huang
Summary: This study discovered a series of phenoxazine-containing compounds with C-4 substituents that showed potent inhibitory activities against class II HDACs. Compound 7d exhibited the most potent inhibition and protected neuron cells from H2O2-induced damage. These findings suggest that compound 7d is a promising candidate for the development of anti-neurodegenerative agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Nils Goehringer, Yayi Peng, Bianca Nitzsche, Hannah Biermann, Rohan Pradhan, Rainer Schobert, Marco Herling, Michael Hoepfner, Bernhard Biersack
Summary: The development of new anticancer drugs is essential due to the limitations of current drugs. Histone deacetylases (HDACs) have emerged as promising targets for cancer treatment. SF5-SAHA, a newly synthesized HDAC inhibitor, showed strong inhibition of tumor cell growth and potential for further development as an anticancer drug candidate.
Article
Chemistry, Medicinal
Linlin Dai, Cheng Tan, Hui Wang, Luyao Wang, Ting Zhang, Shuang Zhi, Zibo Yang, Xiumei Zhao, Dongdong Li
Summary: This study successfully synthesized a new series of sophoridine hydroxamic acid derivatives and identified a compound with significant cytotoxicity against triple-negative breast cancer cells. The compound demonstrated inhibitory activity against HDAC1/3/6 and induced apoptosis and S phase cell cycle arrest. Additionally, it was found to block the PI3K/AKT/mTOR signaling pathway and down-regulate the expression of DNMT1, DNMT3a, and DNMT3b.
Article
Chemistry, Multidisciplinary
Tianyi Zhang, Xiaoyan Zhao, Xiangpei Sun, Wei Tian, Chongqing Wang, Mingping Wang, Yi Zhang, Xin Chen, Canhui Zheng
Summary: This study aimed to discover novel HDAC6 selective inhibitors, and a new class of compounds with excellent inhibitory activities and selectivity was obtained through structural optimization of the previously reported inhibitor 7g. These compounds showed inhibitory effects on HDAC6, a protein associated with diseases such as cancer, and may have lower toxicity to normal cells and tissues.
JOURNAL OF SAUDI CHEMICAL SOCIETY
(2022)
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)
Review
Medicine, Research & Experimental
Nasreddine El Omari, Learn-Han Lee, Saad Bakrim, Hafiz A. Makeen, Hassan A. Alhazmi, Syam Mohan, Asaad Khalid, Long Chiau Ming, Abdelhakim Bouyahya
Summary: Romidepsin, a natural molecule produced by Chromobacterium violaceum bacterium, has been approved for its anti-cancer effect. It is a selective histone deacetylase (HDAC) inhibitor that modifies histones and epigenetic pathways. This review aims to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin, which can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Kai-Cheng Hsu, Jung-Chun Chu, Hui-Ju Tseng, Chia- Liu, Hao-Ching Wang, Tony Eight Lin, Hong-Sheng Lee, Ling-Wei Hsin, Andrew H-J Wang, Chien-Huang Lin, Wei-Jan Huang
Summary: The study showed that modifying the acridine ring with phenothiazine derivatives can effectively inhibit the activity of class II HDACs, with compound 4f exhibiting the strongest inhibitory effect and promoting neurite outgrowth.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Ophthalmology
Ruchi P. Patel, Joanna R. Thomas, Katherine M. Curt, Christina M. Fitzsimmons, Pedro J. Batista, Susan E. Bates, Michael M. Gottesman, Robert W. Robey
Summary: The combination of romidepsin with mTOR inhibitors was found to effectively induce apoptosis in uveal melanoma cell lines by increasing caspase-3 and PARP cleavage. RNA sequencing analysis revealed significant changes in the apoptosis pathway, with increased pro-apoptotic gene BCL2L11 and decreased anti-apoptotic genes BIRC5 and BCL2L1 at the protein level in response to this combination treatment.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
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
Biochemistry & Molecular Biology
Lin Zhang, Yiming Chen, Fahui Li, Lihui Zhang, Jinhong Feng, Lei Zhang
Summary: Histone deacetylases (HDACs) are important targets for the development of anticancer drugs. The 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment plays a crucial role in the structure of HDAC inhibitors. Compound L20 exhibited selective inhibition against HDAC1, HDAC2, and HDAC3, while showing lower activity against HDAC6. It also demonstrated inhibitory effects on both hematological and solid cancers by promoting cell cycle arrest and apoptosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Haon Futamata, Masahiro Fukuda, Rie Umeda, Keitaro Yamashita, Atsuhiro Tomita, Satoe Takahashi, Takafumi Shikakura, Shigehiko Hayashi, Tsukasa Kusakizako, Tomohiro Nishizawa, Kazuaki Homma, Osamu Nureki
Summary: Outer hair cell electromotility, driven by prestin, is essential for mammalian cochlear amplification. In this study, the cryo-EM structures of thermostabilized prestin in the presence of different anions are reported, providing insights into the mechanisms of mammalian cochlear amplification.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ping-Ting Mao, Wei-Bao He, Xi Mai, Li-Hua Feng, Na Li, Yi-Jing Liao, Cai-Sheng Zhu, Jian Li, Ting Chen, Shu-Hao Liu, Qi-Ming Zhang, Ling He
Summary: The aminobenzamide compounds with 9-substituted purine selectively inhibit class I HDACs and exhibit excellent inhibitory activity on cancer cells, particularly compound 9d. Compound 9d is 12 times more potent than MS-275 against HDAC1 isoform and has better metabolic stability compared to the well-known HDAC inhibitor SAHA.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Markus Schweipert, Niklas Jaensch, Neha Upadhyay, Kalpana Tilekar, Ewelina Wozny, Sidra Basheer, Eva Wurster, Marlene Mueller, C. S. Ramaa, Franz-Josef Meyer-Almes
Summary: The study investigated the molecular recognition of TZD ligands by HDAC4 and found that these ligands act as competitive inhibitors with a two-step mechanism involving principal recognition and induced fit. Furthermore, the binding kinetics of the ligands can be tuned by varying the structure of the CAP group.
Article
Chemistry, Multidisciplinary
Duong T. Anh, Pham-The Hai, Le D. Huy, Hoang B. Ngoc, Trinh T. M. Ngoc, Do T. M. Dung, Eun J. Park, In K. Song, Jong S. Kang, Joo-Hee Kwon, Truong T. Tung, Sang-Bae Han, Nguyen-Hai Nam
Summary: Novel N-hydroxypropenamide compounds based on 4-oxoquinazoline were designed, synthesized, and evaluated for their inhibitory and cytotoxic activities against histone deacetylase (HDAC). The derivatives with N-3-benzyl substitution showed stronger bioactivity compared to N-3-alkyl substitution. Compounds 101 and 10m exhibited the most potent HDAC inhibitory activity and cytotoxicity.
Review
Chemistry, Physical
Jinjiao Dong, Xinyue Zhu, Wei Yu, Xiaotong Hu, Yiwen Zhang, Kan Yang, Zhihao You, Zhenming Liu, Xiaoqiang Qiao, Yali Song
Summary: A series of pyrazolo [3,4-d]pyrimidine-based dual HDAC/Topo II inhibitors were synthesized, showing excellent dual inhibitory activities against HDAC and Topo II. These compounds displayed potent cytotoxicity in cancer cell lines and inhibited the migration of MCF-7 cells. Further studies revealed that compounds 12 and 24 promoted apoptosis in MCF-7 cells and showed significant interaction with active sites of HDAC and Topo II.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Daniel P. Dowling, Zachary D. Miles, Caroline Kohrer, Stephanie J. Maiocco, Sean J. Elliott, Vahe Bandarian, Catherine L. Drennan
NUCLEIC ACIDS RESEARCH
(2016)
Article
Multidisciplinary Sciences
Daniel P. Dowling, Yan Kung, Anna K. Croft, Koli Taghizadeh, Wendy L. Kelly, Christopher T. Walsh, Catherine L. Drennan
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Biochemistry & Molecular Biology
Daniel P. Dowling, Stephanie L. Gantt, Samuel G. Gattis, Carol A. Fierke, David W. Christianson
Article
Biochemistry & Molecular Biology
Daniel P. Dowling, Monica Ilies, Kellen L. Olszewski, Silvia Portugal, Maria M. Mota, Manuel Llinas, David W. Christianson
Review
Biochemistry & Molecular Biology
Daniel P. Dowling, Jessica L. Vey, Anna K. Croft, Catherine L. Drennan
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2012)
Review
Biochemistry & Molecular Biology
D. P. Dowling, L. Di Costanzo, H. A. Gennadios, D. W. Christianson
CELLULAR AND MOLECULAR LIFE SCIENCES
(2008)
Article
Biochemistry & Molecular Biology
Daniel P. Dowling, Nathan A. Bruender, Anthony P. Young, Reid M. McCarty, Vahe Bandarian, Catherine L. Drennan
NATURE CHEMICAL BIOLOGY
(2014)
Article
Biochemistry & Molecular Biology
Jeremy J. M. Liew, Israa M. El Saudi, Son Nguyen, Denyce K. Wicht, Daniel P. Dowling
Summary: Crystal structures of the Pseudomonas fluorescens MsuD were reported, elucidating its role as an alkanesulfonate monooxygenase and revealing the critical importance of the protein C terminus in stabilizing tetramer formation and the alkanesulfonate-binding site. The study provides a deeper understanding of the functionality of MsuD at the molecular level within the sulfur assimilation pathway.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Subrata H. Mishra, Aswani K. Kaneherla, Kenneth A. Marinein, Guillaume Bouvignies, Santrupti Nerli, Nikolaos Sgourakis, Daniel P. Dowling, Dominique P. Frueh
Summary: This study demonstrates the importance of global structural fluctuations in nonribosomal peptide synthetases (NRPSs), which play a role in substrate-dependent communication and allosteric responses. The findings also suggest that impeding these global dynamics can hinder molecular recognition and allostery.