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, 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
Medicine, Research & Experimental
Lei Hou, Yunchang Zhang, Ying Huang, Zhen Fang, Guangze Sang, Tianheng Chen, Zhiqiang Ma, Feng Yang
Summary: The synthesis of dual-mode antitumor molecules combining photodynamic therapy and chemotherapy has shown promising results in inhibiting tumor growth and metastasis. Compound 4, with favorable phototoxicity and dark toxicity, demonstrated the best inhibitory effect on tumor growth and migration, making it a potential photosensitizer and HDACi.
MOLECULAR PHARMACEUTICS
(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)
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
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
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)
Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Svetlana Sharifulina
Summary: HDAC and HAT play crucial roles in regulating cell functions through acetylating/deacetylating histones and non-histone proteins, impacting cell survival, death, and other processes. The effects of stroke on non-histone protein acetylation/deacetylation in brain cells are still poorly understood, but HDAC inhibitors have shown promise in protecting the brain from ischemic damage. The roles of different HDAC isoforms in brain cell survival and death after stroke remain controversial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Xin-Hui Zhang, Qin-Ma, Hui-Pan Wu, Mussa Yussuf Khamis, Yi-Han Li, Li-Ying Ma, Hong-Min Liu
Summary: In this translation, the essential role of HDACs in maintaining homeostasis is discussed, with a focus on the unique characteristics and diverse functions of HDAC6. HDAC6 inhibitors have shown promising potential in treating various diseases with reduced toxicity. Progress has been made in defining the crystal structures of HDAC6 catalytic domains, which can inform the development of HDAC6 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Ye Yang, Baichun Hu, Yi Yang, Kaihua Gong, Huibin Wang, Qi Guo, Xinjie Tang, Yujuan Li, Jian Wang
Summary: The study utilized various computational methods to clarify the structural basis of selective inhibition towards HDAC2 over HDAC8 and demonstrated the different binding modes of inhibitors with the two isoforms. The results revealed the diverse interaction patterns of HDAC2 and HDAC8 inhibitors with Zn2+ ions.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Oncology
Weiyu Dai, Side Liu, Jieming Zhang, Miaomiao Pei, Yizhi Xiao, Jiaying Li, Linjie Hong, Jianjiao Lin, Jing Wang, Xiaosheng Wu, Guangnan Liu, Yaying Chen, Yusi Wang, Zhizhao Lin, Qiong Yang, Fachao Zhi, Guoxin Li, Weimei Tang, Aimin Li, Li Xiang, Jide Wang
Summary: miR-769-5p/miR-769-3p acts as a tumor suppressor in gastric cancer by targeting IGF1R and through the STAT3-IGF1R-HDAC3 complex. Treatment with the HDAC inhibitor SAHA triggers the expression of miR-769-5p/miR-769-3p, leading to inhibition of proliferation and induction of apoptosis in gastric cancer cells.
Review
Medicine, General & Internal
Dimitrios Goutas, Stamatios Theocharis, Gerasimos Tsourouflis
Summary: HDACs play important roles in tumorigenesis and tumor progression, showing potential as therapeutic targets in cancer treatment. However, their clinical significance as biomarkers in cancer is not fully elucidated. This study aims to emphasize the clinical significance of HDAC isoform expression in different tumor types and their correlations with clinicopathological parameters and patient outcomes.
Review
Biochemistry & Molecular Biology
Marta Halasa, Kamila Adamczuk, Grzegorz Adamczuk, Syeda Afshan, Andrzej Stepulak, Marek Cybulski, Anna Wawruszak
Summary: N-ε-lysine acetylation/deacetylation is a common post-translational modification regulated by histone acetyltransferases and histone deacetylases, influencing the properties and functions of histones and non-histone proteins, including transcription factors that alter cell signaling pathways and impact cancer progression. HDACs play a significant role in deacetylating targets, leading to the regulation of proteins involved in cell cycle and apoptosis, ultimately affecting tumor growth, invasion, and drug resistance. This review highlights the clinical importance of epigenetic modifications as a potential therapeutic target in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Mousumi Shyam, Harshita Verma, Gourab Bhattacharje, Piyali Mukherjee, Samsher Singh, Sujit Kamilya, Pushpendu Jalani, Swetarka Das, Arunava Dasgupta, Abhishake Mondal, Amit Kumar Das, Amit Singh, Federico Brucoli, Claire Bagneris, Rachael Dickman, Vinay N. Basavanakatti, Patibandla Naresh Babu, Vadivelan Sankaran, Abhimanyu Dev, Barij Nayan Sinha, Sanjib Bhakta, Venkatesan Jayaprakash
Summary: In this study, pyrazoline analogues were designed and synthesized to mimic the structure of Mycobactin. Compounds 44 and 49 were identified as potential mycobactin biosynthesis inhibitors against mycobacteria, demonstrating effective eradication of intracellular mycobacteria. These compounds also showed stronger efflux pump inhibition compared to known inhibitors. This study provides a new strategy for combating antimicrobial resistance challenges.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Sheikh Murtuja, Deepak Shilkar, Biswatrish Sarkar, Barij Nayan Sinha, Venkatesan Jayaprakash
Summary: This article provides a detailed analysis of each case of design and development of peptide inhibitors against DENV NS2B-NS3 protease in the past two decades. The reasons for their inhibitory activity are discussed, and suggestions to improve the inhibitory activity are highlighted whenever possible.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2022)
Review
Cardiac & Cardiovascular Systems
Amrita Chatterjee, Rajdeep Saha, Arpita Mishra, Deepak Shilkar, Venkatesan Jayaprakash, Pawan Sharma, Biswatrish Sarkar
Summary: Since 2019, the novel coronavirus SARS-CoV-2 has caused an unprecedented pandemic worldwide. It has led to significant damage to multiple organs, including the lungs and heart. The disease is complicated by cardiovascular injury, hypoxia-induced myocardial injury, and systemic inflammatory responses. This review examines the impact of COVID-19 on cardiovascular health, comorbidities, and post-immunization cardiovascular complications.
CURRENT PROBLEMS IN CARDIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mousumi Shyam, Deepak Shilkar, Gourav Rakshit, Venkatesan Jayaprakash
Summary: This article discusses the opportunities to develop new drugs and prolong the shelf life of existing therapeutics by targeting the conditionally essential pathways inside Mycobacterium. The article emphasizes the bottlenecks in fast-tracking antitubercular drug discovery and proposes some strategies for new drug development.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Physical
Abhishek Thakur, Gaurav Sharma, Vishnu Nayak Badavath, Venkatesan Jayaprakash, Kenneth M. Merz, Galia Blum, Orlando Acevedo
Summary: The COVID-19 outbreak has caused massive devastation worldwide, with millions of infections and deaths reported. Using a combination of crystal structures and validated inhibitors, four rules for designing potent inhibitors of SARS-CoV-2 main protease have been proposed. Experimental examination identified a potential lead compound with higher potency than known inhibitors.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Gourav Rakshit, Venkatesan Jayaprakash
Summary: This study investigated the potential of a reported antitubercular molecule as an inhibitor for HIV-1 and nCOVID-19, leading to the discovery of a multi-targeted inhibitor for triple co-infections. The results showed strong binding of the molecule to the target proteins, as well as stability throughout the simulation. In silico ADMET results also indicated satisfactory pharmacokinetic properties. Overall, this computational study identified a potential molecule for further exploration and development of inhibitors against triple infections.
STRUCTURAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ayse Tarbin Jannuzzi, Ayse Mine Yilmaz Goler, Nilufer Bayrak, Mahmut Yildiz, Hatice Yildirim, Betul Karademir Yilmaz, Deepak Shilkar, Raghusrinivasan Jayaprakash Venkatesan, Venkatesan Jayaprakash, Amac Fatih TuYuN
Summary: Using plastoquinone analogs as lead structures, the investigation of brominated PQ analogs in multiple cancer cell lines has revealed significant growth inhibition effects. These analogs exhibit favorable drug-like properties and have the potential to interact with proteasome catalytic subunits. In vitro assays have shown that brominated PQ analogs induce cytotoxicity by causing cell cycle arrest and oxidative stress. These findings offer valuable insights for the development of novel antiproliferative agents.
Article
Chemistry, Physical
Vishnu Nayak Badavath, Abhishek Thakur, Deepak Shilkar, Chandrani Nath, Orlando Acevedo, Gulberk Ucar, Venkatesan Jayaprakash
Summary: In this study, a series of pyrazoline derivatives with a bioisostere methyl group replacing the chloro group on the 5-phenyl ring were synthesized and tested for hMAO inhibitory activity. Compound IIIa showed potent and selective inhibition of hMAO-A, along with strong antioxidant properties, indicating its potential in treating depressive illness and neurodegenerative disorders.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Venkatesan Jayaprakash, Thangavelu Saravanan, Karuppaiyan Ravindran, Thangavelu Prabha, Jubie Selvaraj, Sudeepan Jayapalan, M. V. N. L. Chaitanya, Thangavel Sivakumar
Summary: In this study, a new open-source data analysis Python script was used to discover lead compounds for anticancer drugs by building a QSAR model using 53 thiazole derivatives. Machine learning approaches were employed, and the performance of the model was evaluated using three different algorithms.
CURRENT COMPUTER-AIDED DRUG DESIGN
(2023)
Article
Chemistry, Multidisciplinary
Hatice Yildirim, Nilufer Bayrak, Mahmut Yildiz, Emel Mataraci-Kara, Serol Korkmaz, Deepak Shilkar, Venkatesan Jayaprakash, Amac Faith Tuyun
Summary: This study identified aminated quinolinequinones as potential candidates for novel antibacterial and/or antifungal agents. Some of the compounds demonstrated antimicrobial activity against selected bacterial and fungal strains. AQQ6 and AQQ9 were active against Enterococcus faecalis, while AQQ8 and AQQ9 showed activity against Staphylococcus aureus. AQQ8 and AQQ9 were identified as promising lead molecules for further exploration of their mode of action and antimicrobial activity against biofilm-forming microbes.
Article
Chemistry, Medicinal
Antonio Laghezza, Carmen Cerchia, Massimo Genovese, Rosalba Leuci, Erica Pranzini, Alice Santi, Leonardo Brunetti, Luca Piemontese, Paolo Tortorella, Abanish Biswas, Ravi Pratap Singh, Suhas Tambe, Sudeep Ca, Ashok Kumar Pattnaik, Venkatesan Jayaprakash, Paolo Paoli, Antonio Lavecchia, Fulvio Loiodice
Summary: A new ligand 10 was identified, which can potently activate both PPAR alpha and -gamma subtypes as full and partial agonists, respectively. Docking studies were performed to explain the different effects on the two targets. In vivo experiments showed that compound 10 significantly reduced blood glucose and lipid levels in diabetic mouse models without toxic effects, and further investigation revealed its inhibitory effect on the mitochondrial pyruvate carrier, suggesting its potential for treating dyslipidemic type 2 diabetes as a new class of drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Shilan Zhang, Sabeeta Kapoor, Chakrapani Tripathi, Jorge Tovar Perez, Nivedhitha Mohan, Wan Mohaiza Dashwood, Ke Zhang, Praveen Rajendran, Roderick Dashwood
NPJ PRECISION ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Deepak Shilkar, Mohd Usman Mohd Siddique, Silvia Bua, Sabina Yasmin, Mrunali Patil, Ajay Kumar Timiri, Claudiu T. Supuran, Venkatesan Jayaprakash
Summary: A series of phthalimide-capped benzene sulphonamides (1-22) were evaluated for their inhibitory activity against carbonic anhydrase I (hCA I) and carbonic anhydrase II (hCA II). Compound 1 showed potent inhibitory activity against both hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), with 10 and 6 times higher potency than the standard inhibitor, acetazolamide. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Sayanti Halder, Abhishek Thakur, Supriya Suman Keshry, Pradip Jana, Divyanshi Karothia, Indrani Das Jana, Orlando Acevedo, Rajeeb K. Swain, Arindam Mondal, Soma Chattopadhyay, Venkatesan Jayaprakash, Abhimanyu Dev
Summary: The article introduces an aptamer-based system with diagnostic and therapeutic potential against COVID-19. Aptamer R is shown to specifically inhibit the entry of SARS-CoV-2 virus, and its antiviral potential is tested and analyzed. The study also investigates the intermolecular interactions between the aptamers and the virus domain.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
