Article
Medicine, General & Internal
Mohammed Al-Zubaidi, Pravin Viswambaram, Steve McCombie, Elizabeth Liow, Nat Lenzo, Tom Ferguson, Andrew D. Redfern, Richard Gauci, Dickon Hayne
Summary: Bladder cancer is a lethal disease with limited conventional imaging modalities for accurate staging. This study aims to investigate the use of (89)Zirconium-labelled girentuximab PET in the staging of bladder and urothelial carcinomas.
Article
Chemistry, Medicinal
Ozlem Akgul, Srishti Singh, Jacob T. Andring, Robert McKenna, Silvia Selleri, Fabrizio Carta, Andrea Angeli, Claudiu T. Supuran
Summary: A series of taurine substituted sulfonamide derivatives with ureido moiety at the tail section were synthesized as selective inhibitors of tumor associated human Carbonic Anhydrase (CA) IX and XII. These derivatives showed a strong dependence on the presence of ureido moiety and demonstrated highly stabilized ligand-protein complex with specific amino acid residues in both hCA II and hCA IX-mimic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ashraf K. El-Damasy, Hyun Ji Kim, Alessio Nocentini, Seon Hee Seo, Wagdy M. Eldehna, Eun-Kyoung Bang, Claudiu T. Supuran, Gyochang Keum
Summary: A series of 6-ureido/amidocoumarins were designed and synthesised to develop potent and isoform-selective carbonic anhydrase inhibitors. The target coumarins effectively inhibited tumour-related isoforms hCA IX and hCA XII, while not inhibiting cytosolic off-target isoforms hCA I and II. The most promising compound, 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, showed the best anticancer activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Elena Andreucci, Alessio Biagioni, Sara Peri, Giampaolo Versienti, Fabio Cianchi, Fabio Staderini, Lorenzo Antonuzzo, Claudiu T. Supuran, Erika Olivo, Elisa Pasqualini, Luca Messerini, Daniela Massi, Matteo Lulli, Jessica Ruzzolini, Silvia Peppicelli, Francesca Bianchini, Nicola Schiavone, Lido Calorini, Lucia Magnelli, Laura Papucci
Summary: Gastric cancer is a common malignancy with high mortality rates, mainly due to the development of chemoresistance. Carbonic anhydrase IX (CAIX) has been identified as a potential biomarker associated with poor prognosis in various solid cancers. In this study, it was found that non-responder gastric cancer patients and drug-resistant gastric cancer cell lines showed increased expression of CAIX compared to responder patients and control cells, respectively. Furthermore, a drug called SLC0111 was found to improve the therapy response of both wild-type and resistant gastric cancer cells, suggesting its potential in overcoming chemoresistance.
Article
Biochemistry & Molecular Biology
Lamya H. Al-Wahaibi, Bahaa G. M. Youssif, Ehab S. Taher, Ahmed H. Abdelazeem, Antar A. Abdelhamid, Adel A. Marzouk
Summary: A novel series of tri-aryl imidazole derivatives carrying benzene sulfonamide moiety were designed for their selective inhibitory activity against hCA IX and XII. Among them, six compounds showed potent and selective CA IX inhibition, with 5g and 5b demonstrating higher antiproliferative activity compared to other tested compounds. Docking studies of these two compounds revealed their favorable binding interactions with CA-IX, similar to that of ligand 9FK. Molecular modeling simulations supported the biological evaluation results.
Article
Biochemistry & Molecular Biology
Davide Moi, Serena Vittorio, Andrea Angeli, Gianfranco Balboni, Claudiu T. Supuran, Valentina Onnis
Summary: A series of hydrazonobenzenesulfonamides were designed, synthesized and evaluated for their inhibitory activity against human carbonic anhydrase (hCA) isoforms. The synthesized compounds showed inhibitory activity at low nanomolar levels against hCA I, II, IX and XII, with selectivity against hCA II isoform, as well as hCA IX and XII isoforms. Docking studies were conducted to understand the activity and selectivity of the most potent and selective hydrazones towards different CA isoforms.
Article
Chemistry, Multidisciplinary
Jingjing Wang, Zhaoli Sun, Shuren Wang, Chenyang Zhao, Junjie Xu, Shen Gao, Meng Yang, Fugeng Sheng, Song Gao, Yanglong Hou
Summary: The study introduces a tumor therapy strategy that disrupts intratumoral metabolic symbiosis by inducing acidosis for tumor elimination, using carbonic anhydrase inhibitor-modified ferrous sulfide nanoparticles. The nanoparticles also have dual-mode imaging capabilities.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Analytical
Ririko Nakaoka, Kazuhiro Kato, Kumiko Yamamoto, Hironobu Yasui, Shingo Matsumoto, Igor A. Kirilyuk, Valery V. Khramtsov, Osamu Inanami, Hiroshi Hirata
Summary: Extracellular acidification is a hallmark of tumor malignancy, and non-invasive mapping of extracellular pH (pHe) is essential for understanding the tumor microenvironment and monitoring tumor response to metabolism-targeting drugs. A modified electron paramagnetic resonance (EPR) system achieves higher sensitivity in mapping pHe and can be used to monitor the response of other metabolism-targeting drugs.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Analytical
Jun Yan, Kaizhen Wang, Lijuan Gui, Xian Liu, Yingying Ji, Jingjing Lin, Man Luo, Hong Xu, Jingxuan Lv, Fang Tan, Liangting Lin, Zhenwei Yuan
Summary: Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. In this study, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). The probe showed excellent sensitivity and selectivity and demonstrated good biosafety in both cells and mice. Furthermore, the probe was successfully applied for NTR detection in orthotopic lung tumor models.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Nian Liu, Qian Lin, Wenbao Zuo, Weibin Chen, Shan Huang, Yinshu Han, Xing-Jie Liang, Xuan Zhu, Shuaidong Huo
Summary: We reported a carbonic anhydrase IX-targeted nanovesicle to enhance ferroptosis by remodeling the intracellular environment. This nanovesicle could be internalized by cancer cells specifically through CA IX targeting. By inducing intracellular acidification and altering redox homeostasis, the nanovesicle promoted lipid peroxidation to aggravate ferroptosis. In addition, the nanovesicle contained hemoglobin as an iron reservoir and released oxygen to ameliorate tumor hypoxia, while producing singlet oxygen to enhance photodynamic therapy. This study provides a promising paradigm for designing nanomedicines to enhance ferroptosis-based synergistic therapeutics.
NANOSCALE HORIZONS
(2023)
Article
Biochemical Research Methods
Michael Mortensen, Marco Bertolini, Jacqueline Mock, Jorg Scheuermann, Sebastian Oehler
Summary: The delivery of bioactive proteins for cancer immunotherapy often relies on antibodies or antibody fragments. However, fusion proteins may have low tissue penetration due to their large size. Small molecule ligands that target tumor-associated antigens provide a potential alternative for selective delivery of cytokines to tumor lesions.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shafi Mahmud, Ekhtiar Rahman, Zulkar Nain, Mutasim Billah, Sumon Karmakar, Sumon Chandro Mohanto, Gobindo Kumar Paul, Al Amin, Uzzal Kumar Acharjee, Md. Abu Saleh
Summary: The study screened 42 plant-derived compounds and identified three with higher binding affinity, potentially serving as potent hCAIX inhibitors. Further experimental validation of these potential inhibitors could effectively target the hCAIX protein, paving the way for prospective anticancer therapeutics.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Pharmacology & Pharmacy
Mengmeng Lu, Xiaokang Zhang, Xiaoge Gao, Shishuo Sun, Xiaohuan Wei, Xiaolei Hu, Chao Huang, Heng Xu, Bixi Wang, Wei Zhang, Zhen Li, Xinhui Feng, Junnian Zheng, Qing Zhang
Summary: The study reveals novel antitumor mechanisms of Lenvatinib by enhancing T cell-mediated antitumor immunity, with the drug increasing T cell proliferation, infiltration, and activity while decreasing the frequency and activity of immunosuppressive cells. Additionally, Lenvatinib enhances the efficacy of CAR-T cells in a murine renal cancer model, suggesting potential for future combination therapy.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Marta Meneghello, Ana Rita Oliveira, Aurore Jacq-Bailly, Ines A. C. Pereira, Christophe Leger, Vincent Fourmond
Summary: Mo/W formate dehydrogenases catalyze the reversible reduction of CO2 to formate, and it has been definitively demonstrated through an electrochemical method that the substrate is indeed CO2, not a hydrated species like HCO3-.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Oncology
Yongjun Yang, Xiaoting Yan, Jiawei Li, Chao Liu, Xiaofeng Yang
Summary: Transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the most effective strategy for the management of non-muscle-invasive bladder cancer worldwide. Visual enhancement using targeted optical molecular imaging and near-infrared photoimmunotherapy (NIR-PIT) show the potential to detect and remove all tumors, reduce tumor recurrence rates, and inhibit the growth of recurrent tumors.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biochemistry & Molecular Biology
Amresh Prakash, Vijay Kumar, Atanu Banerjee, Andrew M. Lynn, Rajendra Prasad
Summary: The second RNA recognition motif (RRM2) of TDP-43 plays a major role in aggregation and toxicity, with multiple metastable intermediate states stabilized by hydrophobic contacts and hydrogen bonds. The partially unfolded states exhibit increased aggregation propensity due to exposure of aggregation-prone beta-sheets, shedding light on TDP-43 misfolding and aggregation mechanisms.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Preeti Pandey, Jitendra Subhash Rane, Aroni Chatterjee, Abhijeet Kumar, Rajni Khan, Amresh Prakash, Shashikant Ray
Summary: This study investigated the interaction of 10 potential naturally occurring compounds with the SARS-CoV-2 spike protein, indicating their potential to disrupt the binding of the hACE2-S complex. Molecular docking studies and molecular dynamics simulation suggested that flavonoids and non-flavonoids may serve as anti-SARS-CoV-2 agents with drug-likeness properties.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Jitendra Subhash Rane, Preeti Pandey, Aroni Chatterjee, Rajni Khan, Abhijeet Kumar, Amresh Prakash, Shashikant Ray
Summary: The global human population is currently dealing with the horrific impact of the COVID-19 pandemic, and research targeting the spike glycoprotein of the virus for drug development holds significant therapeutic potential in combatting infection. This study used computational techniques to identify potential inhibitors that disrupt the interaction between the spike glycoprotein and the hACE2 receptor, providing a promising avenue for future antiviral drug development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Nanoscience & Nanotechnology
Anirudh Singh, Arushi Verma, Ruhar Singh, Amaresh Kumar Sahoo, Sintu Kumar Samanta
Summary: This study attempts to develop an alternative strategy to address bacterial antibiotic resistance issues by synthesizing biogenic C-dots combined with lysozymes to form C-dots carrier (CDC), encapsulated in chitosan as a delivery system. The CDC demonstrates synergistic bactericidal activity against antibiotic-resistant bacteria, prevents biofilm formation, eradicates preformed biofilm, and shows hemocompatibility for in vivo applications. The combination therapy of C-dots and lysozyme may serve as an excellent antibacterial and antibiofilm strategy.
Article
Biochemical Research Methods
Chandra Bhushan Mishra, Preeti Pandey, Ravi Datta Sharma, Md Zubbair Malik, Raj Kumar Mongre, Andrew M. Lynn, Rajendra Prasad, Raok Jeon, Amresh Prakash
Summary: The study identified seven drugs that preferentially bind to target proteins of SARS-CoV-2, among which catechin showed effective binding to multiple target proteins with favorable molecular interactions. The molecular dynamics simulations revealed the potential of catechin as a multi-targeted agent against COVID-19.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Isabel Regadas, Olle Dahlberg, Roshan Vaid, Oanh Ho, Sergey Belikov, Gunjan Dixit, Sebastian Deindl, Jiayu Wen, Mattias Mannervik
Summary: The study identified a unique chromatin state with histone 3 lysine 14 acetylation in key tissue-specific genes in Drosophila and human cells. Functional experiments demonstrated that H3K14 is essential for the expression of genes lacking canonical histone modifications, highlighting its crucial role in tissue-specific gene regulation.
Article
Cell Biology
Neha Atale, Chandra Bhushan Mishra, Shrey Kohli, Raj Kumar Mongre, Amresh Prakash, Sweta Kumari, Umesh C. S. Yadav, Raok Jeon, Vibha Rani
Summary: The study showed that S. cumini methanol seed extract could suppress gelatinase-B expression and activity in diabetes-induced cardiomyopathy, as well as reduce the activation of NF-kappa B, TNF-alpha, and IL-6. In silico docking studies indicated a strong interaction between S. cumini polyphenols and gelatinase-B, suggesting the potential use of MSE as a functional food and dietary supplement for regulating cardiac stress induced by high glucose.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Multidisciplinary Sciences
Gunjan Dixit, Ying Zheng, Brian Parker, Jiayu Wen
Summary: This article demonstrates how RNA-seq data can be utilized to explore differential exon and polyadenylation site usage to understand gene regulation at the post-transcriptional level. By utilizing specific packages and functions, differential analysis and visualization of these mechanisms can be identified step by step.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Neurosciences
Ruiting Li, Ruhar Singh, Tara Kashav, ChunMin Yang, Ravi Datta Sharma, Andrew M. Lynn, Rajendra Prasad, Amresh Prakash, Vijay Kumar
Summary: This study investigated the folding and unfolding of the N-terminal domain (NTD) of TDP-43 protein at high temperatures using molecular dynamics simulations. Results showed that the unfolding process of NTD at high temperature involved the formation of different conformational states with varying stability and free energy. The presence of structurally heterogeneous intermediate ensembles during unfolding may facilitate NTD oligomerization and subsequent TDP-43 oligomerization.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ruhar Singh, Abhijeet Kumar, Jitendra Subhash Rane, Rajni Khan, Garima Tripathi, Amrendra K. Ajay, Amresh Prakash, Shashikant Ray
Summary: The vaccination drive against COVID-19 worldwide was successful, but the second wave of infections was more severe. New variants of SARS-CoV-2 emerged, which could escape antibodies in convalescent or vaccinated individuals, leading to increased reinfections and deaths. This study identified inhibitors with high binding affinity to the spike glycoprotein and ACE2 receptor of SARS-CoV-2, suggesting their potential as drugs against the virus.
SCIENTIFIC REPORTS
(2022)
Review
Biochemical Research Methods
Trishala Das, Harbinder Kaur, Pratibha Gour, Kartikay Prasad, Andrew M. Lynn, Amresh Prakash, Vijay Kumar
Summary: This article provides an overview of the application of network medicine and network-based machine learning algorithms in ALS, aiming to identify new disease genes, critical pathways, and personalized treatment targets for ALS.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Dailu Chen, Sofia Bali, Ruhar Singh, Aleksandra Wosztyl, Vishruth Mullapudi, Jaime Vaquer-Alicea, Parvathy Jayan, Shamiram Melhem, Harro Seelaar, John C. van Swieten, Marc I. Diamond, Lukasz A. Joachimiak
Summary: This study reveals the structural mechanism underlying spontaneous aggregation of FTD-tau mutant S320F, using a combination of in vitro, in silico, and cellular experiments. The study shows that S320F stabilizes a local hydrophobic cluster, exposing the amyloid motif (306)VQIVYK(311); identifies a suppressor mutation that reverses the phenotype in vitro and in cells; and computationally optimizes nonpolar clusters surrounding the S320 position to engineer tau sequences that spontaneously aggregate. This research uncovers a mechanism for regulating tau aggregation and may contribute to the design of reagents targeting disease-specific tau conformations.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Satabdi Saha, Rakesh Srivastava, Parishmita Sarma, Tarun Kumar Bhatt, Amresh Prakash, Diwakar Kumar
Summary: Leishmania donovani is the causative agent of neglected tropical disease visceral leishmaniasis. A study examined three natural compounds, apigenin, diosmin, and naringin, as potential inhibitors against the Leishmania donovani Sterol 24-C- methyltransferase enzyme. The compounds showed high affinity for the enzyme and demonstrated excellent IC50 values in cell viability assays.
MOLECULAR SIMULATION
(2023)
Meeting Abstract
Biophysics
Ruhar Singh, Atanu Banerjee, Amresh Prakash, Andrew M. Lynn
BIOPHYSICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Chandra Bhushan Mishra, Raj Kumar Mongre, Amresh Prakash, Raok Jeon, Claudiu T. Supuran, Myeong-Sok Lee
Summary: BSM-0004, a novel hCA IX inhibitor, demonstrated potent anticancer effects in breast cancer cells by inducing apoptosis. It also significantly regulated the expression of crucial biomarkers associated with apoptosis. Moreover, in vivo studies showed that BSM-0004 effectively reduced tumor growth in a xenograft cancer model.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
