Article
Chemistry, Multidisciplinary
Dalal Sulaiman Alshaya, Rana M. O. Tawakul, Islam Zaki, Ali H. Abu Almaaty, Eman Fayad, Yasmin M. Abd El-Aziz
Summary: A new series of acrylic acid and acrylate ester derivatives were synthesized and evaluated for their antiproliferative activity against MCF-7 breast carcinoma cells. Methyl acrylate ester 6e showed the highest cytotoxicity with an IC50 value of 2.57 +/- 0.16 mu M and exhibited inhibition of beta-tubulin polymerization. Compound 6e arrested MCF-7 cells at the G2/M phase and enhanced apoptotic power, while also affecting the gene expression levels of p53, Bax, and Bcl-2.
Article
Chemistry, Multidisciplinary
Xuemin Zhao, Rui Zhang, Xiuyan Yu, Na Yu, Yuanze Shi, Mao Shu, Yan Shen
Summary: In this study, a series of new tubulin polymerization inhibitors were designed as potential anti-cancer compounds using 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. Reliable CoMFA and CoMSIA models were established to predict the activities of new inhibitors, and molecular docking and MD simulation were performed to explore the docking mode and interactions between the compounds and receptors. The study provides significant guidance for the design of novel tubulin polymerization inhibitors.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Huajian Zhu, Wenlong Li, Wen Shuai, Yang Liu, Limei Yang, Yuchen Tan, Tiandong Zheng, Hong Yao, Jinyi Xu, Zheying Zhu, Dong-Hua Yang, Zhe-Sheng Chen, Shengtao Xu
Summary: Novel N-benzylbenzamide derivatives 20b and its corresponding disodium phosphate 20b-P show significant anti-cancer activity with excellent safety profile, making them promising anti-tubulin agents for further investigation in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xuchao Yang, Binbin Cheng, Yao Xiao, Mingming Xue, Ting Liu, Hao Cao, Jianjun Chen
Summary: Novel CA-4 analogs were designed, synthesized, and bio-evaluated as dual inhibitors of tubulin polymerization and PD-1/PD-L1, among which TP5 showed strong inhibitory effects against cancer cell lines and moderate anti-PD-1/PD-L1 activity. In vivo efficacy studies demonstrated that TP5 could significantly suppress tumor growth without causing significant toxicity, suggesting its potential as a starting point for developing more potent dual inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Baoxia Liang, Qing Zou, Lintao Yu, Yali Wang, Jun Yan, Baiqi Huang
Summary: Novel indole-containing hybrids derived from Millepachine were synthesized and evaluated for their antitumor activities. Compound 14b showed the most potent cytotoxic activity against human cancer cell lines, being almost 100 times more active than Millepachine. It also demonstrated low cytotoxicity towards normal human cells and equivalent sensitivity towards drug-resistant cells, highlighting its potential for the development of antitumor drugs.
Article
Biochemistry & Molecular Biology
Juan Ma, Guo-Hua Gong
Summary: In this study, a series of novel quinoline sulfonamide derivatives were synthesized and their structures were confirmed. The cytotoxic activities of these compounds against tumor cell lines were evaluated, and one compound showed strong inhibitory effects on cell proliferation and tubulin polymerization. This compound can serve as a lead compound for further studies.
Article
Chemistry, Medicinal
Cheng-Jun Wu, Jia-Qiang Wu, Yunfei Hu, Suyun Pu, Yuying Lin, Zimai Zeng, Jinhui Hu, Wen-Hua Chen
Summary: A series of novel microtubulin polymerization inhibitors based on indole were designed and synthesized, among which compound 12d exhibited the highest antiproliferative activity by inducing cellular apoptosis, cell cycle arrest, and inhibiting tubulin polymerization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Haoxiang Weng, Jinlong Li, Huajian Zhu, Kei Fung Carver Wong, Zheying Zhu, Jinyi Xu
Summary: Microtubules are a major target for inhibiting tumor cell proliferation, and microtubule-targeted agents have become increasingly effective in cancer treatment. Colchicine binding site inhibitors (CBSIs) have a simpler chemical structure than taxane and vinblastine, making them easier to modify. Furthermore, CBSIs have a strong antiproliferative effect on multidrug-resistant tumor cells and have become the mainstream research focus in the development of microtubule-targeted agents.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Heping Zhu, Shilong Ying, Bingluo Zhou, Xiao Liang, Quan He, Ping Song, Xinyang Hu, Keqiang Shi, Mingteng Xiong, Hongchuan Jin, Yuanjiang Pan
Summary: A series of novel 2-aryl-3-sulfonamido-pyridines (HoAns) compounds were designed, synthesized, and evaluated for their antiproliferative activities, with HoAn32 demonstrating the most potent activity and microtubule-targeting effect in cancer cell lines. Mechanism studies showed that HoAn32 bound to the colchicine site of b-tubulin, resulting in multiple anti-cancer effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Vajja Krishna Rao, Anvesh Ashtam, Dulal Panda, Sankar K. Guchhait
Summary: This study investigated the discovery of new tubulin polymerization inhibitors using a natural product-inspired strategy and incorporation of an NP-privileged motif. The synthesized compounds showed significant antiproliferative effects in breast cancer cells, and one compound demonstrated potent inhibitory activity on tubulin polymerization and induction of cell death.
Article
Chemistry, Medicinal
Dong Liang, Chen Yu, Zhao Ma, Mingzhao Hu, Jiahui Wang, Xuhui Dong, Lupei Du, Minyong Li
Summary: In this study, the discovery of two series of parbendazole derivatives as tubulin inhibitors for the treatment of head and neck squamous cell carcinoma (HNSCC) was reported. Compound 9q exhibited the best pharmacological activities and pharmacokinetic properties, displaying reasonable inhibition activity on cell proliferation, induction of cell apoptosis, and suppression of cell migration and invasion.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Guangcheng Wang, Min He, Wenjing Liu, Meiyan Fan, Yongjun Li, Zhiyun Peng
Summary: A series of new 2-phenyl-4,5,6,7-tetrahydro-1H-indole derivatives were synthesized and evaluated for their anti-proliferative activities, with one compound showing the most potent anticancer activity against breast cancer and lung cancer cells while sparing normal liver cells. Mechanism studies revealed that the compound arrested cell cycle and induced apoptosis, and effectively inhibited tubulin polymerization with an inhibitory mechanism similar to colchicine. Molecular docking studies indicated high binding affinities for the colchicine binding pocket of tubulin, suggesting potential as new tubulin polymerization inhibitors.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jingwei Zhou, Yanqing Pang, Weiwei Zhang, Fen OuYang, Haibiao Lin, Xingshu Li, Jun Yan
Summary: Microtubule targeting agents (MTAs) are effective chemotherapies for cancer treatment, but drug resistance remains a challenge. This study discovers that therapy-resistant cancers are vulnerable to ferroptosis, providing an alternative approach to overcome resistance. A compound 33, synthesized based on previous studies, displays potent activity in vitro and in vivo, mainly inducing cell death through ferroptosis rather than apoptosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Medicine, Research & Experimental
Filip Borys, Piotr Tobiasz, Marcin Poterala, Hanna Krawczyk
Summary: This review provides a brief overview of new compounds targeting the dynamic of microtubule-tubulin polymerization/depolymerization. It is divided into three parts focusing on derivatives of stilbene, photoswitchable inhibitors, and macrocyclic compounds as tubulin inhibitors. The authors primarily highlight reports from the past five years and the latest strategies in this field.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Ashish Ranjan Dwivedi, Suraj Singh Rawat, Vijay Kumar, Naveen Kumar, Piyush Anand, Ravi Prakash Yadav, Somesh Baranwal, Amit Prasad, Vinod Kumar
Summary: In this study, 16 novel compounds were synthesized and evaluated for their anticancer activity. It was found that two of the compounds exhibited inhibitory effects on cancer cell proliferation and induced mitochondria-mediated apoptosis. Additionally, one of the compounds showed significant tubulin polymerization inhibition activity. Computational studies revealed that this compound had good binding affinities in the colchicine domain and thermodynamic stability. Therefore, these compounds have the potential to be developed as potent anticancer agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Marianna Bufano, Mattia Laffranchi, Silvano Sozzani, Domenico Raimondo, Romano Silvestri, Antonio Coluccia
Summary: CCRL2 is a receptor closely related to chemokine receptors, but it cannot activate G-protein signaling and induce cell migration. Its only known ligand is chemerin. CCRL2 has been shown to play a crucial role in lung dendritic cell migration, neutrophil recruitment, and natural killer cell-dependent immune surveillance in lung cancer.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Oncology
Antonio Coluccia, Marianna Bufano, Giuseppe La Regina, Michela Puxeddu, Angelo Toto, Alessio Paone, Amani Bouzidi, Giorgia Musto, Nadia Badolati, Viviana Orlando, Stefano Biagioni, Domiziana Masci, Chiara Cantatore, Roberto Cirilli, Francesca Cutruzzola, Stefano Gianni, Mariano Stornaiuolo, Romano Silvestri
Summary: The WNT/beta-catenin pathway plays a crucial role in regulating a wide range of cellular functions, and its dysregulation is closely associated with the development of cancer. In this study, the interaction between the protein Dishevelled 1 (DVL1), a key player in this pathway, and its receptor Frizzled was investigated. Through computational studies, a compound called RS4690 (1) was discovered to selectively inhibit the binding of DVL1. After separating the racemic mixture, the enantiomer (S)-1 showed better inhibition of DVL1 and the growth of HCT116 cells, indicating its potential as a new therapeutic agent against WNT-dependent colon cancer.
Review
Biochemistry & Molecular Biology
Federica Pedrucci, Claudia Pappalardo, Giovanni Marzaro, Nicola Ferri, Alberto Ferlin, Luca De Toni
Summary: PROTACs offer a promising therapeutic option for targeting specific proteins through pharmacological entities. Despite their seemingly modular design, the structure and efficacy of PROTACs require rational improvement through appropriate molecular strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Rosa Di Liddo, Marco Verona, Christian Vaccarin, Laura Acquasaliente, Sandra Schrenk, Monica Piccione, Carola Cenzi, Michele De Franco, Matteo Dal Pra, Giovanni Ribaudo, Maria Grazia Ferlin, Maria Teresa Conconi, Adriana Chilin, Valentina Gandin, Giovanni Marzaro
Summary: The study focuses on the identification of a novel class of small molecules acting on the extracellular domain of EGFR, which induced cytotoxicity in cells overexpressing EGFR and insensitive to monoclonal antibodies. These compounds have the potential to overcome KRAS-driven resistance to treatment.
Review
Pharmacology & Pharmacy
Costa Enrico, Domenica Cappellini Maria, Rivella Stefano, Chilin Adriana, Alessi Eva, Riccaboni Massimo, G. M. Leufkens Hubert, Lucio Luzzatto
Summary: Beta-thalassemia is considered a rare disease in the US and EU, and thalassemia drugs are eligible for Orphan Drug Designation. Out of the 28 granted ODDs for beta-THAL since 2001, six have become licensed drugs, indicating the contribution of ODD legislation to improved treatments for beta-THAL.
DRUG DISCOVERY TODAY
(2022)
Article
Cardiac & Cardiovascular Systems
Roberto Carnevale, Vittoria Cammisotto, Simona Bartimoccia, Cristina Nocella, Valentina Castellani, Marianna Bufano, Lorenzo Loffredo, Sebastiano Sciarretta, Giacomo Frati, Antonio Coluccia, Romano Silvestri, Giancarlo Ceccarelli, Alessandra Oliva, Mario Venditti, Francesco Pugliese, Claudio Maria Mastroianni, Ombretta Turriziani, Martina Leopizzi, Giulia D'Amati, Pasquale Pignatelli, Francesco Violi
Summary: This study identified two pathways, TLR4-dependent and independent, that promote platelet-dependent thrombus growth. It suggests that inhibiting TLR4 or p47phox could be a strategy to counteract thrombosis in SARS-CoV-2.
CIRCULATION RESEARCH
(2023)
Article
Chemistry, Medicinal
Jessica Sebastiani, Michela Puxeddu, Marianna Nalli, Ruoli Bai, Ludovica Altieri, Paola Rovella, Eugenio Gaudio, Daniela Trisciuoglio, Filippo Spriano, Patrizia Lavia, Cinzia Fionda, Domiziana Masci, Andrea Urbani, Chiara Bigogno, Giulio Dondio, Ernest Hamel, Francesco Bertoni, Romano Silvestri, Giuseppe La Regina
Summary: We synthesized a new tubulin polymerization inhibitor, RS6077, which inhibited the growth of multiple cancer cell lines without affecting non-transformed cells. It induced G2/M phase arrest in both transformed and non-transformed cells, but showed selective induction of cell death in transformed cells that fail to complete mitosis. RS6077 also inhibited the growth of a lymphoma xenograft model and demonstrated good metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Marianna Nalli, Domiziana Masci, Andrea Urbani, Giuseppe La Regina, Romano Silvestri
Summary: This review discusses the recent advances in small molecule beta-catenin agents, including the structure-activity relationships and biological activities of inhibitors, providing useful knowledge for the discovery of therapeutic beta-catenin drugs for cancer treatment.
Article
Biochemistry & Molecular Biology
Francesca Romana Mammone, Leo Zanitti, Michela Puxeddu, Giuseppe La Regina, Romano Silvestri, Anna Borioni, Roberto Cirilli
Summary: A direct and highly selective ultra-high-performance liquid chromatographic method was developed and validated for determining the content of rosuvastatin calcium salt (RSV) in medicinal products. The method achieved baseline separation of all organic related substances listed in the European Pharmacopoeia monograph for RSV tablets in less than 15 minutes. The method was proven to be linear, precise, and accurate for determining RSV and related chiral substances in tablet formulations according to the guidelines of the International Conference on Harmonization (ICH).
Article
Virology
Gilda Giancotti, Giulio Nannetti, Gilda Padalino, Martina Landini, Nanci Santos-Ferreira, Jana Van Dycke, Valentina Naccarato, Usheer Patel, Romano Silvestri, Johan Neyts, Roberto Gozalbo-Rovira, Jesus Rodriguez-Diaz, Joana Rocha-Pereira, Andrea Brancale, Salvatore Ferla, Marcella Bassetto
Summary: Human norovirus is the leading cause of foodborne diseases worldwide, resulting in severe acute gastroenteritis outbreaks and causing approximately 200,000 deaths in children in developing countries annually. Current treatment options are limited to supportive care, highlighting the urgent need for antiviral agents. In this study, we focused on the viral RNA-dependent RNA polymerase (RdRp) as a potential target for antiviral drug discovery. By rationally modifying identified scaffolds, we synthesized new compounds with improved inhibition of RdRp, providing a promising foundation for further optimization.
Article
Chemistry, Medicinal
Szabolcs Dvoracsko, Marilisa Pia Dimmito, Jessica Sebastiani, Giuseppe La Regina, Romano Silvestri, Stefano Pieretti, Azzurra Stefanucci, Csaba Tomboly, Adriano Mollica
Summary: In this study, 1H-pyrazole-3-carboxylic acids related to the CB1 receptor antagonist rimonabant were modified and tested for their activities on CB1 receptors. Compound 34 exhibited strong binding affinity and agonist activity towards CB1 receptors. In vivo experiments showed its potential analgesic effect and food intake-increasing activity.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
Marianna Bufano, Michela Puxeddu, Marianna Nalli, Giuseppe La Regina, Angelo Toto, Francesca Romana Liberati, Alessio Paone, Francesca Cutruzzol, Domiziana Masci, Chiara Bigogno, Giulio Dondio, Romano Silvestri, Stefano Gianni, Antonio Coluccia
Summary: Growth factor receptor bound protein 2 (Grb2) is an adaptor protein that regulates important cellular pathways. It is found overexpressed in many tumor types and is a target for anticancer drug development. In this study, a series of Grb2 inhibitors were synthesized and evaluated. Five of the synthesized derivatives showed promising inhibitory concentration in cancer cells. The most active compound, derivative 12, showed inhibitory concentrations for different cancer cells and its metabolic stability and ROS production were evaluated. The biological data and docking studies provided insights into the structure-activity relationship.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Marianna Nalli, Laura Di Magno, Yichao Wen, Xin Liu, Michele D'Ambrosio, Michela Puxeddu, Anastasia Parisi, Jessica Sebastiani, Andrea Urbani, Antonio Coluccia, Silvia Ripa, Fiorella Di Pastena, Davide Capelli, Roberta Montanari, Domiziana Masci, Andrea Urbani, Chiara Bigogno, Claudio Sette, Viviana Orlando, Sara D'Angelo, Stefano Biagioni, Chiara Bigogno, Giulio Dondio, Arianna Pastore, Mariano Stornaiuolo, Gianluca Canettieri, Te Liu, Romano Silvestri, Giuseppe La Regina
Summary: Novel N-(heterocyclylphenyl)benzenesulfonamides were synthesized and showed strong inhibition of luciferase activity. Compound 9 inhibited the growth of TNBC cells and induced cell death in colorectal cancer cells. Compound 9 disrupted the association between beta-catenin and Tcf-4, and shared a common binding site with Tcf-4 in the hotspot binding region. These findings highlight the potential of this novel class of beta-catenin inhibitors as anticancer agents.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
