Article
Biochemistry & Molecular Biology
Bing Yang, Jiahua Zhou, Fa Wang, Xiao-Wei Hu, Yujun Shi
Summary: In this study, a series of pyrazoline derivatives bearing 3,4,5-trimethoxy phenyl and thiophene moieties were synthesized and evaluated as tubulin polymerization inhibitors. The top hit compound, 3q, showed potent anti-proliferation activity on cancer cell lines and comparable efficacy with less toxicity than the positive control Colchicine. Further investigations indicated the potential for improving tubulin polymerization inhibition and introducing VEGFR2 inhibition through ring transposition.
BIOORGANIC 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)
Review
Chemistry, Multidisciplinary
Chao Wang, Jing Chang, Shanbo Yang, Lingyu Shi, Yujing Zhang, Wenjing Liu, Jingsen Meng, Jun Zeng, Renshuai Zhang, Dongming Xing
Summary: This article reviews the research progress of novel CA-4 containing quinoline analogs in anti-tumor from 1992 to 2022 and expounds on the pharmacological mechanisms of these effective compounds, including but not limited to apoptosis, cell cycle, tubulin polymerization inhibition, immune Fluorescence experiments, etc., which lay the foundation for the subsequent development of CA-4 containing quinoline analogs for clinical use.
FRONTIERS IN CHEMISTRY
(2022)
Article
Oncology
Clayton J. Bell, Kyle G. Potts, Mary M. Hitt, Desmond Pink, Jack A. Tuszynski, John D. Lewis
Summary: The novel colchicine derivative CR42-24 has shown selective cytotoxicity against various cancer cell lines, with high activity in bladder cancer cell lines. Monotherapy with CR42-24 in an aggressive urothelial carcinoma xenograft model effectively controls large tumors. The combination of CR42-24 with standard chemotherapies gemcitabine and cisplatin demonstrates high synergistic effects, increasing its potential as a novel treatment for urothelial carcinoma.
Article
Pharmacology & Pharmacy
Yan-Bo Zheng, Yan-Qun Dong, Shu-Yi Si, Yong-Su Zhen, Jian-Hua Gong
Summary: IMB5476, a novel nitrobenzoate microtubule inhibitor, exhibits increased aqueous solubility. It disrupts microtubule networks in cells, causing cell cycle arrest and inducing cell death through mitotic catastrophe and apoptosis. IMB5476 also inhibits angiogenesis and overcomes multidrug resistance.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ganesh Pai Bellare, Birija Sankar Patro
Summary: This study proposes the usage of resveratrol as a chemosensitizer in combination with talazoparib for targeting HR proficient breast cancers. Resveratrol effectively enhances talazoparib-induced cell death in breast cancer cells and shows minimal cytotoxicity in normal cells.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Ruo-Jun Man, Tian Lu, Chi-Chong Zheng, Tong Li, Meng-Ke Wu, Dong-Dong Li, Xue-Mei He
Summary: In this study, a series of indole-containing pyrazole-carbohydrazide derivatives were synthesized and evaluated for their biological activity. Among them, compound A18 showed notable antiproliferative and microtubule polymerization inhibitory activities, with lower cytotoxicity. Cell scratch test and confocal imaging demonstrated the potential of A18 in blocking cell migration and inducing mitotic catastrophe.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Anastazja Poczta, Piotr Krzeczynski, Maksim Ionov, Aneta Rogalska, Udo S. Gaipl, Agnieszka Marczak, Dorota Lubgan
Summary: This study synthesized a series of new derivatives by modifying the molecular structure of melphalan, and proved that EM-MOR-MEL and EM-T-MEL have better anti-cancer activity. These derivatives achieve their effects on multiple myeloma cells by affecting DNA conformation, increasing DNA damage, arresting cell cycle, and activating mitotic catastrophe.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Xiang-Yu Yan, Jia-Fu Leng, Ting-Ting Chen, Yong-Jun Zhao, Ling-Yi Kong, Yong Yin
Summary: A series of novel diphenylamine derivatives were synthesized and evaluated for their anti-proliferative activities against human cancer cell lines. Among them, compound 5f exhibited promising anti-proliferative activity against HT29 cells and showed inhibitory effects on cancer cell migration, colony formation, and angiogenesis. Further studies revealed that compound 5f inhibited tubulin polymerization, arrested HT29 cell cycle, induced cell apoptosis, and inhibited tumor growth in animal models. The compound also demonstrated good pharmacokinetic properties. These findings suggest that compound 5f has potential as an antitumor candidate and warrants further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lin Chen, Bei Zhang, Yan-Hong Li, Xian-Sen Huo, Wen-Wei You, Pei-Liang Zhao
Summary: Based on previous work, a series of novel triazolylthioacetones incorporating various fragments were synthesized and evaluated for their anticancer activities and interaction with tubulin. Some of the compounds showed potent activity, with compound IIc exhibiting promising results against multiple tumor cell lines. Mechanistic studies revealed that IIc could cause cell cycle arrest and inhibit tubulin polymerization. Molecular docking analysis suggested that IIc could bind to the colchicine-binding site, similar to other tubulin polymerization inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Viharika Bobba, Yaxin Li, Marjia Afrin, Raina Dano, Wenjing Zhang, Bibo Li, Bin Su
Summary: Researchers have developed a selective drug candidate library for the treatment of Human African trypanosomiasis. One compound in particular has shown high potency and selectively inhibits the growth of trypanosome cells. Further studies will guide future optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shannon Pecnard, Olivier Provot, Helene Levaique, Jerome Bignon, Laurie Askenatzis, Francois Saller, Delphine Borgel, Sophie Michallet, Marie-Catherine Laisne, Laurence Lafanechere, Mouad Alami, Abdallah Hamze
Summary: A series of cyclic bridged analogs of isocombretastatin A-4 with compound 42 showed high antiproliferative activity against a panel of cancer cell lines, as well as strong activity against colon-carcinoma cells and MDR1-overexpressing K562R cell line. Compound 42 also effectively inhibited tubulin polymerization, induced cell cycle arrest, and caused caspase-induced apoptosis in K562 cells. Additionally, compound 42 was significantly less cytotoxic in non-cancer cells compared to isoCA-4.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Toxicology
Ryota Tochinai, Yoshiyasu Nagashima, Shin-ichi Sekizawa, Masayoshi Kuwahara
Summary: Microtubule polymerization inhibitors (MPIs) are used as anticancer agents and have potential applications in both human and veterinary fields. However, they carry a risk of cardiotoxicity. This paper reviews the pharmacological effects and cardiotoxicity mechanisms of MPIs, and suggests potential strategies to minimize cardiotoxicity, such as blood pressure control and combined administration with other anticancer agents. Monitoring cardiotoxicity using myocardial injury markers and echocardiography, particularly two-dimensional speckle tracking, can help in early detection of MPI-induced cardiac dysfunction. Understanding the toxicity of MPIs and exploring their potential will contribute to the further development of cancer chemotherapy.
JOURNAL OF APPLIED TOXICOLOGY
(2023)
Article
Chemistry, Physical
Mohammed Hawash, Sezen Guntekin Ergun, Deniz Cansen Kahraman, Abdurrahman Olgac, Ernest Hamel, Rengul Cetin-Atalay, Sultan Nacak Baytas
Summary: Structurally diverse indole-3-pyrazole-5-carboxamide analogues were synthesized and evaluated for antiproliferative activity against three cancer cell lines. Some derivatives showed comparable or better anticancer activities than sorafenib. Compound 18 exhibited potent activity against hepatocellular cancer cell lines and also showed moderate inhibitory activity against tubulin polymerization. Docking simulations and quantum mechanical calculations were performed to elucidate the interaction and electronic nature of compound 18.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Joshua Thammathong, Kaylee B. Chisam, Garrett E. Tessmer, Carl B. Womack, Mario M. Sidrak, April M. Weissmiller, Souvik Banerjee
Summary: Targeting the colchicine binding site on tubulin is a promising approach for cancer treatment. However, balancing metabolic stability and cellular potency of new colchicine binding site inhibitors (CBSIs) remains an issue that needs to be resolved.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Correction
Biochemistry & Molecular Biology
Mohamed Marzouk, Shimaa M. Khalifa, Amal H. Ahmed, Ahmed M. Metwaly, Hala Sh. Mohammed, Hanan A. A. Taie
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Yong-Si Liu, Ming-Hao Hu
Summary: In this study, a selffolded fluorescent probe was designed to selectively illuminate G4s by unfolding its intramolecular aggregation mediated by G4 binding. This probe showed more controllable background emission and promising ability to track G4 forming dynamics compared to previous disaggregation-induced emission (DIE) probes.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Xiang, Zhuo Yuan, Qichuan Deng, Linshen Xie, Dongke Yu, Jianyou Shi
Summary: This review provides a brief description of the diagnosis, pathogenesis, and potential therapeutic inhibitors for renal fibrosis. Currently, there are no clear therapeutic targets or drugs for renal fibrosis; however, some natural products may have potential efficacy for treating renal fibrosis.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Simone Giovannuzzi, Anna Nikitjuka, Bruna Rafaela Pereira Resende, Michael Smietana, Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Summary: Boron-based compounds have been extensively studied in medicinal chemistry, playing a crucial role in designing small molecule drugs for various diseases. Boron is particularly valuable in developing inhibitors for metalloenzymes carbonic anhydrases, and it can modulate ligand recognition ability and selectivity. Recent advancements have led to the discovery of novel boron-based inhibitors that can inhibit carbonic anhydrases through a Lewis acid-base mechanism. Further research is needed to fully explore the potential of boron-based inhibitors and advance their clinical applications.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Xinxin Liu, Lei Chen, Ze Chen
Summary: This study developed a nanostructured photosensitizer loaded with oxygen-throttling drug and demonstrated its enhanced cytotoxicity against tumor cells under hypoxic conditions. Animal experiments showed the enhanced tumor targeting capability of the photosensitizer and its inhibitory effect on tumor growth.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Shuai Jiang, Wen-Yan Li, Zai-Feng Yuan, Qin-Shi Zhao
Summary: This study isolated two new dimeric Lycopodium alkaloids and twelve previously undescribed Lycopodium alkaloids from Lycopodiastrum casuarinoides. The structures of these compounds were determined and their inhibitory activities on the Cav3.1 channel were evaluated.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yan Yang, Dong-Xiao Yan, Rui-Xue Rong, Bing-Ye Shi, Man Zhang, Jing Liu, Jie Xin, Tao Xu, Wen-Jie Ma, Xiao-Liu Li, Ke-Rang Wang
Summary: In this study, a series of nucleolar fluorescent probes based on naphthalimide derivatives were designed and synthesized, which could achieve clear nucleolar staining in living cells. The results showed that these probes exhibited good targeting to the cell nucleolus and could bind to RNA and enhance fluorescence. This has positive implications for the diagnosis and treatment of nucleolus-related diseases.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yongxi Dong, Fang Wang, Jinlan Wen, Yongqing Mao, Shanhui Zhang, Tiemei Long, Zhangxiang Yang, Lei Li, Jiquan Zhang, Li Dong, Gang Liu, Jianwei Xu
Summary: The hybrid molecules of Scutellarein and Tertramethylpyrazine show excellent neuroprotective and antiplatelet effects in the treatment of ischemic stroke. Compound 1e is particularly effective, enhancing cell membrane permeability and inhibiting cell uptake, as well as significantly reducing cerebral infarction volume.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Yu Chen, Yuanyuan Ying, Jonathan Lalsiamthara, Yuheng Zhao, Saber Imani, Xin Li, Sijing Liu, Qingjing Wang
Summary: This paper examines the role and metabolic regulation of NAD+ in bacteria, highlighting its impact on physiology and virulence. It explores enzymes associated with NAD+ metabolism as potential targets for antibacterial drugs and vaccine candidates. Additionally, it scrutinizes the medical potential of NAD+ and provides insights for its application in biomedicine.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Jon Macicior, Daniel Fernandez, Silvia Ortega-Gutierrez
Summary: Hutchinson-Gilford progeria syndrome (HGPS), also known as progeria, is a rare genetic disease that causes premature aging and significantly reduces life expectancy. Currently, there is only one approved drug for treating progeria, but its efficacy is limited. Progerin levels are believed to be the most important biomarker related to disease severity.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Fuko Hirano, Naoya Kondo, Yusuke Murata, Aya Sudani, Takashi Temma
Summary: Fluorinated alpha-methyl 3BPA derivatives showed improved water solubility, tumor targetability, and biodistribution compared to 3BPA and BPA, resulting in significantly improved tumor-to-normal tissue ratios.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Ying Shi, Jiaqin Tang, Shumeng Zhi, Ruiqi Jiang, Qing Huang, Lei Sun, Zhizhong Wang, Yanran Wu
Summary: Necroptosis is a type of cell death associated with various diseases. In this study, we identified a small molecule inhibitor, SY-1, that effectively blocks necroptosis by inhibiting the phosphorylation of RIP1/RIP3/MLKL pathway. SY-1 also showed protective effects against TNF-induced hypothermia and improved survival in mice with SIRS. These findings highlight the potential therapeutic applications of SY-1.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Andrea Bagan, Sonia Abas, Judith Pala-Pujadas, Alba Irisarri, Christian Grinan-Ferre, Merce Pallas, Itziar Muneta-Arrate, Carolina Muguruza, Luis F. Callado, Belen Perez, Elies Molins, Jose A. Morales-Garcia, Carmen Escolano
Summary: Recent studies have identified the modulation of imidazoline I-2 receptors (I-2-IR) by selective ligands as a potential strategy for treating neurodegenerative diseases. This study reports a family of bicyclic alpha-iminophosphonates that show high affinity and selectivity for I-2-IR and demonstrates their neuroprotective and anti-inflammatory effects in in vitro and in vivo models. The findings emphasize the importance of exploring structurally novel I-2-IR ligands for therapeutic strategies in neurodegeneration.
BIOORGANIC CHEMISTRY
(2024)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)