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, Multidisciplinary
Bharat Goel, Biswajit Dey, Essha Chatterjee, Nancy Tripathi, Nivedita Bhardwaj, Sanjay Kumar, Santosh Kumar Guru, Shreyans K. Jain
Summary: In this study, gloriosine and other compounds were isolated from Gloriosa superba roots and evaluated for their antiproliferative activities against various cancer cell lines. Gloriosine showed significant selective anticancer activity, inducing apoptosis and inhibiting cell migration.
Review
Chemistry, Medicinal
Bharat Goel, Shivani Jaiswal, Shreyans K. K. Jain
Summary: Microtubules are important intracellular targets for anticancer activity. Various drugs, such as paclitaxel and vinblastine, act by altering the dynamics of microtubules. In this study, the potential of indole derivatives as colchicine-binding site inhibitors is reviewed. These derivatives have shown the ability to inhibit cancer cell proliferation, induce apoptosis, and disrupt microtubule formation. Understanding the structure-activity relationship of these compounds could lead to the development of novel and effective cancer therapies.
ARCHIV DER PHARMAZIE
(2023)
Article
Oncology
Raisa Krutilina, Kelli L. Hartman, Damilola Oluwalana, Hilaire C. Playa, Deanna N. Parke, Hao Chen, Duane D. Miller, Wei Li, Tiffany N. Seagroves
Summary: The study demonstrates the effectiveness of sabizabulin in inhibiting the growth and migration of HER2+ breast cancer cells, and inducing cell death. Sabizabulin is a promising alternative to taxanes for the treatment of HER2+ breast cancer, with similar anti-metastatic efficacy but better oral bioavailability and lower toxicity.
Review
Pharmacology & Pharmacy
Jiaxing Wang, Duane D. Miller, Wei Li
Summary: This review summarizes the crystal structures of tubulin in complexes with various CBSIs, aiming to facilitate the discovery of new generations of tubulin inhibitors.
DRUG DISCOVERY TODAY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Felipe Montecinos, Dan L. Sackett
Summary: Microtubule-targeting agents (MTAs) bind to specific sites in the subunit of microtubules. The colchicine binding site (CBS) is a common target for drugs to treat human diseases and parasitic infections. However, despite the diversity of tubulin sequences and the molecules that bind to CBS, there is currently no pattern to predict the affinity of new molecules. This commentary discusses the varying binding affinities of drugs that bind to CBS and explores structural data explaining experimental differences.
Article
Biochemistry & Molecular Biology
Shanbo Yang, Chao Wang, Lingyu Shi, Jing Chang, Yujing Zhang, Jingsen Meng, Wenjing Liu, Jun Zeng, Renshuai Zhang, Yingchun Shao, Dongming Xing
Summary: A set of novel diarylpyridines as anti-tubulin agents were designed and synthesised, among which compound 10t showed remarkable antiproliferative activities and disrupted the cellular microtubule structure, arrested cell cycle and induced apoptosis.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ibrahim H. Eissa, Mohammed A. Dahab, Mohamed K. Ibrahim, Nawaf A. Alsaif, A. Z. Alanazi, Sally Eissa, Ahmed B. M. Mehany, Andre M. Beauchemin
Summary: Thirty-five new colchicine binding site inhibitors were designed and synthesized based on the 1,2,4-triazin3(2H)-one nucleus. Two compounds showed significant antiproliferative effects against three human cancer cell lines, and further investigation revealed their potential as tubulin polymerization inhibitors. The synthesized compounds demonstrated selectivity against cancer cells and upregulated levels of active caspase-3 and pro-apoptotic protein Bax, suggesting their potential as anti-cancer agents. Additionally, in silico studies showed promising interactions with the colchicine binding site and favorable pharmacokinetic properties.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Laura Gallego-Yerga, Andrea Jazmin Chiliquinga, Rafael Pelaez
Summary: Increasing awareness of the structure of microtubules has driven research on targeting tubulin for novel chemotherapies, particularly for glioblastoma multiforme (GBM) cells. Optimization of potently anti-tubulin drugs with improved pharmacokinetic properties is challenging, but the use of ensemble pharmacophore screening has led to the development of a new tetrazole-based tubulin inhibitor. This inhibitor demonstrated remarkable antimitotic effects against various cancer cells, especially GBM cells, with high selectivity and overcome the limitations typically associated with tubulin binding agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mohamed Hagras, Moshira A. El Deeb, Heba S. A. Elzahabi, Eslam B. Elkaeed, Ahmed B. M. Mehany, Ibrahim H. Eissa
Summary: Newly synthesized quinoline derivatives exhibited superior cytotoxic activities and inhibitory effects against tubulin polymerisation in human cancer cell lines, potentially serving as promising anticancer agents.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Wei Liu, Youyou He, Zhongjie Guo, Miaomiao Wang, Xiaodong Han, Hairui Jia, Jin He, Shanshan Miao, Shengzheng Wang
Summary: The study aimed to design and optimize analogues of 2-aryl-4-amide-quinoline derivatives targeting the colchicine binding site of tubulin. Analogues C1 similar to J2 were obtained with diverse substituents and scaffolds. Among them, G13 analogue with a hydroxymethyl group exhibited good tubulin polymerisation inhibitory activity (IC50 = 13.5 μM) and potent antiproliferative activity (IC50 values: 0.65 μM to 0.90 μM). G13 effectively inhibited migration, invasion, and angiogenesis of MDA-MB-231 cells, and induced intracellular ROS increase, MMP decrease, and microtubule network fragmentation and disassembly. Moreover, G13 demonstrated significant in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Wolfgang Dohle, Hannah Asiki, Wojciech Gruchot, Paul A. Foster, Havreen K. Sahota, Ruoli Bai, Kirsten E. Christensen, Ernest Hamel, Barry V. L. Potter
Summary: 2-Difluoromethoxyestratriene derivatives were designed to improve the potency and stability of the drug candidate 2-methoxyestradiol (2ME2). Evaluation showed that these compounds exhibit promising anti-cancer activity and significant inhibition of steroid sulfatase and tubulin.
Article
Cell Biology
Felipe Montecinos, Maura Loew, Tak I. Chio, Susan L. Bane, Dan L. Sackett
Summary: This study aimed to explore the structure-activity relationship of colchicine site in chicken erythrocyte tubulin and found that benzimidazole class ligands have increased affinity for this divergent isotype.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Physical
Ashish Ranjan Dwivedi, Vijay Kumar, Ravi Prakash Yadav, Naveen Kumar, Kailash Jangid, Piyush Anand, Deepak Kumar Sharma, Somesh Barnawal, Vinod Kumar
Summary: A series of 4-Phenyl-1,2,3-triazole substituted pyrimidine derivatives were synthesized and evaluated for their anti-proliferative and anti-tubulin activities. AV-6 and AV-14 exhibited activity against three cancer cell lines, with IC50 values ranging from 1.2μM to 5.5μM for AV-6 and from 4.7μM to 1.4μM for AV-14. These compounds showed non-toxicity to normal cells and induced mitochondria-mediated apoptosis. AV-6 displayed significant tubulin polymerization inhibition potential.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Wei Liu, Hairui Jia, Minghao Guan, Minxuan Cui, Zhuxuan Lan, Youyou He, Zhongjie Guo, Ru Jiang, Guoqiang Dong, Shengzheng Wang
Summary: In this study, a novel tubulin inhibitor E27 was discovered through structural optimization. E27 demonstrated significant antitumor activity, inhibition of cancer cell migration, induction of apoptosis, and cell cycle arrest.
BIOORGANIC CHEMISTRY
(2022)