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
Chemistry, Medicinal
Shannon Pecnard, Abdallah Hamze, Jerome Bignon, Bastien Prost, Alain Deroussent, Laura Gallego-Yerga, Rafael Pelaez, Ji Yeon Paik, Marc Diederich, Mouad Alami, Olivier Provot
Summary: In this study, various ligands related to Combretastatin A-4 and isoCombretastatin A-4 were designed, synthesized, and evaluated for their ability to inhibit tubulin polymerization. The lead compound 15d showed remarkable sub-nanomolar cytotoxicity against 9 human cancer cell lines, with an IC50 value below 1 nM.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yu Hong, Yuan-Yuan Zhu, Qiuqin He, Shuang-Xi Gu
Summary: This review summarizes the recent progress in the development of indole derivatives as tubulin polymerization inhibitors from 2010 to present. It provides useful clues and inspirations for the further design of outstanding inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Ashima Dhiman, Rupam Sharma, Rajesh K. Singh
Summary: Cancer, the second leading cause of death after heart disease, is characterized by the uncontrolled growth of cells. Targeting specific genes and proteins involved in the growth and survival of cancer cells has become a top priority in global research. Indole moiety, a combination of aromatic-heterocyclic compounds, has emerged as a promising scaffold for the development of anticancer drugs due to its bioavailability, unique chemical properties, and significant pharmacological behaviors. Recent advances in the medicinal chemistry of indole derivatives, including the synthesis of potential anticancer compounds and their mechanism of action, are discussed in this review.
ACTA PHARMACEUTICA SINICA B
(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)
Review
Oncology
Neha Devi, Kamalpreet Kaur, Avadh Biharee, Vikas Jaitak
Summary: Indole derivatives as anti-cancer agents have multiple mechanisms of action and show promising anti-cancer potential, including inducing apoptosis, inhibiting estrogen receptor, and inhibiting tyrosine kinase. Studies have shown that indole derivatives exhibit significant activity against cancer cell lines.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Zuzanna Rzepka, Ewa Bebenek, Elwira Chrobak, Dorota Wrzesniok
Summary: The synthesized new 28-indole-betulin derivatives showed promising anticancer activity, particularly against MCF-7 breast cancer cells, possibly through inducing apoptosis.
Article
Biochemistry & Molecular Biology
Guangcheng Wang, Wenjing Liu, Meiyan Fan, Min He, Yongjun Li, Zhiyun Peng
Summary: A novel series of thiazole-naphthalene derivatives were designed, synthesised, and evaluated for their anti-proliferative activities. Among them, compound 5b showed the highest activity as a tubulin polymerisation inhibitor, inducing apoptosis in cancer cells by arresting the cell cycle at G2/M phase.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Kotaro Yamamoto, Dagny Grzech, Konstantinos Koudounas, Emily Amor Stander, Lorenzo Caputi, Tetsuro Mimura, Vincent Courdavault, Sarah E. O'Connor
Summary: Researchers developed an improved VIGS method and discovered a new biosynthetic enzyme, serpentine synthase (SS), in Catharanthus roseus, which produces beta-carboline alkaloids with strong blue autofluorescence and potential pharmacological activity.
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
Biochemistry & Molecular Biology
Rungroj Saruengkhanphasit, Chutikarn Butkinaree, Narittira Ornnork, Kriengsak Lirdprapamongkol, Worawat Niwetmarin, Jisnuson Svasti, Somsak Ruchirawat, Chatchakorn Eurtivong
Summary: Utilizing three different virtual screening techniques, eight new derivatives of 3-phenyl-1H-indole-2-carbohydrazide with antiproliferative activities were identified; among them, 27a exhibited the most potent tubulin inhibitory activity and induced G2/M phase arrest. Derivatives 27b, 27d, and 27i showed strong activities against various cell lines, with bromine substitution at R1 position demonstrating the most prominent anticancer effects.
BIOORGANIC CHEMISTRY
(2021)
Article
Plant Sciences
Wei Yan, Yong Li, Yan Liu, Yi Wen, Heying Pei, Jianhong Yang, Lijuan Chen
Summary: In this study, the binding interaction between the isoflavone compound barbigerone and tubulin protein was investigated. The crystal structure of the tubulin-barbigerone complex was solved, revealing the binding site and mode of barbigerone. A more active isoflavone derivative, 0412, was synthesized based on this structure. Both barbigerone and 0412 exhibited anticancer activities by inhibiting tubulin polymerization, cell proliferation, migration, and inducing cell cycle arrest and apoptosis.
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.
Article
Chemistry, Organic
Xu-Yang Hu, Hai-Feng Xu, Qiang Chen, You-Lu Pan, Jian-Zhong Chen
Summary: In this study, a novel synthesis method was developed for the indolo[2,1-alpha]isoquinoline core structure under air environment, resulting in the successful synthesis of various valuable derivatives with good yields. A radical pathway was proposed to explain the experimental results.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Physical
T. Shreedhar Reddy, Sanjay Rai, Shiva Kumar Koppula
Summary: Herein, the synthesis of indole-tetrazole coupled aromatic amides and their in vitro anticancer activity were described. Several compounds showed higher activity than the standard drug against human cancer cell lines, and they exhibited double potency in inhibiting tubulin polymerization. Molecular docking studies indicated good binding interactions between these compounds and the target protein. In silico ADMET studies further confirmed the drug-likeness of the potent compounds.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Organic
Nathanyal J. Truax, Fernando Banales Mejia, Deborah O. Kwansare, Megan M. Lafferty, Maeve H. Kean, Erin T. Pelkey
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Chemistry, Organic
Fernando Banales Mejia, Megan M. Lafferty, Sophia J. Melvin, Nathanyal J. Truax, Maeve H. Kean, Erin T. Pelkey
Article
Chemistry, Organic
Sarah J. P. Yoon-Miller, Kathryn M. Dorward, Kimberly P. White, Erin T. Pelkey
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2009)
Article
Chemistry, Organic
Jessica G. Greger, Sarah J. P. Yoon-Miller, Nathan R. Bechtold, Scott A. Flewelling, Jacob P. MacDonald, Catherine R. Downey, Eric A. Cohen, Erin T. Pelkey
JOURNAL OF ORGANIC CHEMISTRY
(2011)
Article
Chemistry, Organic
Amy A. van Loon, Maeve K. Holton, Catherine R. Downey, Taryn M. White, Carly E. Rolph, Stephen R. Bruening, Guanqun Li, Katherine M. Delaney, Sarah J. Pelkey, Erin T. Pelkey
JOURNAL OF ORGANIC CHEMISTRY
(2014)
Meeting Abstract
Biochemistry & Molecular Biology
Grace Faulkner, Erin Pelkey
Article
Chemistry, Organic
Christian A. Moore, Brian F. Ohman, Matthew J. Garman, Michael E. Liquori, David M. Degan, Kailey B. Voellinger, Michael J. DePersis, Erin T. Pelkey
Article
Chemistry, Medicinal
Patricia Mowery, Fernando Banales Mejia, Courtney L. Franceschi, Maeve H. Kean, Deborah O. Kwansare, Megan M. Lafferty, Namita D. Neerukonda, Carly E. Rolph, Nathanyal J. Truax, Erin T. Pelkey
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2017)
Article
Chemistry, Organic
Kathryn M. Dorward, Nicolette J. Guthrie, Erin T. Pelkey
SYNTHESIS-STUTTGART
(2007)
Article
Chemistry, Organic
Sarah J. P. Yoon-Miller, Suzanne M. Opalka, Erin T. Pelkey
TETRAHEDRON LETTERS
(2007)
Article
Chemistry, Organic
Aaron R. Coffin, Michael A. Roussell, Elina Tserlin, Erin T. Pelkey
JOURNAL OF ORGANIC CHEMISTRY
(2006)
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)
