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
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
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)
Article
Chemistry, Multidisciplinary
Heba M. Abosalim, Manal A. Nael, Tarek F. El-Moselhy
Summary: Twenty derivatives of chalcones were synthesized and evaluated for their anticancer activities, with five compounds showing broad antitumor activity against breast and liver cancer cell lines. Compound 3 h exhibited the most powerful anticancer activity and effective inhibition on tubulin, with low toxicity towards normal human cell lines. The docking study revealed that 3 h had the best binding mode among all the derivatives.
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, Multidisciplinary
Lingyu Shi, Shanbo Yang, Jing Chang, Yujing Zhang, Wenjing Liu, Jun Zeng, Jingsen Meng, Renshuai Zhang, Chao Wang, Dongming Xing
Summary: A series of new compounds were synthesized and evaluated for their antitumor activity as tubulin polymerization inhibitors. Compound 7k showed the strongest anti-proliferative activity and could block the cell cycle and induce apoptosis.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yilin Fang, Zhilin Wu, Mengwu Xiao, Li Wei, Kangming Li, Yuting Tang, Jiao Ye, Jiannan Xiang, Aixi Hu
Summary: Novel 2-oxoquinoline derivatives containing arylaminothiazole, specifically compound A7, showed potent cytotoxic activity against various cancer cell lines in vitro. Compound A7 inhibits tubulin polymerization, induces cell cycle arrest, apoptosis, and mitochondrial depolarization in HeLa cells, making it a promising lead for the development of microtubule polymerization inhibitors for cancer therapy.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Momen R. Fareed, Mai E. Shoman, Mohammed I. A. Hamed, Mohamed Badr, Hanin A. Bogari, Sameh S. Elhady, Tarek S. Ibrahim, Gamal El-Din A. Abuo-Rahma, Taha F. S. Ali
Summary: A series of 3-benzylideneindolin-2-one compounds were designed and synthesized based on the structures of combretastatin A-4 and compound IC261. These compounds showed significant growth inhibition against PC-3, MCF-7 and COLO-205 cells, with some exhibiting potent activity against COLO-205 with IC50 values of 0.2 and 0.3 mu M. Mechanistic studies demonstrated their efficacy in inhibiting microtubule assembly, CK1, and EGFR, inducing apoptosis and dysregulating apoptotic markers. These compounds are considered promising multitarget agents against colon cancer.
Article
Chemistry, Medicinal
Julia Krzywik, Maral Aminpour, Jan Janczak, Ewa Maj, Mahshad Moshari, Witold Mozga, Joanna Wietrzyk, Jack A. Tuszynski, Adam Huczynski
Summary: Colchicine and its derivatives exhibit high cytotoxicity against cancer cells, with their mode of action believed to involve binding to the colchicine site at the molecular level.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Md Jahangir Alam, Ozair Alam, Ahmad Perwez, Moshahid Alam Rizvi, Mohd Javed Naim, Vegi Naidu, Mohd Imran, Mohammed M. Ghoneim, Sultan Alshehri, Faiyaz Shakeel
Summary: In this study, a series of compounds were designed, synthesized, and evaluated for their anti-cancer activity and cytotoxicity. Compound 5o showed excellent cytotoxicity and most of the compounds exhibited drug-like properties.
Article
Biochemistry & Molecular Biology
Dilipkumar Pal, In-ho Song, Shrikant Dashrath Warkad, Keum-soo Song, Gyu Seong Yeom, Supriyo Saha, Pramod B. Shinde, Satish Balasaheb Nimse
Summary: This review presents the research advances on compounds containing indazole scaffolds as microtubule targeting agents based on articles published in the last two decades. Several compounds have shown potent microtubule inhibition and anticancer activity, with some of them having the lowest IC50 values observed in cell line studies.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jing Li, Ru Si, Qingqing Zhang, Yanchen Li, Jie Zhang, Yuanyuan Shan
Summary: Based on the scaffold hybridization strategy, twenty-four indole-guanidines were designed and synthesized. Most of these hybrids exhibited moderate to high anti-proliferative activity against various cancer cells, especially human hepatoma cell lines. Selectivity investigation showed that the hybrids had the best selectivity for the SMMC-7721 subtype in human hepatoma cells. Particularly, compound 22 demonstrated potent inhibition against SMMC-7721 cells, inducing apoptosis and cell cycle arrest in a dose-dependent manner, while down-regulating the expression of specific proteins.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
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)
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)
Review
Chemistry, Medicinal
Mudasir Nabi Peerzada, Mohammad Sultan Dar, Saurabh Verma
Summary: Tubulin is a promising target for drug discovery, and compounds binding in the colchicine site could be significant in overcoming drug resistance. The development of antibody drug conjugates (ADCs) for tubulin polymerization inhibition may be an important strategy for cancer treatment.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)