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
Gang Li, Jia-Qiang Wu, Xiaojia Cai, Wen Guan, Zhijun Zeng, Yanghui Ou, Xiaoyun Wu, Jiayu Li, Xiangxiang Fang, Jinling Liu, Yali Zhang, Huamin Wang, Canqiang Yin, Hongliang Yao
Summary: A series of diaryl heterocyclic analogues were synthesized as tubulin polymerization inhibitors. Compound 6y exhibited the highest antiproliferative activity against HCT-116 colon cancer cells and effectively inhibited tubulin polymerization in vitro. It also showed high metabolic stability on human liver microsomes and suppressed tumor growth in a HCT-116 mouse colon model without toxicity. These results suggest that 6y represents a new class of tubulin inhibitors worthy of further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
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
Chemistry, Medicinal
Jian Song, Yong-Feng Guan, Wen-Bo Liu, Chun-Hong Song, Xin-Yi Tian, Ting Zhu, Xiang-Jing Fu, Ying-Qiu Qi, Sai-Yang Zhang
Summary: This study designed, synthesized, and evaluated novel coumarin-indole derivatives as tubulin polymerization inhibitors targeting the colchicine binding site. Compound MY-413 showed potent inhibitory activities against gastric cancer cells, inhibited tubulin polymerization, and MAPK signaling pathway, induced cell apoptosis and proliferation inhibition both in vitro and in vivo. In addition, MY-413 significantly inhibited tumor growth in xenograft tumor models without obvious toxicity. Overall, MY-413 is a promising lead compound for further investigation as a potential anti-gastric cancer agent.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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)
Article
Chemistry, Medicinal
Naglaa F. El-Sayed, Marwa El-Hussieny, Ewies F. Ewies, Mohamed F. El Shehry, Hanem M. Awad, Marwa A. Fouad
Summary: Microtubules and the mitotic spindle are crucial targets for cancer treatment, and benzofuran and indole derivatives were designed as tubulin polymerization inhibitors in this study. Compound 6a showed strong antiproliferative activity by inhibiting tubulin polymerization and disrupting mitotic spindle formation, leading to apoptosis of HepG2 cells. It fit properly at the colchicine binding site of tubulin, suggesting it as a promising anticancer candidate for liver and breast cell carcinoma treatment.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Magdalena Peruzynska, Aleksandra Borzyszkowska-Ledwig, Jacek G. Sosnicki, Lukasz Struk, Tomasz J. Idzik, Gabriela Maciejewska, Lukasz Skalski, Katarzyna Piotrowska, Pawel Lukasik, Marek Drozdzik, Mateusz Kurzawski
Summary: This study successfully obtained a mitotic-specific inhibitor with high antiproliferative activity and selectivity through structural modifications. By inhibiting tubulin polymerization in a dose-dependent manner, aberrant mitotic spindle formation was induced, leading to cell cycle arrest and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Mayank, Ashutosh Singh, Kumar Udit Saumya, Mayank Joshi, Navneet Kaur, Neha Garg, Narinder Singh
Summary: 4H-Chromene derivatives are potential anticancer compounds that bind to the colchicine binding site of tubulin protein. The 2-amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile-based 4H-chromenes scaffold has a significant impact on tubulin proteins. Understanding the interaction pattern of these compounds against various tubulin isoforms is important for selective targeting of cancer cells. Structural modification can potentially enhance the selective targeting ability of these molecules.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ya-Xin Sun, Jian Song, Li-Jun Kong, Bei-Bei Sha, Xin-Yi Tian, Xiu-Juan Liu, Tao Hu, Ping Chen, Sai-Yang Zhang
Summary: This study designed a series of novel bis-substituted aromatic amide dithiocarbamate derivatives as tubulin inhibitors with potential anticancer activities. Among them, compound 20q exhibited the most potent antiproliferative activity and was identified as a tubulin inhibitor targeting the colchicine binding site.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Mohammed Hawash, Deniz Cansen Kahraman, Abdurrahman Olgac, Sezen Guntekin Ergun, Ernest Hamel, Rengul Cetin-Atalay, Sultan Nacak Baytas
Summary: In this study, novel compounds with polar and nonpolar substitutions on the prop-2-en-1-on linker of the trans-indol-3-ylacrylamide scaffold were designed and synthesized. The antiproliferative activities of these compounds against hepatocellular carcinoma were evaluated, and five of the compounds showed moderate antitumor activities. Compound 13 was identified as a tubulin polymerization inhibitor and induced G2/M-phase arrest in Huh7 cells. The results suggest that polar substitutions enhance the potency against tubulin polymerization.
JOURNAL OF MOLECULAR STRUCTURE
(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, 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)
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)
Article
Chemistry, Medicinal
Ting Xiao, Jia-Fan Tang, Ge Meng, Christophe Pannecouque, Yuan-Yuan Zhu, Gen-Yan Liu, Zhi-Qiang Xu, Feng-Shou Wu, Shuang-Xi Gu, Fen-Er Chen
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Chao Wang, Xiao-Wen Liu, Ting Xiao, Zhi-Qiang Xu, Shuang Cao, Hai-Feng Wang, Qiong-Jiao Yan, Shuang-Xi Gu, Yuan-Yuan Zhu
MEDICINAL CHEMISTRY RESEARCH
(2020)
Article
Chemistry, Applied
Haifeng Wang, Xiangli Sun, Manman Hu, Xiaoyi Zhang, Lele Xie, Shuangxi Gu
ADVANCED SYNTHESIS & CATALYSIS
(2020)
Article
Chemistry, Medicinal
Yue Wang, Shuang-Xi Gu, Qiuqin He, Renhua Fan
Summary: The development history of HIV-1 IN strand transfer inhibitors (INSTIs) was briefly illustrated in the review. The currently approved INSTIs play a significant role in antiretroviral therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Spectroscopy
Zhiqiang Xu, Yabin Luo, Yu Hong, Ziru Liu, Ming-Xing Zhang, Shuang-Xi Gu, Jun Yin
Summary: A ratiometric fluorescent probe (NED) for detecting phosgene was developed, showing high sensitivity and selectivity, along with a paper test strip for visually detecting gaseous phosgene.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Review
Chemistry, Organic
Wei Ming, Sha Hu, Ye Liu, Qu-Ao-Wei Li, Yuan-Yuan Zhu, Shuang-Xi Gu
Summary: This review summarizes recent developments in the chemical synthesis of β-NMN from various starting materials, providing valuable references for the investigation of new synthetic techniques and the further development and large-scale application of β-NMN.
CURRENT ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Wei Ming, Wen-Long Lu, Christophe Pannecouque, Jiong Chen, Hai-Feng Wang, Ya-Qi Xiao, Sha Hu, Shuang-Xi Gu, Yuan-Yuan Zhu, Fen-Er Chen
Summary: The hybrids of delavirdine and piperdin-4-yl-aminopyrimidine (DPAPYs) were synthesized and evaluated for their anti-HIV activities and inhibitory activities against HIV-1 reverse transcriptase. The results showed that all the compounds demonstrated moderate to excellent potency against wild-type HIV-1 and specific RT inhibitory activity. Compound 4d exhibited the most potent activity against wild-type HIV-1 and showed good to excellent potency against various HIV-1 mutants.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Hanrui Jiang, Huan Xiong, Shuang-Xi Gu, Mingliang Wang
Summary: Proteolysis targeting chimeras (PROTACs) technology enables the development of drugs for non-druggable targets. However, there is a limited number of E3 ubiquitin ligase ligands available, which limits the design of PROTAC molecules. Most clinical trials on PROTAC molecules are based on CRBN ligands, highlighting the importance of structural optimization of E3 ubiquitin ligase ligands.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Organic
Chenzong Li, Xun Xiang, Xianghe Zhang, Zhao-Lin He, Shuang-Xi Gu, Xiu-Qin Dong
Summary: Chiral benzoxazinones and 4H-3,1-benzoxazines are important motifs found in pharmaceuticals and biological molecules. This study successfully developed a kinetic resolution process for racemic benzoxazinones through iridium-catalyzed asymmetric intramolecular allylation, providing a wide range of chiral benzoxazinones and 4H-3,1-benzoxazines with excellent results. The protocol demonstrated broad substrate scope and good functional group tolerance, and the chiral 4H-3,1-benzoxazine products could be easily transformed into other useful optically active heterocycles.
Review
Chemistry, Multidisciplinary
Zhihua Gong, Sha Hu, Xueping Jin, Lei Yu, Yuanyuan Zhu, Shuangxi Gu
Summary: Compared to the original drugs, phosphoester prodrugs have several advantages including improved targeting, stability, and bioavailability of the drugs, reduced toxicity and side effects, masked unpleasant odor, enhanced water solubility, and better access to the drugs. The phosphorylation of hydroxyl-containing drugs is an essential method for prodrug design. Different phosphorylation reagents, such as tetracoordinated P(V) compounds, tricoordinated P(III) compounds, and H-phosphite esters, have been reviewed for their synthesis and application in phosphoester prodrugs. The article concludes with a summary of the advantages and limitations of these phosphorylation reagents and prospects for future development based on continuous flow reaction technology.
PROGRESS IN CHEMISTRY
(2022)
Review
Chemistry, Organic
Ge Rui, Zhu Yuanyuan, Wang Haifeng, Gu Shuangxi
Summary: This article reviews the methods used to determine the absolute configuration of chiral compounds and provides an overview of their principles and applications.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Organic
Ding Liu, Yuanyuan Zhu, Shuangxi Gu, Fener Chen
Summary: The halogenation of organic compounds is a crucial transformation in organic synthesis, but traditional batch reactions face issues like high exothermicity. Flow chemistry offers unique advantages such as high mixing efficiency and enhanced process safety. Systematic summaries of flow chemistry progress in fluorination, chlorination, bromination and iodization have been made, with prospects for future development.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mengqian Yang, Jingran Deng, Huifang Su, Shuangxi Gu, Jie Zhang, Aiguo Zhong, Fengshou Wu
Summary: A new organic small molecule T-BDP was designed and synthesized with strong aggregation-induced emission in water, showing potential in fluorescence imaging-guided PDT/PTT synergistic tumor therapy. T-BDP NPs exhibited significant aggregation-induced emission performance and subcellular localization in cancer cells, indicating promising applications in cancer treatment under fluorescence imaging guidance.
MATERIALS CHEMISTRY FRONTIERS
(2021)
Review
Pharmacology & Pharmacy
Shuang-Xi Gu, Yuan-Yuan Zhu, Chao Wang, Hai-Feng Wang, Gen-Yan Liu, Shuang Cao, Lu Huang
CURRENT OPINION IN PHARMACOLOGY
(2020)