Article
Biochemistry & Molecular Biology
Eslam M. H. Ali, Mohammed S. Abdel-Maksoud, Usama M. Ammar, Karim Mersal, Kyung Ho Yoo, Park Jooryeong, Chang-Hyun Oh
Summary: The study developed and synthesized a series of compounds with anticancer potential, demonstrating promising activity in various cancer types. Two compounds showed notable anti-cancer effects on Melanoma cancer cell lines.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Mohamed A. Abdelgawad, Arafa Musa, Atiah H. Almalki, Sami Alzarea, Ehab M. Mostafa, Mostafa M. Hegazy, Gomaa Mostafa-Hedeab, Mohammed M. Ghoneim, Della Gt Parambi, Rania B. Bakr, Nayef S. Al-Muaikel, Abdullah S. Alanazi, Metab Alharbi, Waqas Ahmad, Syed Na Bukhari, Mohammad M. Al-Sanea
Summary: In this study, three potential dual EGFR and COX-2 inhibitors were prepared and evaluated, with compounds C4 and G4 showing good inhibitory activity and cytotoxicity against multiple cancer cell lines. Virtual docking study results were consistent with experimental findings, confirming the inhibitory activities of the synthesized compounds for both COX and EGFR.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Chemistry, Organic
Hongchen Li, Lidong Shan, Chulong Liu, Nan Liu, Xinyan Wang, Yuefei Hu
Summary: A novel method for chemospecific C3- and C2-olefinations of isatins using TfOH-promotion has been developed, presenting the first examples of Grob fragmentation with isatins and amides as substrates.
Article
Biochemistry & Molecular Biology
Wagdy M. Eldehna, Sara T. Al-Rashood, Tarfah Al-Warhi, Razan O. Eskandrani, Amal Alharbi, Ahmed M. El Kerdawy
Summary: In this study, three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3 beta inhibitors targeting breast cancer. The N-1 -unsubstituted oxindole derivatives showed potent cytotoxic activity, while the N-1-substituted derivatives exhibited moderate to weak activity on breast cancer cell lines. The most potent compounds caused cell cycle arrest in the G2/M phase by inhibiting CDK2/GSK-3 beta, as demonstrated by enzyme inhibition assays and molecular docking studies.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Organic
Deeksha, Bittu, Ritesh Singh
Summary: C3-fluorinated oxindoles are important scaffolds with diverse biological activities. They hold tremendous potential in drug research and can be used as starting materials for synthesizing other fluorine-containing structures. Various approaches have been developed to synthesize C3-fluorinated oxindoles, and this review focuses on the strategies for obtaining C3-difluoro and monofluorooxindoles using intermolecular and intramolecular methods. The key findings and mechanisms of these strategies are discussed.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Yuichi Sawaguchi, Ryuta Yamazaki, Yukiko Nishiyama, Masayuki Mae, Atsuhiro Abe, Hiroyuki Nishiyama, Fukiko Nishisaka, Tatsuya Ibuki, Toshio Sasai, Takeshi Matsuzaki
Summary: The study investigated novel pan-Pim kinase inhibitors with imidazopyridazine and thiazolidinedione structure, which showed high inhibitory activities against Pim kinases in various cancer cell lines. The compounds suppressed Pim kinase substrate phosphorylation, induced cell cycle arrest at the G1 phase, and triggered apoptosis in cultured cancer cells. In tumor xenograft models, the compounds exhibited antitumor activities, suggesting potential as effective inhibitors for various types of cancer cells.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ying-Yue Yang, Wan-Li Wang, Xia-Tong Hu, Xin Chen, Yang Ni, Yan-Hua Lei, Qi-Yuan Qiu, Long-Yue Tao, Tian -Wen Luo, Ning-Yu Wang
Summary: The mammalian target of rapamycin (mTOR) has been proven to be an effective target for cancer therapy. Rapalogs and mTOR kinase inhibitors (TORKi) have been developed and clinically validated in several types of malignancies, with TORKi showing better antitumor activity by inhibiting both mTORC1 and mTORC2. However, the clinical development of current TORKi candidates has been relatively slow, and there is a need to develop more TORKi with novel scaffold to expand the current pipelines.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Heba A. Elsebaie, Eman A. El-Bastawissy, Kamel M. Elberembally, Eman F. Khaleel, Rehab Mustafa Badi, Moataz A. Shaldam, Wagdy M. Eldehna, Haytham O. Tawfik, Tarek F. El-Moselhy
Summary: The current study discovered 15 new thieno[2,3-d]pyrimidine derivatives with potential anticancer action and further validated the inhibitory ability of some compounds on specific cell lines, as well as their role in cell cycle and apoptosis. The biological activities of the most potent compound were also explained through computational methods.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Bruno Oyallon, Marie Brachet-Botineau, Cedric Loge, Thomas Robert, Stephane Bach, Sajida Ibrahim, William Raoul, Cecile Croix, Pascal Berthelot, Jean Guillon, Noel Pinaud, Fabrice Gouilleux, Marie-Claude Viaud-Massuard, Caroline Denevault-Sabourin
Summary: New quinoxaline derivatives acting as dual Pim1/2 inhibitors showed potent inhibition of Pim-1 and Pim-2 enzymes in vitro, and were able to inhibit the growth of multiple myeloma and colorectal carcinoma cell lines expressing high levels of Pim-1/2 kinases.
Article
Biochemistry & Molecular Biology
Darshan Joshi, Rajesh Bahekar, Shubhangi Soman, Pradip Jadav, Dipam Patel, Amitgiri Goswami, Jignesh Pethani, Jeevan Kumar, Jitendra Patel, Rajesh Sundar, Poonamgiri Goswami, Krishnarup Goshdastidar, Hoshang Patel, Ankit Patel, Debdutta Bandyopadhyay, Abhijit Chattarjee, Manoranjan Sharma, Mukul Jain, Ranjit Desai
Summary: In this study, novel structural optimizations were conducted to discover effective Bruton's Tyrosine Kinase (BTK) inhibitors for the treatment of autoimmune disorders. Compound 14b was identified as a potent and selective BTK inhibitor with improved oral bioavailability. It displayed strong efficacy in in vitro and in vivo assays, making it a viable therapeutic option for autoimmune disorders.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sarah H. M. Khairat, Mohamed A. Omar, Fatma A. F. Ragab, Sonam Roy, Ahmad A. Turab Naqvi, Ahmed S. Abdelsamie, Anna K. H. Hirsch, Shadia A. Galal, Md Imtaiyaz Hassan, Hoda El Diwani
Summary: A novel series of benzimidazoles was synthesized and evaluated as SphK1 inhibitors, with most compounds showing effective inhibition against SphK1 and compound 41 standing out as the most potent one. Molecular docking revealed the potential of these compounds to fit well into the ATP-binding site of SphK1 and form hydrogen bond interactions with catalytically important residues, suggesting their therapeutic potential in the clinical management of SphK1-associated diseases.
ARCHIV DER PHARMAZIE
(2021)
Article
Chemistry, Medicinal
Shi Ding, Ziye Gao, Ziqiang Hu, Rui Qi, Xiangshan Zheng, Xiaoyong Dong, Mingjuan Zhang, Jiwei Shen, Tian Long, Yan Zhu, Lu Tian, Wenshan Song, Ruoqing Liu, Ying Li, Jiahuan Sun, Wenwen Duan, Ju Liu, Ye Chen
Summary: A series of osimertinib derivatives were synthesized and evaluated for their inhibitory activities against mutant EGFR kinases. Compound 9h showed significant inhibitory activity against various EGFR kinases, while compound 22a exhibited excellent selectivity against the L858R/T790M/C797S mutant EGFR kinase.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Tianxiao Wu, Chu Zhang, Ruicheng Lv, Qiaohua Qin, Nian Liu, Wenbo Yin, Ruifeng Wang, Yin Sun, Xiaoyan Wang, Yixiang Sun, Dongmei Zhao, Maosheng Cheng
Summary: A potent and selective TRK inhibitor 19m was developed through rational drug design strategy, which effectively inhibits the proliferation of TRK-dependent cell lines and shows good kinase selectivity and drug safety. The compound exhibits favorable pharmacokinetic properties and a pharmacophore model guided by experimental results is proposed to help researchers find TRK inhibitors more efficiently.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Bin Zhang, Zhikun Liu, Shengjin Xia, Qingqing Liu, Shaohua Gou
Summary: Multi-target, especially dual-target, drug design is a popular research field in cancer treatment. This study developed quinazoline derivatives as dual EGFR/CAIX inhibitors, with compound 8v showing potent anticancer activity against mutant-type lung cancer cells, especially under hypoxic conditions. Mechanism studies revealed that 8v exhibited strong inhibitory effects on both EGFR(T790M) and CAIX enzymes, making it a promising candidate for further research in cancer therapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Liang Xia, Lin Jiang, Tingting Du, Songwen Lin, Tianning Xiong, Shouguo Peng, Hua Tian, Kehui Zhang, Deyu Wu, Li Sheng, Ming Ji, Xiaoguang Chen, Heng Xu
Summary: Phosphatidylinositol 3-kinase (PI3K) signaling is a common alteration in cancer and a key target for cancer drug development. In this study, a novel series of bivalent PI3K inhibitors with improved potency and anti-proliferative activity were designed and synthesized. The lead compound showed significant inhibition of the PI3K signal pathway, induction of G1 cell cycle arrest, and inhibition of colony formation and cell migration. It also demonstrated dose-dependent anticancer efficacy in a mouse model.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Hong-Bao Sun, Liang Gong, Yu-Biao Tian, Jin-Gui Wu, Xia Zhang, Jie Liu, Zhengyan Fu, Dawen Niu
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2018)
Article
Chemistry, Medicinal
Zhu-Jun Yu, Sha Liu, Shu Zhou, Hui Li, Fan Yang, Ling-Ling Yang, Yong Wu, Li Guo, Guo-Bo Li
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Chemistry, Medicinal
Sha Liu, Li Jing, Zhu-Jun Yu, Chengyong Wu, Yongxiang Zheng, En Zhang, Qiang Chen, Yamei Yu, Li Guo, Yong Wu, Guo-Bo Li
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Organic
Chen Zhang, Yan-chi Pu, Zhu-Jun Yu, Cheng-yong Wu, Jurgen Brem, Michael A. McDonough, Christopher J. Schofield, Guo-Bo Li, Yong Wu
ORGANIC CHEMISTRY FRONTIERS
(2018)
Article
Chemistry, Multidisciplinary
Liang Gong, Hong-Bao Sun, Li-Fan Deng, Xia Zhang, Jie Liu, Shengyong Yang, Dawen Niu
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Chemistry, Organic
Yao Hu, Ting Wang, Yanzhao Liu, Ruifang Nie, Ninghong Yang, Qiantao Wang, Guo-Bo Li, Yong Wu
Article
Biochemistry & Molecular Biology
Jiayu Sun, Jie Li, Hongbao Sun, Chunling Li, Haoxing Wu
Summary: The study presents the concise synthesis of a series of aryl-functionalized cyclobutene analogues using commercially available starting materials, demonstrating their suitability as stable substrates for bioorthogonal tetrazine ligation.
Article
Pharmacology & Pharmacy
Qingqing Dai, Yuhang Yan, Xiangli Ning, Gen Li, Junlin Yu, Ji Deng, Lingling Yang, Guo-Bo Li
Summary: AncPhore is a versatile tool for drug discovery that improves prediction ability on different types of target proteins by analyzing pharmacophore features and using anchor pharmacophores. It has the potential to efficiently identify new inhibitors for various protein targets.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Medicinal
Shuo Yuan, Bo Wang, Qing-Qing Dai, Xiao-Nan Zhang, Jing-Ya Zhang, Jia-Hui Zuo, Hui Liu, Zhe-Sheng Chen, Guo-Bo Li, Shaomeng Wang, Hong-Min Liu, Bin Yu
Summary: YS-370 is a highly effective P-gp inhibitor capable of reversing multidrug resistance and achieving good results when administered orally. The inhibitor does not alter the expression or subcellular localization of P-gp, but increases the intracellular accumulation of drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zihao Shen, Yu-Hang Yan, Shuo Yang, Sang Zhu, Yuan Yuan, Zhiqiang Qiu, Huan Jia, Ruiqiong Wang, Guo-Bo Li, Honglin Li
Summary: Protein kinases play a central role in signal transduction and are important drug targets for therapeutic intervention. The ProfKin web server, based on the KinLigDB database, provides a versatile tool for structure-based kinase profiling, offering a wealth of information to guide drug discovery and development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Gen Li, Qing-Qing Dai, Guo-Bo Li
Summary: Metalloenzymes are enzymes that rely on metal ions, and comparing their active sites is crucial for enzyme design, function research, and inhibitor development. MeCOM is a method for comparing metalloenzyme active sites, which can accurately identify and compare active sites, evaluate similarity, and establish new associations between metalloenzymes.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
You-Cai Xiao, Jun-Lin Yu, Qing-Qing Dai, Gen Li, Guo-Bo Li
Summary: Metalloenzymes play critical roles in biological processes and are important therapeutic targets. This perspective focuses on the importance of exploiting metal-binding pharmacophores, specifically boron-containing MBPs, in inhibitor development targeting metalloenzymes. The challenges and design concepts regarding boron-containing MBPs are discussed, with emphasis on the unique binding modes with metalloenzyme active sites.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Organic
Hongbao Sun, Qinghe Xue, Chang Zhang, Haoxing Wu, Ping Feng
Summary: Bioorthogonal chemistry, particularly tetrazine-based reactions, has gained significant attention for its applications in biological systems, such as cellular labeling, live-cell imaging, diagnosis, drug release, and oncotherapy. However, limited commercial starting materials for de novo tetrazine synthesis have led to the exploration of derivatization approaches to enhance the applications of tetrazine bioorthogonal reactions. This review summarizes recent advances in tetrazine scaffold-based derivatizations and highlights both the advantages and limitations of these methods in bioorthogonal chemistry.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Yuesen Shi, Huimin Xing, Tianle Huang, Xuexin Liu, Jian Chen, Xiaoyu Guo, Guo-Bo Li, Yong Wu
CHEMICAL COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Sha Liu, Sen Ji, Zhu-Jun Yu, Hua-Li Wang, Xu Cheng, Wei-Jian Li, Li Jing, Yamei Yu, Qiang Chen, Ling-Ling Yang, Guo-Bo Li, Yong Wu
CHEMICAL BIOLOGY & DRUG DESIGN
(2018)