Article
Multidisciplinary Sciences
Rizk E. Khidre, Ibrahim Ali M. Radini
Summary: A series of novel compounds were synthesized and evaluated for their potential as DNA gyrase inhibitors and antimicrobial agents. Among them, compound 13a exhibited good antibacterial and antifungal activities.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Xiang Nan, Qiu-Xu Wang, Shao-Jun Xing, Zhi-Gang Liang
Summary: In this study, four series of thiazole/thiadiazole carboxamide-derived analogues were designed, synthesized, and evaluated as novel c-Met inhibitors for antitumor therapy. Compound 51am was identified as the most promising inhibitor with significant activity against c-Met and several c-Met mutants. Mechanistically, 51am not only induced cell cycle arrest and apoptosis in MKN-45 cells but also inhibited c-Met phosphorylation in both cell and cell-free systems. In addition, 51am showed good pharmacokinetic properties in mice and its binding mode with c-Met and VEGFR-2 provided new insights for the discovery of selective c-Met inhibitors. These findings suggest that 51am has the potential to be further developed as an antitumor candidate.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Surendar Chitti, Kevin Van Calster, Davie Cappoen, Adinarayana Nandikolla, Yogesh Mahadu Khetmalis, Paul Cos, Banoth Karan Kumar, Sankaranarayanan Murugesan, Kondapalli Venkata Gowri Chandra Sekhar
Summary: In the search for new anti-mycobacterial agents, the importance of imidazo-[2,1-b]-thiazole and benzo-[d]-imidazo-[2,1-b]-thiazole carboxamide derivatives was revealed. Several series of novel derivatives were designed, predicted, and synthesized. The most active derivatives showed selective inhibition against Mycobacterium tuberculosis and no activity against non-tuberculous mycobacteria. Molecular docking and dynamics studies were also conducted to understand the binding pattern and stability of the protein-ligand complex.
Article
Chemistry, Organic
Reem A. K. Al-Harbi, Heba A. Emam, Samir Y. Abbas
Summary: This study aimed to synthesize new 2-pyridinone and thiazole derivatives bearing coumarin moiety. Several attempts were made using different reaction conditions, but the desired products were not obtained as expected.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lifei Du, Xiaoyu Wang, Guonan Cui, Bailing Xu
Summary: A series of thiazole derivatives with alicyclic heterocycles were designed, synthesized, and tested as potential Pin1 inhibitors. Compound 9p was identified as the most potent Pin1 inhibitor in the series, and introducing an alicyclic ring with an H-bond acceptor was found to improve binding affinity according to structure-activity relationship and molecular modeling studies.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zesheng Hao, Bin Yu, Wei Gao, Haoyin Chen, Dongyan Yang, You Lv, Yue Zhang, Lei Chen, Zhijin Fan
Summary: Twenty-one novel pyrazole-thiazole carboxamide derivatives were synthesized and evaluated for their fungicidal activities, with compounds 6d and 6j showing promising results both in vitro and in vivo, particularly compound 6j demonstrating good protective activity against Rhizoctonia solani and Puccinia sorghi Schw.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Xinyu Wang, Zehui Tan, Fuyi Wang, Jiahao Zhang, Juanjuan Yang, Shuyu Liu, Nan Jiang, Xin Zhai
Summary: A novel TrkA inhibitor, compound 19c, was developed using a scaffold hopping strategy. It showed excellent anti-proliferative activity on TrkA-positive KM-12 cells and demonstrated higher selectivity for TrkA over TrkB and TrkC.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Fei Meng, Zixin Yan, Yuexiao Lu, Xiaobin Wang
Summary: A series of flavonoid derivatives containing thiazole scaffold were synthesized and evaluated for their antifungal effects. The results showed that some target compounds exhibited significant antibacterial activity against various plant fungi, surpassing that of the natural flavonoid quercetin.
Article
Chemistry, Medicinal
Thais Batista Fernandes, Natanael Dante Segretti, Felipe Rebello Lourenco, Thalita Marcilio Candido, Andre Rolim Baby, Euzebio Guimaraes Barbosa, Roberto Parise-Filho
Summary: The study designed and synthesized arylsulfonylhydrazones as potential FabH inhibitors, evaluated their antimicrobial, antioxidant activities, and cytotoxicity, with the most active compound showing activity against S. aureus and E. coli, and being non-toxic to human lung fibroblast cells. Molecular docking studies suggested that the sulfonylhydrazone moiety plays an important role in interacting with FabH, while the methylcatechol ring is involved in pi-pi stacking interaction. Overall, arylsufonylhydrazones show promise as scaffolds for the design of new antimicrobial agents.
MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhen Zhang, Peichang Cao, Mengyuan Fang, Tingfeng Zou, Jihong Han, Yajun Duan, Huajian Xu, Xiaoxiao Yang, Qing-Shan Li
Summary: In this study, a novel compound E26 was designed and synthesized to treat sepsis by inhibiting inflammatory response. Experimental results demonstrated that compound E26 exhibited potent anti-inflammatory activity by suppressing the production of various inflammatory factors through blocking the MAPKs signaling pathway, and showed significant efficacy in a mouse model of sepsis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
Meng Li, Weiwei Wang, Xiang Cheng, Yunxiao Wang, Yao Chen, Jiexiu Gong, Xihao Chang, Xianhai Lv
Summary: In this study, a series of pyrazole carboxamide thiazole derivatives were designed, synthesized, and evaluated for their antifungal activities against plant pathogens. The bioassay results showed that several compounds exhibited good antifungal activities, with compounds 6i and 19i showing better efficacy than the control drug. Compound 23i also displayed significant inhibitory activity against a potato pathogen. Scanning electron microscopy analyses revealed that compound 6i could disrupt the surface morphology of the target fungus.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
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
Xin Dang, Shuwen Lei, Shuhua Luo, Yixin Hu, Juntao Wang, Dongdong Zhang, Dan Lu, Faqin Jiang, Lei Fu
Summary: The study assessed the anti-cancer activities of a novel family of TPP-thiazole derivatives, finding that these compounds exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.
BIOORGANIC CHEMISTRY
(2021)
Article
Agriculture, Multidisciplinary
Jian-Long Li, Jing-Fang Yang, Li-Ming Zhou, Meng Cai, Zhong-Qiao Huang, Xi-Li Liu, Xiao-Lei Zhu, Guang-Fu Yang
Summary: Oomycetes, particularly Phytophthora species, pose significant threats to global food security and natural ecosystems. This study used AlphaFold 2 to generate the OSBP model of Phytophthora capsici and investigated the binding mechanism of the fungicide OXA. Based on this, a series of OXA analogues were designed, and compound 2l showed comparable control efficiency to OXA. The findings suggest that 2l could serve as a lead compound for the development of new OSBP fungicides.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Alexander T. Bakker, Ioli Kotsogianni, Liza Mirenda, Verena M. Straub, Mariana Avalos, Richard J. B. H. N. van den Berg, Bogdan I. Florea, Gilles P. van Wezel, Antonius P. A. Janssen, Nathaniel I. Martin, Mario van der Stelt
Summary: Phenotypic screening identifies a series of 1,3,4-oxadiazole-3-ones as novel antibacterial compounds with a polypharmacological mode of action against multidrug-resistant Staphylococcus aureus. Activity-based protein profiling reveals several cysteine and serine hydrolases as relevant targets. This study highlights oxadiazolones as a promising antibacterial chemotype with central roles of FabH, FphC, and AdhE.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
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)