Review
Chemistry, Medicinal
Bi Liu, Dan Jiang, Guowen Hu
Summary: Bacterial infections remain a major cause of patient morbidity and mortality worldwide, and their treatment is challenging due to rapidly evolving resistance mechanisms. Hybridization is a promising strategy for developing novel antibacterial drugs, and combining the pharmacophores of isatin with other antibacterial agents may create candidates with broad-spectrum activity against drug-resistant pathogens.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Mingxia Song, Yi Hua, Yuxin Liu, Xunli Xiao, Haihong Yu, Xianqing Deng
Summary: The overuse and misuse of antimicrobial drugs have led to a critical global health problem of antibacterial resistance. This study designed, synthesized, and elucidated a novel set of ciprofloxacin-indole/acetophenone hybrids through structural analysis. These hybrids demonstrated excellent inhibitory activity against gram-positive and gram-negative pathogens, including multidrug-resistant clinical isolates. Compound 8b showed higher antibacterial activity and bactericidal capability than ciprofloxacin, making it a promising candidate for further investigations.
Article
Chemistry, Multidisciplinary
Yanhua Wang, Ruiqi Ding, Zijian Tai, Haodong Hou, Feng Gao, Xiangyang Sun
Summary: This study designed and synthesized a series of artemisinin-isatin hybrids and evaluated their antiproliferative activity against breast cancer cells. The preliminary results showed that some of the hybrids exhibited activity against both drug-sensitive and doxorubicin-resistant breast cancer cell lines. Structure-activity relationship analysis revealed the significant influence of linker and substituents on the activity. Certain hybrids displayed the most active anti-cancer activity, comparable to doxorubicin. Therefore, these hybrids could serve as important templates for developing novel anti-breast cancer agents.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Physical
Ping Yang, Jia-Bao Luo, Zi-Zhou Wang, Li-Lei Zhang, Xiao-Bao Xie, Qing-Shan Shi, Xin-Guo Zhang
Summary: Twelve novel fluoroquinolone derivatives were designed and synthesized by introducing N-acylarylhydrazone to the C-7 position of ciprofloxacin. Compound 3k exhibited more potent antibacterial activity against S. aureus compared to ciprofloxacin, while compound 3g showed activity against methicillin-resistant S. aureus (MRSA). Compound 3g exerted bactericidal effects on S. aureus and E. coli, and displayed a higher affinity to DNA topoisomerase IV than ciprofloxacin. Molecular dynamics simulation results confirmed the stable interaction between receptor 3rae and compound 3g. Furthermore, cytotoxicity and hemolysis assays indicated the minimal risk of toxic effects for compounds 3g and 3k.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Francesca Bonvicini, Alessandra Locatelli, Rita Morigi, Alberto Leoni, Giovanna Angela Gentilomi
Summary: Isatin and its derivatives are important heterocycles with various biological activities and are essential building blocks in organic synthesis. In this study, a small library of 18 isatin hybrids were synthesized and evaluated for antimicrobial potential, with two lead compounds showing inhibitory activity against S. aureus at very low concentrations.
Article
Cell Biology
Kinga Lewtak, Paulina Czaplewska, Jerzy Wydrych, Radoslaw Keller, Aldona Nowicka, Krzysztof Skrzypiec, Marta Julia Fiolka
Summary: This study investigated the effect of protein extract from Sida hermaphrodita seeds on Mycobacterium smegmatis and characterized the protein extract using different microscopy and spectroscopy techniques. Results showed that the extract significantly reduced the viability of M. smegmatis cells and induced changes in the cell wall structure. Proteomic analysis revealed the presence of structural, storage, and enzymatic proteins and peptides in the extract, as well as antimicrobial proteins and peptides.
Review
Chemistry, Physical
Aeyaz Ahmad Bhat, Nitin Tandon, Iqubal Singh, Runjhun Tandon
Summary: Bacterial infections are a global health issue with increasing death cases. Antibiotic resistance has rendered available antibiotics ineffective in treating bacterial infections, leading to more problems. In 2019, 1.2 million deaths were reported due to infections caused by antibiotic-resistant bacteria. Pyrrolidine compounds, both synthetic and natural, exhibit significant antibacterial activity and have the least side effects. These compounds have the ability to modulate a wide range of targets, making them promising antibacterial drugs.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Chemistry, Physical
Kajalben B. Patel, Premlata Kumari
Summary: This review summarizes quinoline-based hybrids with antibacterial activity and their structure-activity relationship (SAR), providing insights into the improvement of quinoline-based antibiotics, especially against multidrug-resistant bacterial strains.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Shaohuan Liu, Shu Wang, Dan Xu, Bowen Pan, Linzhi Chen, Shijia Zhao, Zhi Xu, Wei Zhou
Summary: A series of ester tethered dihydroartemisinin-3-(oxime/thiosemicarbazide)isatin hybrids 7a-p were designed, synthesized, and evaluated for their antiproliferative activity against breast cancer cell lines. The hybrids showed potent activity against both drug-sensitive and drug-resistant breast cancers. The structure-activity relationships obtained from this study may aid in the design of more active candidates.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Zhe Zhang, Dong Zhang, Yanhui Zhou, Feifei Wang, An Xin, Feng Gao, Peng Wang, Peng Zhang
Summary: A series of propylene tethered compounds were designed and synthesized, and their antiproliferative activity against lung cancer cell lines was evaluated. Among them, hybrid 6f showed promising activity against drug-resistant lung cancer cells and low cytotoxicity towards normal lung cells. It also exhibited acceptable stability in vitro and in vivo.
ARABIAN JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ruo Wang, Qianru Zhang, Min Chen
Summary: In this study, eleven artemisinin-isatin hybrids tethered via ethylene linker were synthesized and evaluated for their antiproliferative activity against lung cancer cell lines and cytotoxicity towards normal lung epithelial cells. The results showed that these hybrids exhibited potential activity against the cancer cell lines while being non-toxic to normal cells. Moreover, one representative hybrid showed even better potency than traditional chemotherapy drugs and demonstrated excellent safety and selectivity.
ARCHIV DER PHARMAZIE
(2023)
Article
Engineering, Chemical
Zehui Jia, Rui Lv, LiJun Guo, Jiandong Zhang, Rui Li, Jianxin Liu, Caimei Fan
Summary: The use of BiOCl microsphere prepared via hydrolysis method for photocatalytic degradation of CIP has shown promising results in terms of both efficiency and antimicrobial properties of the intermediates. This study sheds light on the potential application of BiOCl in CIP wastewater treatment.
SEPARATION AND PURIFICATION TECHNOLOGY
(2021)
Review
Chemistry, Medicinal
Wenhua Zang, Danxia Li, Li Gao, Shuang Gao, Pengfei Hao, Hua Bian
Summary: Staphylococcus aureus is a significant pathogen that can cause various infections. The emergence of drug-resistant S. aureus, particularly MRSA, has complicated treatment. Ciprofloxacin is an effective broad-spectrum antibacterial agent, but its overuse has led to the emergence of ciprofloxacin-resistant S. aureus. However, ciprofloxacin hybrids have the potential to overcome drug resistance by targeting multiple drug targets in bacteria. This review provides an overview of recent ciprofloxacin hybrids with anti-S. aureus potential, including their structure-activity relationships and mechanisms of action.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Jingyue Gao, Haodong Hou, Feng Gao
Summary: Novel chemotherapeutic agents are urgently needed to combat highly virulent ESKAPE pathogens, and quinolone compounds have shown potential in inhibiting nucleic acid synthesis of these bacteria. However, the rapid development and spread of quinolone resistance in ESKAPE pathogens pose a challenge. Therefore, understanding the structure-activity relationships and mechanisms of action of quinolone hybrids is crucial for the rational design of more effective candidates.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Hamada H. H. Mohammed, Doaa Mohamed Elroby Ali, Mohamed Badr, Ahmed G. K. Habib, Abobakr Mohamed Mahmoud, Sarah M. Farhan, Shimaa Salah Hassan Abd El Gany, Soad A. Mohamad, Alaa M. Hayallah, Samar H. Abbas, Gamal El-Din A. Abuo-Rahma
Summary: A series of N-4 piperazinyl ciprofloxacin derivatives were synthesized and showed broad antibacterial and antifungal activities. Some of the derivatives also exhibited inhibitory activity against DNA gyrase.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)