Article
Biochemistry & Molecular Biology
Iredia D. D. Iyamu, Yingzhao Zhao, Prakash T. T. Parvatkar, Bracken F. F. Roberts, Debora R. R. Casandra, Lukasz Wojtas, Dennis E. E. Kyle, Debopam Chakrabarti, Roman Manetsch
Summary: A compound with promising antimalarial activity against chloroquine-resistant and chloroquine-sensitive strains of the parasite was identified through screening and structure-activity relationship studies. The essential features necessary for its activity and properties were determined through extensive research.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
S. Maheen Abdul Rahman, Jasvinder Singh Bhatti, Suresh Thareja, Vikramdeep Monga
Summary: Malaria is a deadly parasitic disease claiming millions of lives annually, and the development of drug-resistant strains has reduced the effectiveness of frontline medicines. The design and development of hybrid molecules containing pharmacophoric features of different lead molecules represents a unique strategy for next-generation antimalarial drugs. Triazole derivatives have shown potential antimalarial activities and have become essential units in medicinal chemistry.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Shrawan Kumar Mangawa, Shailja Singh
Summary: Despite scientific progress, malaria remains a global burden that causes thousands of deaths annually. The only option for reducing malaria mortality and morbidity is chemotherapy, but due to drug resistance and toxicity, scientists must explore beyond conventional medicinal chemistry. Metal-based hybrids, including ferrocene compounds, have shown potential as antimalarial agents, with Ferroquine being the most advanced organometallic compound developed and showing great potency in clinical trials against both drug-sensitive and drug-resistant malaria.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Deblina Roy, Mohammad Anas, Ashan Manhas, Satyen Saha, Niti Kumar, Gautam Panda
Summary: In this study, a series of quinoline-imidazole hybrid compounds were synthesized and evaluated for their blood-stage antimalarial activity against Plasmodium falciparum. The results showed that one of the compounds exhibited significant antimalarial efficacy with low cytotoxicity and high selectivity. Furthermore, the study revealed the influence of substituents on the quinoline ring and the role of stereochemistry in the inhibitory activity.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mohit K. Tiwari, Paolo Coghi, Prakhar Agrawal, Dharmendra K. Yadav, Li Jun Yang, Qiu Congling, Dinkar Sahal, Vincent Kam Wai Wong, Sandeep Chaudhary
Summary: A series of lipophilic, halogenated-arylvinyl-1,2,4-trioxanes were synthesized and evaluated for their in vitro anti-plasmodial activity, with ten analogues showing potent activity and selective potential against Plasmodium cells. The most active compound, arylvinyl-1,2,4-trioxane 8f(2), exhibited significant cytotoxic potential in comparison to standard drugs against lung cancer cell lines. Furthermore, in-silico docking studies demonstrated strong virtual interaction of the potent halogenated 1,2,4-trioxanes with the epidermal growth factor receptor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Nicolas Chopin, Julien Bosson, Shinya Iikawa, Stephane Picot, Anne-Lise Bienvenu, Adeline Lavoignat, Guillaume Bonnot, Mickael Riou, Corinne Beauge, Vanaique Guillory, Christophe Biot, Guillaume Pilet, Matthieu Chesse, Elisabeth Davioud-Charvet, Mourad Elhabiri, Jean-Philippe Bouillon, Maurice Medebielle
Summary: A series of ferrocenyl-containing gamma-hydroxy-gamma-lactam tetramates were prepared through a ring opening-ring closure process in the presence of ferrocenyl alkylamines. These compounds exhibited good antiplasmodial activity and selective antiparasitic activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Hao Zhang, John Ginn, Wenhu Zhan, Annie Leung, Yi J. Liu, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Mayako Michino, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Nigel Liverton, Michael Foley, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Targeting the Plasmodium proteasome is a promising strategy to combat malaria, especially with the increasing reports of resistance to current therapies. In this study, we conducted structure-activity relationship studies on a macrocyclic scaffold and identified compound TDI-8414, which showed potent antiparasitic activity, high selectivity, improved solubility, and enhanced metabolic stability.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Food Science & Technology
Zhiyun Peng, Guangcheng Wang, Qiao-Hui Zeng, Yufeng Li, Haiquan Liu, Jing Jing Wang, Yong Zhao
Summary: Tyrosinase is a copper-containing oxidation enzyme responsible for melanin production and plays a key role in browning, antibiotic resistance, pigment formation, etc. Synthetic tyrosinase inhibitors have great potential applications and have been widely reported in recent years.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Chemistry, Multidisciplinary
Karolina Kowalczyk, Andrzej Blauz, Daniel Moscoh Ayine-Tora, Christian G. Hartinger, Blazej Rychlik, Damian Plazuk
Summary: Derivatives of ispinesib and its (S) analogue, containing ferrocenyl moieties or bulky organic substituents, were prepared to combine multiple biologically-active components in a single molecule. Several of these compounds demonstrated higher antiproliferative activity than ispinesib, with nanomolar IC50 values against cell lines. The improved activity may be attributed to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Scott Eagon, Jared T. Hammill, Kasey Fitzsimmons, Natalie Sienko, Brandon Nguyen, Jarvis Law, Aashrita Manjunath, Steven P. Wilkinson, Kara Thompson, Julia Elizabeth Glidden, Amy L. Rice, Mofolusho O. Falade, Joshua J. Kimball, Celine DiBernardo, R. Kiplin Guy
Summary: In the search for new anti-malarial drugs, this study reports the discovery of a derivative with potential efficacy against Plasmodium falciparum but without detectable toxicity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Geraldo Jose da Silva Neto, Leandro Rocha Silva, Rafael Jorge Melo de Omena, Anna Caroline Campos Aguiar, Yasmin Annunciato, Barbara Santos Rossetto, Marcos Leoni Gazarini, Luana Heimfarth, Lucindo Jose Quintans-Junior, Edeildo Ferreira da Silva-Junior, Mario Roberto Meneghetti
Summary: Although current drugs are available for malaria treatment, the development of resistant strains of the parasite calls for the need of new drugs. This study synthesized four dual pharmaceutical compounds with potential antimalarial and anti-inflammatory activities, with DEQ showing the highest activity and IBUCEQ and TOQ being the most promising candidates.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Applied
Marcel Cardoso de Noronha, Rodrigo Rezende Cardoso, Carolina Thomaz dos Santos D'Almeida, Mariana Araujo Vieira do Carmo, Luciana Azevedo, Vinicius Goncalves Maltarollo, Jose Ivo Ribeiro Junior, Monique Renon Eller, Luiz Claudio Cameron, Mariana Simoes Larraz Ferreira, Frederico Augusto Ribeiro de Barros
Summary: This study demonstrates the changes in physicochemical and microbiological composition of black tea kombucha during fermentation, as well as the alteration in its phenolic profile. Additionally, the study evaluates the antimalarial potential of black tea kombucha.
Article
Biochemistry & Molecular Biology
Jiri Kos, Gilles Degotte, Dominika Pindjakova, Tomas Strharsky, Timotej Jankech, Tomas Gonec, Pierre Francotte, Michel Frederich, Josef Jampilek
Summary: A series of thirty-seven ring-substituted N-arylcinnamanilides prepared by microwave-assisted synthesis were shown to exhibit strong antimalarial activity in primary screening. Some of these compounds demonstrated activity comparable to the standard drug chloroquine and showed no cytotoxic effects, making them promising candidates for further investigation.
Review
Environmental Sciences
Mingzhu Ren, Sihan Sun, Yiqiu Wu, Yanchun Shi, Zhou-jun Wang, Hongbin Cao, Yongbing Xie
Summary: This paper introduces the widespread application of advanced oxidation processes (AOPs) in treating highly toxic and harmful substances in wastewater. It discusses the influence of different reactive oxygen species (ROS) on the degradation rate based on the structural differences of aromatic compounds. The paper also analyzes the structure-activity relationship of pollutants and highlights the impact of various experimental factors.
Article
Biochemistry & Molecular Biology
Fernanda Valerio Lopes, Pedro Henrique Fazza Stroppa, Juliane Aparecida Marinho, Roberta Reis Soares, Lara de Azevedo Alves, Priscila Vanessa Zabala Capriles Goliatt, Clarice Abramo, Adilson David da Silva
Summary: This study evaluated the antimalarial activity of triazole derivatives, with compound 5 showing promising potential for further development in antimalarial chemotherapy. In vitro and in vivo studies showed that compound 5 had significant parasitemia suppression and minimal cytotoxicity, making it a leading candidate for future research in antimalarial drug development.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
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)