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)
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
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)
Article
Chemistry, Medicinal
Fernando de Moura Gatti, Renan Augusto Gomes, Amanda Luisa da Fonseca, Elys Juliane Cardoso Lima, Drielli Gomes Vital-Fujii, Alex Guterres Taranto, Fernando de Pilla Varotti, Gustavo Henrique Goulart Trossini
Summary: This study synthesized 35 sulfonylhydrazone derivatives and found one compound, 5b, to be the most promising against resistant strains of Plasmodium falciparum, showing lower cytotoxicity and higher selectivity compared to chloroquine. The structure-activity relationship, statistical analysis, and molecular modeling studies suggested that antiplasmodial activity is related to specific molecular characteristics.
FUTURE MEDICINAL CHEMISTRY
(2021)
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, Multidisciplinary
Morten Suk, Stefanie Lorenz, Klaus Kuemmerer
Summary: Many micropollutants, including pharmaceuticals and other chemicals, are found worldwide in aquatic environments. Transformations during effluent treatment and in the environment can lead to the formation of new chemicals with unknown structure, fate, and toxicity. Designing chemicals that can be fully mineralized or broken down into non-hazardous fragments is considered a green chemistry approach to prevent these issues from the beginning. This study focused on investigating the biodegradability of various N-heterocycles to identify environmentally friendly lead scaffolds, and found that only a small portion of the tested substances were readily biodegradable.
SUSTAINABLE CHEMISTRY AND PHARMACY
(2023)
Article
Plant Sciences
Gervais Mouthe Happi, Liliane Clotilde Dzouemo, Guy Paulin Mouthe Kemayou, Livine Zemo Meikeu, Klev Gaitan Sikam, Mireille Towa Yimtchui, Jacqueline Poffelie Kamegne, Jean Duplex Wansi
Summary: This study aimed to investigate the chemical composition of the endemic plant Urera gravenreuthii Engl. from Cameroon and identify its antiplasmodial compounds. Fifteen distinct compounds were isolated and characterized, with betulinic acid, rutin, quercetin, and lupeol showing good antiplasmodial activity. The study also discussed the structure-activity relationship of these compounds and the chemotaxonomic significance, supporting the plant's classification in the Urticaceae family and its potential as a source for new antiplasmodial drug development.
SOUTH AFRICAN JOURNAL OF BOTANY
(2023)
Article
Biology
Oluwole Solomon Oladeji, Abimbola Peter Oluyori, Adewumi Oluwasogo Dada
Summary: Morinda lucida, a plant traditionally used to treat malaria in Nigeria, has shown antiplasmodial properties in this study. The leaves and bark of Morinda lucida could be potential sources for developing effective antimalarial drugs.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Nerea Escala, Laura M. Pineda, Michelle G. Ng, Lorena M. Coronado, Carmenza Spadafora, Esther del Olmo
Summary: Malaria cases and deaths remain high, mainly due to increased resistance to antimalarials. The search for new molecules to replace current drugs is essential. This study presents the synthesis of benzimidazole derivatives and evaluates their activity against P. falciparum HB3 strain. Compounds with electron donating groups on ring A and pyridine type structure on ring B show favorable activity. Two molecules display high nanomolar range antiplasmodial activity and selectivity indexes above 10. They seem to use a different pathway than chloroquine and most antimalarials.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Fidelia Ijeoma Uche, Xiaozhen Guo, Jude Okokon, Imran Ullah, Paul Horrocks, Joshua Boateng, Chenggang Huang, Wen-Wu Li
Summary: This study investigates the in vitro and in vivo antiplasmodial activities of BBIQ alkaloids and their analogues, showing promising results with significant anti-parasitic effects at low concentrations. Cycleanine and its semisynthetic analogues demonstrate improved potency and selectivity, with potential as leads for further drug development.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Medicinal
Phelelisiwe S. Dube, Lesetja J. Legoabe, Audrey Jordaan, Lester Sigauke, Digby F. Warner, Richard M. Beteck
Summary: Mycobacterium tuberculosis (Mtb) has an impermeable cell wall, making it resistant to many antibiotics. DprE1 is a crucial enzyme in Mtb cell wall synthesis, and has been identified as a target for potential tuberculosis drugs. PBTZ169 is the most promising DprE1 inhibitor, but more drug candidates are needed. By modifying the structure of PBTZ169, we synthesized 22 compounds and found that six of them exhibited sub-micromolar activity against Mtb. Compound 25 showed sub-micromolar activity against wild-type and fluoroquinolone-resistant Mtb strains.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Khalid Eljaaly, Asalah Helal, Tamather Almandeel, Rawan Algarni, Samah Alshehri
Summary: This study investigated the prevalence of drug-drug interactions between oral fluoroquinolones or tetracyclines with divalent or trivalent cation-containing compounds in hospitalized patients. The findings revealed a high prevalence of simultaneous administration of these antibiotics with polyvalent cations, indicating the need for antimicrobial stewardship programs to address this issue.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Infectious Diseases
Kasper Romer Villumsen, Toloe Allahghadry, Magdalena Karwanska, Joachim Frey, Anders Miki Bojesen
Summary: This study aims to describe the mechanisms of quinolone resistance in the pathogen Gallibacterium anatis. By analyzing the phenotypic and genomic data of a collection of G.anatis strains isolated from avian hosts between 1979 and 2020, several important sites related to quinolone resistance were identified. There were no notable structural differences between resistant and sensitive strains, suggesting that the resistance is likely due to subtle shifts in amino acid side chain properties.
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)
Article
Plant Sciences
Yoshihiro Watanabe, Kodai Hachiya, Akari Ikeda, Kenichi Nonaka, Mayuka Higo, Reiko Muramatsu, Chikako Noguchi, Masako Honsho, Yukihiro Asami, Yuki Inahashi, Tomoyasu Hirose, Hidehito Matsui, Toshiaki Sunazuka, Hideaki Hanaki, Takahiro Ishii, Toshiaki Teruya, Rei Hokari, Aki Ishiyama, Masato Iwatsuki
Summary: Two new antiplasmodial peptides, named koshida-cins A and B, were discovered from the culture broth of the Okinawan fungus Pochonia boninensis FKR-0564. Both compounds showed moderate in vitro antiplasmodial activity against Plasmodium falciparum strains, and compound 2 demonstrated significant suppression of malaria parasites in vivo.
JOURNAL OF NATURAL PRODUCTS
(2022)
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)