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
Vadims Kovada, Chrislaine Withers-Martinez, Raitis Bobrovs, Helena Cerule, Edgars Liepins, Solveiga Grinberga, Fiona Hackett, Christine R. R. Collins, Agrita Kreicberga, Maria Belen Jimenez-Diaz, Inigo Angulo-Barturen, Dace Rasina, Edgars Suna, Kristaps Jaudzems, Michael J. Blackman, Aigars Jirgensons
Summary: Researchers have developed a potential antimalarial drug by modifying an existing compound that inhibits the egress of Plasmodium falciparum, the causative agent of malaria. The improved compound showed enhanced inhibitory potency and stability compared to the original compound, as well as significant growth inhibition of the parasite. In animal models, the lead compound demonstrated dose-dependent clearance of blood-stage P. falciparum, highlighting its potential as an orally bioavailable drug for further development.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Plant Sciences
Catherine Nuwagira, Emanuel L. Peter, Clement Olusoji Ajayi, John Adriko, Grace-Rugunda Kagoro, Eunice Apio Olet, Patrick Engeu Ogwang, Casim Umba Tolo
Summary: The study aimed to investigate the effect of different developmental stages of S. pinnata on the antimalarial activity in mice, with results showing that extracts from the flowering stage had the best parasitemia suppression. Extracts from all developmental stages demonstrated a dose-dependent suppression of malarial parasites with an LD50 of 2157 mg/kg.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
James A. Ezugwu, Uchechukwu C. Okoro, Mercy A. Ezeokonkwo, Kurma S. Hariprasad, Mithun Rudrapal, David Ugwu, Neelutpal Gogoi, Dipak Chetia, Ismail Celik, Ogechi C. Ekoh
Summary: A new series of novel dipeptide sulfonamide analogues were designed and synthesized, and their in vitro and in vivo antimalarial activities were studied. The results showed significant antimalarial activity of these compounds. The in silico studies predicted high binding affinity of these compounds with the target proteins. The synthesized compounds exhibited drug-like properties, and their ADMET properties were within acceptable limits. Molecular dynamics simulation of the most active compound validated the stability of the protein-ligand complex and protein-ligand interactions.
Article
Chemistry, Medicinal
Dickson Mambwe, Constance M. Korkor, Amanda Mabhula, Zama Ngqumba, Cleavon Cloete, Malkeet Kumar, Paula Ladeia Barros, Meta Leshabane, Dina Coertzen, Dale Taylor, Liezl Gibhard, Mathew Njoroge, Nina Lawrence, Janette Reader, Diogo Rodrigo Moreira, Lyn-Marie Birkholtz, Sergio Wittlin, Timothy J. Egan, Kelly Chibale
Summary: Iterative medicinal chemistry optimization led to the discovery of a highly potent compound 23 with metabolic stability and selectivity, displaying activity against multiple stages of malaria and showing in vivo efficacy in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Parasitology
Shengwei Ji, Mingming Liu, Eloiza May Galon, Mohamed Abdo Rizk, Bumduuren Tuvshintulga, Jixu Li, Iqra Zafar, Yae Hasegawa, Aiko Iguchi, Naoaki Yokoyama, Xuenan Xuan
Summary: This study evaluated the in vitro and in vivo anti-Babesia activity of naphthoquine phosphate (NQP) and found that NQP showed promising therapeutic efficacy against Babesia infections.
PARASITES & VECTORS
(2022)
Article
Chemistry, Medicinal
A. Dassonville-Klimpt, J. Schneider, C. Damiani, C. Tisnerat, A. Cohen, N. Azas, M. Marchivie, J. Guillon, C. Mullie, P. Agnamey, Anne Totet, J. Dormoi, N. Taudon, B. Pradines, P. Sonnet
Summary: This study designed, synthesized, and evaluated five new series of aminoalcohol quinolines against Pf3D7 and PfW2 strains in vitro. Among the compounds, fourteen showed promising activity with IC50 values below or near 50.0 nM and high selectivity index. Compound 17b exhibited potent antimalarial activity with IC50 values of 14.9 nM and 11.0 nM against Pf3D7 and PfW2, respectively, and a high selectivity index. Further experiments and in vivo studies are needed to confirm its safety and efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Plant Sciences
Emmanuel O. Adeyoju, Clement O. Ajayi, Awodayo O. Adepiti, Anthony A. Elujoba
Summary: This study compared the antimalarial activity of methanol and water extracts of MAMA Powder against Plasmodium berghei-infected mice, finding that the water extract exhibited higher efficacy and can be optimized for chloroquine-resistant malaria, aiding in the production of various dosage forms.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Betelhem Sirak, Lea Mann, Adrian Richter, Kaleab Asres, Peter Imming
Summary: The leaves of Ranunculus multifidus Forsk. and its major constituent anemonin showed in vivo antimalarial activity against Plasmodium berghei in mice, with RM-H exhibiting superior activity. However, anemonin did not inhibit the growth of Mycobacterium smegmatis and M. abscessus.
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
Microbiology
Georges F. R. Radohery, Annabelle Walz, Christin Gumpp, Mohammed H. Cherkaoui-Rbati, Nathalie Gobeau, Jeremy Gower, Miles P. Davenport, Matthias Rottmann, James S. McCarthy, Jorg J. Mohrle, Maria Rebelo, Claudia Demarta-Gatsi, David S. Khoury
Summary: This study investigates the impact of artesunate on the viability of Plasmodium faciparum in humans and mice. The results show that artesunate leads to a faster decline in parasite viability compared to parasitemia. Higher concentrations of artesunate also result in faster parasite elimination. Predictions of infection recrudescence can be accurately made based on measures of parasite viability.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Infectious Diseases
Erik Koehne, Nina Zander, Miriam Rodi, Jana Held, Wolfgang Hoffmann, Rella Zoleko-Manego, Michael Ramharter, Ghyslain Mombo-Ngoma, Peter G. Kremsner, Andrea Kreidenweiss
Summary: The study results indicate that pyronaridine and methylene blue have potential for the treatment of schistosomiasis. Both drugs show certain efficacy against different physiological stages of schistosomes, with the combination drug pyronaridine-artesunate already demonstrating treatment potential in clinical settings.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Chemistry, Medicinal
Manvika Karnatak, Mohammad Hassam, Murugesan Vanangamudi, Siddharth Sharma, Dinesh Kumar Yadav, Chandan Singh, Sunil K. Puri, Varun Rawat, Ved Prakash Verma
Summary: A series of new compounds were synthesized and evaluated for their activity against multidrug-resistant Plasmodium, with one compound showing twice the activity of artemisinin. Additionally, the photooxygenation behavior of allylic alcohols was studied, revealing interesting outcomes regarding their conversion into corresponding trioxanes.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Microbiology
Silvia Parapini, Silvio Paone, Emanuela Erba, Loredana Cavicchini, Manoochehr Pourshaban, Francesco Celani, Alessandro Contini, Sarah D'Alessandro, Anna Olivieri
Summary: Malaria causes numerous cases and deaths annually, and the search for novel antimalarial drugs is essential. This study tested a series of Rac1 inhibitors and found that EHop-016 exhibited the most effective inhibitory activity against Plasmodium falciparum, without affecting red blood cell invasion but impacting parasite growth internally.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(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, Multidisciplinary
Linhu Li, Apeng Wang, Bin Wang, Mingliang Liu, Kai Lv, Zeyu Tao, Chao Ma, Xican Ma, Bing Han, Aoyu Wang, Yu Lu
CHINESE CHEMICAL LETTERS
(2020)
Article
Biochemistry & Molecular Biology
Kai Lv, Shuo Wu, Wenyan Li, Yunhe Geng, Meng Wu, Jinming Zhou, Yuhuan Li, Qiang Gao, Mingliang Liu
BIOORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Kai Lv, Wenyan Li, Shuo Wu, Yunhe Geng, Apeng Wang, Lu Yang, Menghao Huang, Kushan Chowdhury, Yuhuan Li, Mingliang Liu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Medicinal
Apeng Wang, Chao Ma, Yun Chai, Xiujun Liu, Kai Lv, Lei Fu, Bin Wang, Xuedong Jia, Mingliang Liu, Yu Lu
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Apeng Wang, Yu Lu, Kai Lv, Chao Ma, Shijie Xu, Bin Wang, Aoyu Wang, Guimin Xia, Mingliang Liu
BIOORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Apeng Wang, Shijie Xu, Yun Chai, Guimin Xia, Bin Wang, Kai Lv, Chao Ma, Dan Wang, Aoyu Wang, Xiaoyu Qin, Mingliang Liu, Yu Lu
Summary: A series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in the lab, were designed and synthesized as new anti-TB agents. Many compounds showed excellent in vitro activity against drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates, with good safety index. Compound 1o, in particular, displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its potential as a lead compound for future antitubercular drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Apeng Wang, Shijie Xu, Yun Chai, Guimin Xia, Bin Wang, Kai Lv, Dan Wang, Xiaoyu Qin, Bin Jiang, Wenhao Wu, Mingliang Liu, Yu Lu
Summary: The structure-activity relationship study of novel nitrofuran-1,3,4-oxadiazole hybrids as anti-TB agents showed that linkers and substituents greatly influence the activity, with substituted benzenes being more favored. The optimal compound in series 2 demonstrated strong activity against both MTB strains and low toxicity, indicating its potential as a lead compound for further development.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Aoyu Wang, Yuhuan Li, Kai Lv, Rongmei Gao, Apeng Wang, Haiyan Yan, Xiaoyu Qin, Shijie Xu, Chao Ma, Jiandong Jiang, Zengquan Wei, Kai Zhang, Mingliang Liu
Summary: JNJ4796, a small molecule fuse inhibitor, effectively neutralizes a broad spectrum of IAV and protects mice after oral administration. Compound (R)-2c shows excellent in vitro anti-IAV activity and low cytotoxicity, with a low inhibition rate of hERG.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Kai Lv, Shuo Wu, Zeyu Tao, Aoyu Wang, Shijie Xu, Lu Yang, Qiang Gao, Apeng Wang, Xiaoyu Qin, Bin Jiang, Wenhao Wu, Xuedong Jia, Yuhuan Li, Jiandong Jiang, Mingliang Liu
Summary: GYH2-18, a type II HBV CAM, was discovered to have anti-HBV activity. Derivatives of GYH2-18 were synthesized and evaluated, and compounds 2f and 3k showed excellent anti-HBV activity and low cytotoxicity. Chiral separation of 2f and 3k was successful, and (6S)-cyclopropyl DPPC isomers were found to be more active than the corresponding (6R)-ones.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiaoyu Qin, Lu Yang, Xican Ma, Bin Jiang, Shuo Wu, Apeng Wang, Shijie Xu, Wenhao Wu, Huijuan Song, Na Du, Kai Lv, Yuhuan Li, Mingliang Liu
Summary: RG7834, a DHQ candidate developed by Roche Pharma, was dismissed in phase I clinical trial due to its neurotoxicity. In this study, new DHQ derivatives containing a cyclic ether or benzo-fused ether moiety were designed, synthesized and evaluated for their in vitro activity. Many of them exhibited potent inhibition activity against HBV and showed potential improvement in neurotoxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Wenhao Wu, Haiyan Yan, Bin Jiang, Aoyu Wang, Xingqiong Li, Yuehao Zhang, Jizhou Wu, Xijun Zhong, Rongmei Gao, Apeng Wang, Kai Lv, Yuhuan Li, Mingliang Liu
Summary: This study describes the structure-activity relationship of the benzoxazole and tetrazole rings of JNJ4796. Many derivatives showed good in vitro activity against IAV H1N1 and Oseltamivir-resistant IAV H1N1 strains. Compound (R)-1a, identified in a previous study, displayed potent in vivo anti-IAV activity with survival rates comparable to JNJ4796.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Bo Wang, Yang Yang, Weixiao Wang, Jiaoyang Yu, Fengwan Zhang, Shuo Wu, Shijie Xu, Na Du, Xiaoyu Qin, Huijuan Song, Wenhao Wu, Bin Jiang, Mingliang Liu, Apeng Wang, Kai Lv, Wei Chen
Summary: In this study, a series of 3-nitrophenol ester derivatives were identified as promising quorum-sensing inhibitors through Structure-based Virtual Screening and structural optimization. Among them, 3-nitrophenol ester 1b showed potent LasR inhibition activity and low cytotoxicity. Molecular docking study revealed the formation of three intermolecular hydrogen bonds between 1b and the residues. Moreover, 1b was found to significantly inhibit the virulence of P. aeruginosa in vitro and in vivo, and transcriptome analysis indicated the inhibition of QS-related genes.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Xiaoyu Qin, Bin Jiang, Huijuan Song, Na Du, Yuehao Zhang, Xijun Zhong, Jizhou Wu, Tiezheng Xue, Mingliang Liu, Apeng Wang, Sanlong Wang, Kai Lv
Summary: In this study, the combination of quinolones and rifamycins was investigated to explore their potential against bacterial infections. Different substituents were incorporated into the N-(amino)piperazine moieties to enhance the anti-TB and antibacterial potency. Compounds 1k and 3e showed comparable activity to the reference drug, while compound 1d exhibited significantly higher potency against MRSA and VRE E.fm. These findings suggest the potential of compounds 1d and 1k as new leads for antibacterial and anti-TB drug development.
MEDICINAL CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Medicinal
Chongyi Ai, Zhuang Wang, Pengyun Li, Mengyuan Wang, Wenjuan Zhang, Huijuan Song, Xu Cai, Kai Lv, Xingjuan Chen, Zhibing Zheng
Summary: GSK-Bz, a TPRV4 antagonist discovered by GSK, showed potent TRPV4 inhibition activity and effectively inhibited TRPV4-mediated pulmonary edema in a rat model. In this study, a series of GSK-Bz derivatives were designed and synthesized. Compound 2b demonstrated superior potency compared to GSK-Bz, with enhanced inhibitory effects on TRPV4 currents and LPS permeability response. Additionally, 2b outperformed HC-067047 in protecting against acute lung injury in a mice model. These findings highlight the potential of 2b as a novel and highly potent TRPV4 antagonist for further development. Evaluation of the drug-like properties of 2b is currently underway.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xican Ma, Bing Han, Aoyu Wang, Lu Yang, Menghao Huang, Kushan Chowdhury, Jian Gu, Kai Zhang, Kai Lv
