Design, synthesis, and biological evaluation of multiple targeting antimalarials

Acta Pharmaceutica Sinica B - Tập 11 - Trang 2900-2913 - 2021
Yiqing Yang1, Tongke Tang2,3, Xiaolu Li4, Thomas Michel5, Liqin Ling6,7, Zhenghui Huang2,8, Maruthi Mulaka6, Yue Wu1, Hongying Gao1, Liguo Wang1, Jing Zhou7, Brigitte Meunier5, Hangjun Ke6, Lubin Jiang2,8, Yu Rao1
1MOE Key Laboratory of Protein Sciences, School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical Biology, Tsinghua University, Beijing 100084, China
2Unit of Human Parasite Molecular and Cell Biology, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
3School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
4Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China
5Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Saclay, Gif-sur-Yvette 91198, France
6Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA
7Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
8The Nanjing Unicorn Academy of Innovation, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Nanjing 211135, China

Tài liệu tham khảo

2020 Cheviet, 2019, Plasmodium purine metabolism and its inhibition by nucleoside and nucleotide analogues, J Med Chem, 62, 8365, 10.1021/acs.jmedchem.9b00182 Blasco, 2017, Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic, Nat Med, 23, 917, 10.1038/nm.4381 Amato, 2018, Origins of the current outbreak of multidrug-resistant malaria in Southeast Asia: a retrospective genetic study, Lancet Infect Dis, 18, 337, 10.1016/S1473-3099(18)30068-9 Uwimana, 2020, Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda, Nat Med, 26, 1602, 10.1038/s41591-020-1005-2 Goodman, 2017, Is the mitochondrion a good malaria drug target?., Trends Parasitol, 33, 185, 10.1016/j.pt.2016.10.002 Stocks, 2014, Novel inhibitors of the Plasmodium falciparum electron transport chain, Parasitology, 141, 50, 10.1017/S0031182013001571 Painter, 2007, Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum, Nature, 446, 88, 10.1038/nature05572 Leung, 2012, Identification, design and biological evaluation of heterocyclic quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2), J Med Chem, 55, 1844, 10.1021/jm201184h Yang, 2017, Target elucidation by cocrystal structures of NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) with small molecule to eliminate drug-resistant malaria, J Med Chem, 60, 1994, 10.1021/acs.jmedchem.6b01733 Petri, 2018, Structure of the NDH-2‒HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors, Biochim Biophys Acta Bioenerg, 1859, 482, 10.1016/j.bbabio.2018.03.014 Birth, 2014, Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action, Nat Commun, 5, 4029, 10.1038/ncomms5029 Lane, 2018, Selection of Plasmodium falciparum cytochrome B mutants by putative PfNDH2 inhibitors, Proc Natl Acad Sci U S A, 115, 6285, 10.1073/pnas.1804492115 Capper, 2015, Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1, Proc Natl Acad Sci U S A, 112, 755, 10.1073/pnas.1416611112 Stickles, 2016, Atovaquone and ELQ-300 combination therapy as a novel dual-site cytochrome bc1 inhibition strategy for malaria, Antimicrob Agents Chemother, 60, 4853, 10.1128/AAC.00791-16 David, 2018, Potent antimalarial 2-pyrazolyl quinolone bc1 (Qi) inhibitors with improved drug-like properties, ACS Med Chem Lett, 9, 1205, 10.1021/acsmedchemlett.8b00371 Llanos-Cuentas, 2018, Antimalarial activity of single-dose DSM265, a novel plasmodium dihydroorotate dehydrogenase inhibitor, in patients with uncomplicated Plasmodium falciparum or Plasmodium vivax malaria infection: a proof-of-concept, open-label, phase 2a study, Lancet Infect Dis, 18, 874, 10.1016/S1473-3099(18)30309-8 Mandt, 2019, In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model, Sci Transl Med, 11, 10.1126/scitranslmed.aav1636 Yang, 2019, Discovery, optimization, and target identification of novel potent broad-spectrum antiviral inhibitors, J Med Chem, 62, 4056, 10.1021/acs.jmedchem.9b00091 Xu, 2013, Novel selective and potent inhibitors of malaria parasite dihydroorotate dehydrogenase: discovery and optimization of dihydrothiophenone derivatives, J Med Chem, 56, 7911, 10.1021/jm400938g Ke, 2019, Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages, PLoS One, 14, 10.1371/journal.pone.0214023 Paton, 2019, Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission, Nature, 567, 239, 10.1038/s41586-019-0973-1 Boysen, 2011, Arrested oocyst maturation in Plasmodium parasites lacking type II NADH:ubiquinone dehydrogenase, J Biol Chem, 286, 32661, 10.1074/jbc.M111.269399 Biagini, 2012, Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria, Proc Natl Acad Sci U S A, 109, 8298, 10.1073/pnas.1205651109 Song, 2018, The antimalarial compound ELQ-400 is an unusual inhibitor of the bc1 complex, targeting both Qo and Qi sites, FEBS Lett, 592, 1346, 10.1002/1873-3468.13035 Feng, 2012, Structural insight into the type-II mitochondrial NADH dehydrogenases, Nature, 491, 478, 10.1038/nature11541 Leslie, 2007, Novel carbazole derivatives as NPY Y1 antagonists, Bioorg Med Chem Lett, 17, 1043, 10.1016/j.bmcl.2006.11.034 Pegoraro, 2017, SC83288 is a clinical development candidate for the treatment of severe malaria, Nat Commun, 8, 14193, 10.1038/ncomms14193 Mu, 2010, Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs, Nat Genet, 42, 268, 10.1038/ng.528 Kato, 2016, Diversity-oriented synthesis yields novel multistage antimalarial inhibitors, Nature, 538, 344, 10.1038/nature19804 Ke, 2011, Variation among Plasmodium falciparum strains in their reliance on mitochondrial electron transport chain function, Eukaryot Cell, 10, 1053, 10.1128/EC.05049-11 Wang, 2015, Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum, Nat Commun, 6, 10111, 10.1038/ncomms10111 Ismail, 2016, Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7, Proc Natl Acad Sci U S A, 113, 2080, 10.1073/pnas.1600459113 Vallières, 2013, Reconstructing the Qo site of Plasmodium falciparum bc1 complex in the yeast enzyme, PLoS One, 8, 10.1371/journal.pone.0071726 Song, 2015, Interplay between the hinge region of iron sulphur protein and the Qo site in the bc1 complex analysis of Plasmodium-like mutations in the yeast enzyme, Biochim Biophys Acta, 1847, 1487, 10.1016/j.bbabio.2015.08.005 Lencina, 2018, Type 2 NADH dehydrogenase is the only point of entry for electrons into the Streptococcus agalactiae respiratory chain and is a potential drug target, mBio, 9, 10.1128/mBio.01034-18 Lin, 2011, Two internal type II NADH dehydrogenases of Toxoplasma gondii are both required for optimal tachyzoite growth, Mol Microbiol, 82, 209, 10.1111/j.1365-2958.2011.07807.x Sellamuthu, 2017, Type-II NADH dehydrogenase (NDH-2): a promising therapeutic target for antitubercular and antibacterial drug discovery, Expert Opin Ther Targets, 21, 559, 10.1080/14728222.2017.1327577 Modica-Napolitano, 2001, Delocalized lipophilic cations selectively target the mitochondria of carcinoma cells, Adv Drug Deliv Rev, 49, 63, 10.1016/S0169-409X(01)00125-9 Shi, 2019, Gboxin is an oxidative phosphorylation inhibitor that targets glioblastoma, Nature, 567, 341, 10.1038/s41586-019-0993-x Hill, 2003, Recapitulation in Saccharomyces cerevisiae of cytochrome b mutations conferring resistance to atovaquone in Pneumocystis jiroveci, Antimicrob Agents Chemother, 47, 2725, 10.1128/AAC.47.9.2725-2731.2003 Lemaire, 2008, Preparation of respiratory chain complexes from Saccharomyces cerevisiae wild-type and mutant mitochondria: activity measurement and subunit composition analysis, Methods Mol Biol, 432, 65, 10.1007/978-1-59745-028-7_5 Ke, 2018, The mitochondrial ribosomal protein L13 is critical for the structural and functional integrity of the mitochondrion in Plasmodium falciparum, J Biol Chem, 293, 8128, 10.1074/jbc.RA118.002552 Bowers, 2006, Scalable algorithms for molecular dynamics simulations on commodity clusters