4ytm › Citations

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

Scheme 1
Figure 1
Figure 2
Inaoka DK, Shiba T, Sato D, Balogun EO, Sasaki T, Nagahama M, Oda M, Matsuoka S, Ohmori J, Honma T, Inoue M, Kita K, Harada S
OpenAccess logo Int J Mol Sci 16 15287-308 (2015)
Related entries: 3abv, 3ae7, 3ae9, 3aea, 4ysx, 4ysy, 4ysz, 4yt0, 4ytp, 4yxd, 5c2t

Cited: 23 times
EuropePMC logo PMID: 26198225

Abstract

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Articles - 4ytm mentioned but not cited (5)

  1. Using C. elegans Forward and Reverse Genetics to Identify New Compounds with Anthelmintic Activity. Mathew MD, Mathew ND, Miller A, Simpson M, Au V, Garland S, Gestin M, Edgley ML, Flibotte S, Balgi A, Chiang J, Giaever G, Dean P, Tung A, Roberge M, Roskelley C, Forge T, Nislow C, Moerman D. PLoS Negl Trop Dis 10 e0005058 (2016)
  2. Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria. Inaoka DK, Shiba T, Sato D, Balogun EO, Sasaki T, Nagahama M, Oda M, Matsuoka S, Ohmori J, Honma T, Inoue M, Kita K, Harada S. Int J Mol Sci 16 15287-15308 (2015)
  3. Crystallographic investigation of the ubiquinone binding site of respiratory Complex II and its inhibitors. Huang LS, Lümmen P, Berry EA. Biochim Biophys Acta Proteins Proteom 1869 140679 (2021)
  4. The Open Form Inducer Approach for Structure-Based Drug Design. Inaoka DK, Iida M, Tabuchi T, Honma T, Lee N, Hashimoto S, Matsuoka S, Kuranaga T, Sato K, Shiba T, Sakamoto K, Balogun EO, Suzuki S, Nara T, Rocha JR, Montanari CA, Tanaka A, Inoue M, Kita K, Harada S. PLoS One 11 e0167078 (2016)
  5. Structure-Based Bioisosterism Design, Synthesis, Biological Evaluation and In Silico Studies of Benzamide Analogs as Potential Anthelmintics. Vairoletti F, Paulino M, Mahler G, Salinas G, Saiz C. Molecules 27 2659 (2022)


Reviews citing this publication (2)

  1. Why All the Fuss about Oxidative Phosphorylation (OXPHOS)? Xu Y, Xue D, Bankhead A, Neamati N. J Med Chem 63 14276-14307 (2020)
  2. An evolving view of complex II-noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Iverson TM, Singh PK, Cecchini G. J Biol Chem 299 104761 (2023)

Articles citing this publication (16)

  1. Mitochondrial protein interactome elucidated by chemical cross-linking mass spectrometry. Schweppe DK, Chavez JD, Lee CF, Caudal A, Kruse SE, Stuppard R, Marcinek DJ, Shadel GS, Tian R, Bruce JE. Proc Natl Acad Sci U S A 114 1732-1737 (2017)
  2. Integrating Cross-Linking Experiments with Ab Initio Protein-Protein Docking. Vreven T, Schweppe DK, Chavez JD, Weisbrod CR, Shibata S, Zheng C, Bruce JE, Weng Z. J Mol Biol 430 1814-1828 (2018)
  3. Ubiquinone binding site of yeast NADH dehydrogenase revealed by structures binding novel competitive- and mixed-type inhibitors. Yamashita T, Inaoka DK, Shiba T, Oohashi T, Iwata S, Yagi T, Kosaka H, Miyoshi H, Harada S, Kita K, Hirano K. Sci Rep 8 2427 (2018)
  4. In vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria. Suzuki S, Hikosaka K, Balogun EO, Komatsuya K, Niikura M, Kobayashi F, Takahashi K, Tanaka T, Nakajima M, Kita K. Antimicrob Agents Chemother 59 6960-6967 (2015)
  5. Novel Characteristics of Mitochondrial Electron Transport Chain from Eimeria tenella. Matsubayashi M, Inaoka DK, Komatsuya K, Hatta T, Kawahara F, Sakamoto K, Hikosaka K, Yamagishi J, Sasai K, Shiba T, Harada S, Tsuji N, Kita K. Genes (Basel) 10 E29 (2019)
  6. The ASCT/SCS cycle fuels mitochondrial ATP and acetate production in Trypanosoma brucei. Mochizuki K, Inaoka DK, Mazet M, Shiba T, Fukuda K, Kurasawa H, Millerioux Y, Boshart M, Balogun EO, Harada S, Hirayama K, Bringaud F, Kita K. Biochim Biophys Acta Bioenerg 1861 148283 (2020)
  7. The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a new Caenorhabditis elegans model. Saskői É, Hujber Z, Nyírő G, Likó I, Mátyási B, Petővári G, Mészáros K, Kovács AL, Patthy L, Supekar S, Fan H, Sváb G, Tretter L, Sarkar A, Nazir A, Sebestyén A, Patócs A, Mehta A, Takács-Vellai K. Dis Model Mech 13 dmm044925 (2020)
  8. Hypoxia Effects on Trypanosoma cruzi Epimastigotes Proliferation, Differentiation, and Energy Metabolism. Saraiva FMS, Cosentino-Gomes D, Inacio JDF, Almeida-Amaral EE, Louzada-Neto O, Rossini A, Nogueira NP, Meyer-Fernandes JR, Paes MC. Pathogens 11 897 (2022)
  9. Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection. Talaam KK, Inaoka DK, Hatta T, Tsubokawa D, Tsuji N, Wada M, Saimoto H, Kita K, Hamano S. Antimicrob Agents Chemother 65 e0041821 (2021)
  10. Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency. Lin S, Fasham J, Al-Hijawi F, Qutob N, Gunning A, Leslie JS, McGavin L, Ubeyratna N, Baker W, Zeid R, Turnpenny PD, Crosby AH, Baple EL, Khalaf-Nazzal R. Eur J Hum Genet 29 1570-1576 (2021)
  11. Dual inhibition of the Echinococcus multilocularis energy metabolism. Chaudhry S, Zurbriggen R, Preza M, Kämpfer T, Kaethner M, Memedovski R, Scorrano N, Hemphill A, Doggett JS, Lundström-Stadelmann B. Front Vet Sci 9 981664 (2022)
  12. Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics. Lautens MJ, Tan JH, Serrat X, Del Borrello S, Schertzberg MR, Fraser AG. PLoS Negl Trop Dis 15 e0009991 (2021)
  13. Mode of action of fluopyram in plant-parasitic nematodes. Schleker ASS, Rist M, Matera C, Damijonaitis A, Collienne U, Matsuoka K, Habash SS, Twelker K, Gutbrod O, Saalwächter C, Windau M, Matthiesen S, Stefanovska T, Scharwey M, Marx MT, Geibel S, Grundler FMW. Sci Rep 12 11954 (2022)
  14. Insecticidal activity of essential oils from American native plants against Aedes aegypti (Diptera: Culicidae): an introduction to their possible mechanism of action. Duque JE, Urbina DL, Vesga LC, Ortiz-Rodríguez LA, Vanegas TS, Stashenko EE, Mendez-Sanchez SC. Sci Rep 13 2989 (2023)
  15. Design, Synthesis, and Antifungal Activity of N-(alkoxy)-Diphenyl Ether Carboxamide Derivates as Novel Succinate Dehydrogenase Inhibitors. He B, Hu Y, Chen W, He X, Zhang E, Hu M, Zhang P, Yan W, Ye Y. Molecules 29 83 (2023)
  16. Killing Two Birds with One Stone: Discovery of Dual Inhibitors of Oxygen and Fumarate Respiration in Zoonotic Parasite, Echinococcus multilocularis. Enkai S, Kouguchi H, Inaoka DK, Shiba T, Hidaka M, Matsuyama H, Sakura T, Yagi K, Kita K. Antimicrob Agents Chemother 67 e0142822 (2023)


Quick links