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para-Nitroblebbistatin

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para-Nitroblebbistatin
Names
IUPAC name (3aS)-3a-Hydroxy-6-methyl-1-(4-nitrophenyl)-2,3-dihydropyrroloquinolin-4-one
Other names
  • p-Nitroblebbistatin
  • (3aS)-1,2,3,3a-Tetrahydro-3a-hydroxy-6-methyl-1-(4-nitrophenyl)-4H-pyrroloquinolin-4-one
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
InChI
  • InChI=1S/C18H15N3O4/c1-11-2-7-15-14(10-11)16(22)18(23)8-9-20(17(18)19-15)12-3-5-13(6-4-12)21(24)25/h2-7,10,23H,8-9H2,1H3/t18-/m1/s1Key: KAUXNLHXGQGFOS-GOSISDBHSA-N
SMILES
  • CC1=CC2=C(C=C1)N=C3C(C2=O)(CCN3C4=CC=C(C=C4)(=O))O
Properties
Chemical formula C18H15N3O4
Molar mass 337.335 g·mol
Appearance Yellow solid
Solubility in water ~ 5 μM
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references
Chemical compound

para-Nitroblebbistatin is a non-phototoxic, photostable myosin inhibitor with low fluorescence. Its myosin inhibitory properties are very similar to those of blebbistatin.

Myosin specificity

Species Myosin type IC50
Rabbit Skeletal muscle myosin S1 0.4 μM, 0.1 μM
Dictyostelium discoideum Myosin II motor domain 2.3 μM, 9 μM
Human β-Cardiac myosin subfragment 1  13 μM
Chicken Heavy meromyosin fragment of skeletal muscle myosin  0.4 μM
Pig (left ventricle) cardiac myosin 3.9 μM
Chicken (gizzard) smooth muscle myosin S1 5.6 μM
Human (expressed in Sf9 cells) non-muscle myosin 2A / B / C motor domains 18 / 14 / 5 μM

Applications

para-Nitroblebbistatin has been successfully used in fluorescent imaging experiments involving myosin IIA-GFP expressing live dendritic cells and synaptophysin-pHluorin expressing live neurons.

References

  1. ^ Képiró, Miklós; Várkuti, Boglárka H.; Végner, László; Vörös, Gergely; Hegyi, György; Varga, Máté; Málnási-Csizmadia, András (2014-07-28). "para-Nitroblebbistatin, the non-cytotoxic and photostable myosin II inhibitor". Angewandte Chemie International Edition in English. 53 (31): 8211–8215. doi:10.1002/anie.201403540. ISSN 1521-3773. PMID 24954740.
  2. Rauscher, Anna Á.; Gyimesi, Máté; Kovács, Mihály; Málnási-Csizmadia, András (July 2018). "Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential". Trends in Biochemical Sciences. 43 (9): 700–713. doi:10.1016/j.tibs.2018.06.006. ISSN 0968-0004. PMID 30057142. S2CID 51864413.
  3. Roman, Bart I.; Verhasselt, Sigrid; Stevens, Christian V. (2018-06-21). "Medicinal Chemistry and Use of Myosin II Inhibitor (S)-Blebbistatin and Its Derivatives". Journal of Medicinal Chemistry. 61 (21): 9410–9428. doi:10.1021/acs.jmedchem.8b00503. ISSN 0022-2623. PMID 29878759. S2CID 46966833.
  4. Várkuti, Boglárka H.; Képiró, Miklós; Horváth, István Ádám; Végner, László; Ráti, Szilvia; Zsigmond, Áron; Hegyi, György; Lenkei, Zsolt; Varga, Máté (2016-05-31). "A highly soluble, non-phototoxic, non-fluorescent blebbistatin derivative". Scientific Reports. 6: 26141. Bibcode:2016NatSR...626141V. doi:10.1038/srep26141. ISSN 2045-2322. PMC 4886532. PMID 27241904.
  5. ^ in press: Gyimesi et al Improved inhibitory and ADMET properties of blebbistatin derivatives indicate that blebbistatin scaffold is ideal for drug development targeting myosin-2 in Journal of Pharmacology and Experimental Therapies (2020)
  6. ^ Tang, Wanjian; Blair, Cheavar A.; Walton, Shane D.; Málnási-Csizmadia, András; Campbell, Kenneth S.; Yengo, Christopher M. (2016). "Modulating Beta-Cardiac Myosin Function at the Molecular and Tissue Levels". Frontiers in Physiology. 7: 659. doi:10.3389/fphys.2016.00659. ISSN 1664-042X. PMC 5220080. PMID 28119616.
  7. Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël (2015-06-25). "Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells". Nature Communications. 6: 7526. Bibcode:2015NatCo...6.7526C. doi:10.1038/ncomms8526. ISSN 2041-1723. PMC 4491822. PMID 26109323.
  8. Soykan, Tolga; Kaempf, Natalie; Sakaba, Takeshi; Vollweiter, Dennis; Goerdeler, Felix; Puchkov, Dmytro; Kononenko, Natalia L.; Haucke, Volker (2017). "Synaptic Vesicle Endocytosis Occurs on Multiple Timescales and Is Mediated by Formin-Dependent Actin Assembly". Neuron. 93 (4): 854–866.e4. doi:10.1016/j.neuron.2017.02.011. PMID 28231467.
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