| InChI | InChI=1S/C27H45NO2.ClH/c1-16-7-12-27(28-15-16)17(2)24-23(30-27)14-22-20-6-5-18-13-19(29)8-10-25(18,3)21(20)9-11-26(22,24)4;/h16-24,28-29H,5-15H2,1-4H3;1H/t16-,17-,18-,19-,20+,21-,22-,23-,24-,25-,26-,27+;/m0./s1 |
| Reference | 1. Antimicrob Agents Chemother. 2011 May;55(5):1937-45. doi: 10.1128/AAC.01468-10.
Epub 2011 Feb 28. <br />
Tomatidine inhibits replication of Staphylococcus aureus small-colony variants in
cystic fibrosis airway epithelial cells. <br />
Mitchell G(1), Gattuso M, Grondin G, Marsault é, Bouarab K, Malouin F. <br />
Author information: <br />
(1)CEVDM, Université de Sherbrooke, Département de Biologie, Faculté des
Sciences, 2500 Boul. Université, Sherbrooke, Quebec, Canada, J1K2R1. <br />
Small-colony variants (SCVs) often are associated with chronic Staphylococcus
aureus infections, such as those encountered by cystic fibrosis (CF) patients. We
report here that tomatidine, the aglycon form of the plant secondary metabolite
tomatine, has a potent growth inhibitory activity against SCVs (MIC of 0.12
μg/ml), whereas the growth of normal S. aureus strains was not significantly
altered by tomatidine (MIC, >16 μg/ml). The specific action of tomatidine was
bacteriostatic for SCVs and was clearly associated with their dysfunctional
electron transport system, as the presence of the electron transport inhibitor
4-hydroxy-2-heptylquinoline-N-oxide (HQNO) caused normal S. aureus strains to
become susceptible to tomatidine. Inversely, the complementation of SCVs/’
respiratory deficiency conferred resistance to tomatidine. Tomatidine provoked a
general reduction of macromolecular biosynthesis but more specifically affected
the incorporation of radiolabeled leucine in proteins of HQNO-treated S. aureus
at a concentration corresponding to the MIC against SCVs. Furthermore, tomatidine
inhibited the intracellular replication of a clinical SCV in polarized CF-like
epithelial cells. Our results suggest that tomatidine eventually will find some
use in combination therapy with other traditional antibiotics to eliminate
persistent forms of S. aureus. <br />
2. FEBS Lett. 2008 Jul 9;582(16):2407-12. doi: 10.1016/j.febslet.2008.05.049. Epub
2008 Jun 9. <br />
Tomatidine inhibits iNOS and COX-2 through suppression of NF-kappaB and JNK
pathways in LPS-stimulated mouse macrophages. <br />
Chiu FL(1), Lin JK. <br />
Author information: <br />
(1)Institute of Biochemistry and Molecular Biology, College of Medicine, National
Taiwan University, No. 1 Section 1, Jen-ai Road, Taipei 10018, Taiwan. <br />
We use the LPS-stimulated macrophage as a model of inflammation to investigate
the anti-inflammatory effects of tomatidine and solasodine, whose structures
resemble glucocorticoids. We found that tomatidine exhibited a more potent
anti-inflammatory effect than solasodine. Tomatidine could decrease inducible
nitric oxide synthase and cyclooxygenase-2 expression through suppression of
I-kappaBalpha phosphorylation, NF-kappaB nuclear translocation and JNK
activation, which in turn inhibits c-jun phosphorylation and Oct-2 expression.
Here, we demonstrate that tomatidine acts as an anti-inflammatory agent by
blocking NF-kappaB and JNK signaling, and may possibly be developed as a useful
agent for the chemoprevention of cancer or inflammatory diseases. <br />
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