Azamollugin, a mollugin derivative, has inhibitory activity on MyD88- and TRIF-dependent pathways

Itokawa H, Qiao Y, Takeya K (1989) Anthraquinones and naphthohydroquinones from Rubia cordifolia. Phytochemistry 28:3465–3468

Article  CAS  Google Scholar 

Itokawa H, Mihara K, Takeya K (1983) Studies on a novel anthraquinone and its glycosides isolated from Rubia cordifolia and R. akane. Chem Pharm Bull 31:2353–2358

Article  CAS  Google Scholar 

Kawasaki Y, Goda Y, Yoshihira K (1992) The mutagenic constituents of Rubia tinctorum. Chem Pharm Bull 40:1504–1509

Article  CAS  Google Scholar 

Dosseh C, Tessier AM, Delaveau P (1981) Rubia cordifolia roots. II: New quinones. Planta Med 43:141–147

Article  CAS  PubMed  Google Scholar 

Wang SX, Hua HM, Wu LJ, Li X, Zhu TR (1992) Studies on anthraquinones from the roots of Rubia cordifolia L. Acta Pharm Sin 27:743–747

CAS  Google Scholar 

Lee JE, Hitotsuyanagi Y, Kim IH, Hasuda T, Takeya K (2008) A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: Structure, semisynthesis, and cytotoxicity. Bioorg Med Chem Lett 18:808–811

Article  CAS  PubMed  Google Scholar 

Hitotsuyanagi Y, Hasuda T, Aihara T, Ishikawa H, Yamaguchi K, Itokawa H, Takeya K (2004) Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-containing analogues of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants. J Org Chem 69:1481–1486

Article  CAS  PubMed  Google Scholar 

Hitotsuyanagi Y, Hirai M, Odagiri M, Komine M, Hasuda T, Fukaya H, Takeya K (2019) RA-XXV and RA-XXVI, bicyclic hexapeptides from Rubia cordifolia L.: Structure, synthesis, and conformation. Chem Asian J 14:205–215

Article  CAS  PubMed  Google Scholar 

Hitotsuyanagi Y, Odagiri M, Kato S, Kusano J, Hasuda T, Fukaya H, Takeya K (2012) Isolation, structure determination, and synthesis of allo-RA-V and neo-RAV, RA-series bicyclic peptides from Rubia cordifolia L. Chemistry 18:2839–2846

Article  CAS  PubMed  Google Scholar 

Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM (1996) Inhibition of Hepatitis B surface antigen secretion on human hepatoma cells. components from Rubia cordifolia. J Nat Prod 59:330–333

Article  CAS  PubMed  Google Scholar 

Itokawa H, Ibraheim Z, Qiao Y, Takeya K (1993) Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull 41:1869–1872

Article  CAS  Google Scholar 

Son JK, Jung SJ, Jung JH, Fang Z, Lee CS, Seo CS, Moon DC, Min BS, Kim MR, Woo MH (2008) Anticancer constituents from the roots of Rubia cordifolia L. Chem Pharm Bull 56:213–216

Article  CAS  Google Scholar 

Kim KJ, Lee JS, Kwak MK, Choi HG, Yong CS, Kim JA, Lee YR, Lyoo WS, Park Y-J (2009) Anti-inflammatory action of mollugin and its synthetic derivatives in HT-29 human colonic epithelial cells is mediated through inhibition of NF-κB activation. Eur J Pharmacol 622:52–57

Article  CAS  PubMed  Google Scholar 

Jeong GS, Lee DS, Kim DC, Jahng Y, Son JK, Lee SH, Kim YC (2011) Neuroprotective and anti-inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells. Eur J Pharmacol 654:226–234

Article  CAS  PubMed  Google Scholar 

Zhu ZG, Jin H, Yu PJ, Tian YX, Zhang JJ, Wu SG (2013) Mollugin inhibits the inflammatory response in lipopolysaccharide-stimulated RAW264.7 macrophages by blocking the janus kinase-signal transducers and activators of transcription signaling pathway. Biol Pharm Bull 36:399–406

Article  CAS  PubMed  Google Scholar 

Do MT, Hwang YP, Kim HG, Na M, Jeong HG (2013) Mollugin inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing cancer cells. J Cell Physio 228:1087–1097

Article  CAS  Google Scholar 

Zhang L, Wang H, Zhu J, Xu J, Ding K (2014) Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6 K and ERK signaling pathways. Biochem Biophys Res Commun 450:247–254

Article  CAS  PubMed  Google Scholar 

Baek JM, Kim JY, Jung Y, Moon SH, Choi MK, Kim SH, Lee MS, Kim I, Oh J (2015) Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo. Phytomedicine 22:27–35

Article  CAS  PubMed  Google Scholar 

Han L, Yong FL, Hong Z, Jiang MH, Hong ML, Shou JL (2021) synthesis and antitumor activity of 1-substituted 1,2,3-Triazole-Mollugin derivatives. Molecules 26:3249

Article  Google Scholar 

Zhang LH, Li MY, Wang DY, Jin XJ, Chen FE, Piao HR (2022) synthesis and evaluation of NF-κB inhibitory activity of Mollugin derivatives. Molecules 27:7925

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morita H, Nishino H, Nakajima Y, Kakubari Y, Nakata A, Deguchi J, Alfarius EN, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y (2015) Oxomollugin, a potential inhibitor of lipopolysaccharide-induced nitric oxide production including nuclear factor kappa B signals. J Nat Med 69:608–611

Article  CAS  PubMed  Google Scholar 

Nakajima Y, Tsuboi N, Katori K, Waili M, Nugroho AE, Takahashi K, Nishino H, Hirasawa Y, Kawasaki Y, Goda Y, Kaneda T, Morita H (2024) Oxomollugin, an oxidized substance in mollugin, inhibited LPS-induced NF-κB activation via the suppressive effects on essential activation factors of TLR4 signaling. J Nat Med 78:568–575

Article  CAS  PubMed  Google Scholar 

Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384

Article  CAS  PubMed  Google Scholar 

Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K (2008) Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling. Brioche Biophys Res Commun 368:94–99

Article  CAS  Google Scholar 

Nishino H, Nakajima Y, Kakubari Y, Asami N, Deguchi J, Nugroho AE, Hirasawa Y, Kaneda T, Kawasaki Y, Goda Y, Morita H (2016) Syntheses and anti-inflammatory activity of azamollugin derivatives. Bioorg Med Chem Lett 26:524–525

Article  CAS  PubMed  Google Scholar 

Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T (2006) Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5:749–757

Article  CAS  PubMed  Google Scholar 

Hatti I, Sreenivasulu R, Jadav S, Jayaprakash V, Kumar CG, Raju R (2015) Synthesis, cytotoxic activity and docking studies of new 4-aza-podophyllotoxin derivatives. Med Chem Res 24:3305–3313

Article  CAS  Google Scholar 

Hitotsuyanagi Y, Fukuyo M, Tsuda K, Kobayashi M, Ozeki A, Itokawa H, Takeya K (2000) 4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity. Bioorg Med Chem Lett 10:315–317

Article  CAS  PubMed  Google Scholar 

Le Nguyen T, De Borggraeve WM, Grellier P, Pham VC, Dehaen W, Nguyen VH (2014) Synthesis of 11-aza-artemisinin derivatives using the Ugi reaction and an evaluation of their antimalarial activity. Tetrahedron Lett 55:4892–4894

Article  Google Scholar 

Fujita Y, Islam R, Sakai K, Kaneda H, Kudo K, Tamura D, Aomatsu K, Nagai T, Kimura H, Matsumoto K, de Velasco M, Arao T, Okawara T, Nishio K (2012) Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors. Invest New Drugs 30:1878–1886

Article  CAS  PubMed  Google Scholar 

Kawaii S, Endo K, Tokiwano T, Yoshizawa Y (2012) Relationship between structure and antiproliferative activity of 1-azaflavanones. Anticancer Res 32:2819–2825

CAS  PubMed  Google Scholar 

Kleinert H, Pautz A, Linker K, Schwarz PM (2004) Regulation of the expression of inducible nitric oxide synthase. Eur J Pharmacol 500:255–266

Article  CAS  PubMed 

Comments (0)

No login
gif