Structure-activity relationship of a novel antitumor ansamycin antibiotic trienomycin A and related compounds.

New Ansamycins from the Deep-Sea-Derived Bacterium Ochrobactrum sp. OUCMDZ-2164

“…for C 31 H 43 N 2 O 7 , 555.3065) (Figure S1), indicating 12 degrees of unsaturation. The UV spectrum of 1 showed similar absorptions with trienomycins at λ max 214, 254, 258, 272, and 284 nm [36]. The 1 H NMR spectrum (Table 1, Figure S2) showed three signals at δ H 6.30 (s), 6.43 (s), and 6.85 (s), as a result of a 1,3,5-trisubstituted benzene ring system.…”

“…The 13 C NMR revealed 31 carbon signals, which were classified by DEPT (distortionless enhancement by polarization transfer) and HSQC (heteronuclear single-quantum correlation) spectra as five methyl carbons (including a methoxy group), four methylene carbons, fifteen methine carbons (including 10 olefinic methine carbons), and seven quaternary carbons (including three carbonyls) (Table 1, Figures S3–S5). Analysis of 1 H and 13 C NMR data revealed that compound 1 shared the same ansamycin-like ring system as that of trienomycinol ( 3 ) [36], which was supported by the COSY (correlation spectroscopy) correlations of H-2/H-3/H-4/H-5/H-6/H-7/H-8/H-9/H-10/H-11/H-12/H-13, H-15/H-16/H-17, and H-12/H-24 (Figure S6), together with the key HMBC (heteronuclear multiple bond correlation) correlations of 3-OCH 3 to C-3, H-2 to C-1, H-24 to C-13, H-15 to C-13/C-14, H-17 to C-18/C-19/C-23, H-19 to C-21, H-23 to C-19, H-21 to C-19/C-23, and 20-NH to C-1/C-19/C-21 (Figure 2 and Figure S7). Careful comparison of the NMR data between 1 and 3 revealed observation of the signals of an N -acetylalanine in compound 1 , which was confirmed by the COSY correlation of H-2′/H-3′, and the HMBC correlations of H-2′ to C-1′/C-4′, 2′-NH to C-2′/C-4′, and H-5′ to C-4′ (Figure 2).…”

“…Additionally, HPLC profiling of these extracts indicated the presence of secondary metabolites with UV absorptions consistent with the ansamycins (λ max 214 and 272 nm). Chemical investigation led to the isolation of two new benzenic ansamycins, trienomycins H ( 1 ) and I ( 2 ), along with the known trienomycinol ( 3 ) [36,37] (Figure 1). The trienomycins A–F [29,38,39] possess different N -acyl substituted alanine ester moieties attached to C-11 of the ansamycin-like ring, such as cyclohexanecarboxyl, 3-methylbutanoyl, ( S )-2-methylbutanoyl, 1-cyclohexene-1-carboxyl, 4-methylpentanoyl, ( E )-3-pentenoyl, and ( E )-2-methyl-2-butenoyl, respectively, while the trienomycin G [21] is the isomer of trienomycin A by interchanging the position of 11- and 13- substituents.…”

SAR Study of a Novel Triene-ansamycin Group Compound, Quinotrierixin, and Related Compounds, as Inhibitors of ER Stress-induced XBP1 Activation

“…On the other hand, it was reported that OH group at C-19 and the double bonds at C-4, C-6, and C-8 were crucial for the inhibitory activity of mycotrienin II (11) against osteoclastic bone resorption [12]. Furthermore, it has been reported that OH group at C-13 of trienomycin A (12) was important for its cytocidal activity against HeLa S 3 cells [13], which is consistent with our findings that both 8 and 9 showed only weak their inhibitory activities against cell growth of HeLa cells (Table 3). There were many reports that triene-ansamycin group compounds showed antitumor effects in vitro and in vivo [6, 14ϳ16], however, underlying mechanisms for the inhibition of tumor growth by these compounds are unclear.…”

“…The active fractions were collected and further purified by preparative ODS HPLC (Sun Fire, 10 m m, 19ϫ250 mm, Waters Corp., USA) with 75% aq MeOH to give pure 1 (2.0 mg). The structure, the isolation procedure, the physico-chemical properties and the 13 C-NMR spectral data of 1 were shown in Figs. 1 and 2, Tables 1 and 2, respectively.…”