ABSTRACT
Purpose: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. Experimental design: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined in vivo observations with in vitro assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. Results: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response in vitro and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. Conclusion: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
ABSTRACT
In the title compound, C(24)H(36)O(4) [systematic name: (20S)-3ß-acet-oxy-16α-hydr-oxy-22,23-bis-nor-5α,17ß-cholano(22-16)lac-tone], the three six-membered rings adopt classical chair conformations, while the five-membered rings are in envelope conformations. The ester group attached to ring A is in an equatorial position. Rings A/B, B/C and C/D are trans-fused, whereas rings D/E are cis-fused. The structure is devoid of any classical hydrogen bonds. However, non-classical inter- and intra-molecular hydrogen-bonding inter-actions of the type C-Hâ¯O are present in the structure.
ABSTRACT
In the title compound, C(25)H(40)ClNO(3), prepared by the thermolysis of (20S)-O,N-diacetyl-20-amino-N-chloro-3ß-hydr-oxy-5α-pregnane, the three six-membered rings adopt chair conformations while the five-membered ring is in an envelope conformation. The ester group attached to ring A is in an equatorial position. All the rings are trans-fused. Intra-molecular C-Hâ¯O and C-Hâ¯Cl inter-actions occur. The crystal structure is stabilized by inter-molecular N-Hâ¯O and C-Hâ¯O inter-actions close contacts occur.
ABSTRACT
In the title mol-ecule {systematic name: (5S)-5-[(ß-d-gluco-pyranos-yloxy)meth-yl]furan-2(5H)-one}, C(11)H(16)O(8), the five-membered ring is essentially planar, the maximum deviation being 0.0151â (13)â Å for the O atom. The six-membered ring adopts a chair conformation with puckering parameters Q = 0.581â (2)â Å, θ = 9.0â (2)° and Ï = 39.7â (13)°, and with all of the substituents of the glucoside unit having normal equatorial orientations. The crystal structure is stabilized by extensive O-Hâ¯O and C-Hâ¯O hydrogen bonding, resulting in a three-dimensional network.
ABSTRACT
From Culcasia scandens P. Beauv., carota-4(5), 11(12)-diene (isodaucene), carota-3(4), 11(12)-dien-5-one, a new epoxide, 4,5-epoxy-carota-11(12)-ene (isodaucene epoxide) and beta-caryophyllene epoxide were isolated. The structures were established spectroscopically. Epoxidation of isodaucene with m-CPBA confirmed the structure and stereochemistry of the new epoxide.
Subject(s)
Araceae/chemistry , Sesquiterpenes/chemistry , Epoxy Compounds/chemistry , Molecular Structure , Polycyclic SesquiterpenesABSTRACT
The structure of the title compound, C23H35NO4, contains a unique pentacyclic ring system wherein one cyclohexyl ring adopts a chair conformation, two cyclohexyl rings are in boat conformations, and a six-membered heterocyclic ring and a cyclopentyl ring are in envelope conformations. The structures of the lycoctamones, alpha,beta-unsaturated aldehydes produced by acid-catalyzed degradation of lactams of lycoctonine-type alkaloids, previously deduced from the results of extensive chemical investigations have been proven to be correct by the determination of the crystal structure of this compound.
Subject(s)
Aconitine/analogs & derivatives , Alkaloids/chemistry , Aconitine/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Molecular Conformation , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Cytotoxic activity against the P388 cell line was seen in a crude extract of the New Zealand shrub Lophomyrtus bullata(Myrtaceae). Bioactivity-guided isolation led to a compound with NMR spectra complicated by the presence of two isomers. These crystallised together and an X-ray structure showed them to be stereoisomeric hybrids of triketone, phloroglucinol and bullatenone units. NMR measurements on the mixed isomers, as well as a cyclic ether produced from them by acid catalysed dehydration, were consistent with these structures. The natural products, named bullataketals A and B, have cytotoxic activity against the P388 cell line (IC(50) 1 microg ml(-1)), and antimicrobial activity against Bacillus subtilis.
