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New drugs have significantly improved the survival of patients with multiple myeloma (MM), but the prognosis of MM patients with high-risk cytogenetic changes such as t(4; 14), t(14; 16) or del17p remains very poor. A natural product, komaroviquinone (KQN), was originally isolated from the perennial semi-shrub Dracocephalum komarovi and has anti-protozoal activity against Trypanosoma cruzi, the organism causing Chagas' disease. Here we demonstrate that a novel KQN-derivative, GTN024, has an anti-MM effect both in vitro and in vivo. GTN024 induced the apoptosis of MM cell lines including those with high-risk cytogenetic changes. GTN024 produced reactive oxygen species (ROS) and increased phosphorylated eIF2α. The ROS production and subsequent endoplasmic reticulum (ER) stress are thought to play a key role in GTN024-induced apoptosis, as the apoptosis was completely abrogated by anti-oxidant treatment. In a mouse xenograft model, an intraperitoneal injection of 20 mg/kg of GTN024 significantly delayed tumor growth. Hematological toxicity and systemic toxicity as indicated by weight loss were not observed. These results suggest that the novel KQN-derivative GTN024 could become a candidate drug for treating high-risk MM., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this study isolation and structural elucidation of a homoisoflavonoid, 3-(3',4'-dihydroxybenzyl)-8-hydroxy-5,7-dimethoxychroman-4-one (Scillapersicone 1), is reported from Scilla persica HAUSSKN. The structure was solved by a single crystal X-ray analysis. The unit cell parameters are a=11.7676 (2)Å, b=20.1174 (4)Å, c=7.8645 (9)Å, β=93.544 (2)°, V=1858.23 (7)Å(3), monoclinic space group P21/c and four symmetry equivalent molecules in an unit cell. The structure was consistent with the UV, IR, 1D and 2D NMR, HRFAB-MS data. The optimized molecular geometry agrees closely that obtained from the single crystal X-ray crystallography. Furthermore, cytotoxicity of this compound was evaluated by MTT assay on AGS and WEHI-164 cancerous cell lines., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Stereocontrolled syntheses of three neutral glycosphingolipids and six oligosaccharide derivatives found from the parasite Schistosoma mansoni have been accomplished. A pentasaccharide glycosphingolipid β-D-Galp-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAc-(1→3)-β-D-GalpNAc-(1→4)-β-D-Glcp-(1↔1)-Cer (1), two hexasaccharide glycosphingolipids α-L-Fucp-(1→3)-β-D-Galp-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAc-(1→3)-β-D-GalpNAc-(1→4)-β-D-Glcp-(1↔1)-Cer (2) and β-D-Galp-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAc-(1→3)-β-D-GlcpNAc-(1→3)-β-D-GalpNAc-(1→4)-β-D-Glcp-(1↔1)-Cer (3), together with their non-reducing end tri- and tetrasaccharides, β-D-Galp-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (4) and α-L-Fucp-(1→3)-β-D-Galp-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (5), were synthesized by block synthesis. Moreover, non-reducing end oligosaccharides of schistosomal glycosphingolipids, β-D-GalpNAc-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (6), α-L-Fucp-(1→3)-β-D-GalpNAc-(1→4)-[α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (7), α-L-Fucp-(1→3)-β-D-GalpNAc-(1→4)-[α-L-Fucp-(1→2)-α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (8) and α-L-Fucp-(1→3)-β-D-GalpNAc-(1→4)-[α-L-Fucp-(1→2)-α-L-Fucp-(1→2)-α-L-Fucp-(1→3)]-β-D-GlcpNAcOR (9) [R=2-(trimethylsilyl)ethyl], were synthesized as probes to explore their diagnostic potential to detect schistosomiasis from patients' sera., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Vitamin B12 is synthesized by many different organisms, for example Pseudomonas denitrificans (aerobic) and Propionibacterium shermanii ('microaerophilic', or essentially anaerobic). The biosynthetic pathways in these two organisms show strong similarities but also some differences. There have been conflicting reports on where differences between these two organisms lie in the stages beyond the formation of the corrin macrocycle. Characterization of intermediates in the pathway will help resolve these conflicts., Results: A single cobyrinic acid diamide and a single triamide have been isolated from Pr. shermanii. The diamide was shown to be the a,c-isomer. The triamide is not the a,c,g-isomer but it is indistinguishable from the single triamide isolated by other workers from Ps. denitrificans. The Co-(5'-deoxy-5'-adenosyl) derivative of the a,c-diamide was also isolated and fully characterized and the deoxyadenosyl derivative of the foregoing triamide has been shown to be present in the cells., Conclusions: Our results support a unique pathway in Pr. shermanii proceeding from cobyrinic acid towards coenzyme B12, at least as far as the adenosylated triamide intermediate. No evidence was found for multiple alternative pathways. The order of amidations of the carboxyl side-chains of cobyrinic acid up to the triamide stage is the same in Pr. shermanii and Ps. denitrificans.