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81.
Nihed Draoui Olivier Schicke Antony Fernandes Xavier Drozak Fady Nahra Amélie Dumont Jonathan Douxfils Emmanuel Hermans Jean-Michel Dogné Romu Corbau Arnaud Marchand Patrick Chaltin Pierre Sonveaux Olivier Feron Olivier Riant 《Bioorganic & medicinal chemistry》2013,21(22):7107-7117
Under hypoxia, cancer cells consume glucose and release lactate at a high rate. Lactate was recently documented to be recaptured by oxygenated cancer cells to fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate transporters (MCT) are the main lactate carriers and therefore represent potential therapeutic targets to limit cancer progression. In this study, we have developed and implemented a stepwise in vitro screening procedure on human cancer cells to identify new potent MCT inhibitors. Various 7-substituted carboxycoumarins and quinolinone derivatives were synthesized and pharmacologically evaluated. Most active compounds were obtained using a palladium-catalyzed Buchwald–Hartwig type coupling reaction, which proved to be a quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three log orders more active than the CHC reference compound. Comparison with warfarin, a conventional anticoagulant coumarin, further showed that compound 19 did not influence the prothrombin time which, together with a good in vitro ADME profile, supports the potential of this new family of compounds to act as anticancer drugs through inhibition of lactate flux. 相似文献
82.
83.
Gene and domain duplication in the chordate Otx gene family: insights from amphioxus Otx 总被引:5,自引:1,他引:5
We report the genomic organization and deduced protein sequence of a
cephalochordate member of the Otx homeobox gene family (AmphiOtx) and show
its probable single-copy state in the genome. We also present molecular
phylogenetic analysis indicating that there was single ancestral Otx gene
in the first chordates which was duplicated in the vertebrate lineage after
it had split from the lineage leading to the cephalochordates. Duplication
of a C-terminal protein domain has occurred specifically in the vertebrate
lineage, strengthening the case for a single Otx gene in an ancestral
chordate whose gene structure has been retained in an extant
cephalochordate. Comparative analysis of protein sequences and published
gene expression patterns suggest that the ancestral chordate Otx gene had
roles in patterning the anterior mesendoderm and central nervous system.
These roles were elaborated following Otx gene duplication in vertebrates,
accompanied by regulatory and structural divergence, particularly of Otx1
descendant genes.
相似文献
84.
Characterization of a Mycobacterium tuberculosis insertion sequence belonging to the IS3 family 总被引:33,自引:1,他引:32
R. A. McAdam † P. W. M. Hermans D. van Soolingen Z. F. Zainuddin ‡ D. Catty J. D. A. van Embden J. W. Dale 《Molecular microbiology》1990,4(9):1607-1613
A repetitive element (IS986), previously isolated from Mycobacterium tuberculosis and shown to detect multiple restriction fragment-length polymorphisms (RFLPs), has been sequenced. It consists of a potential insertion sequence of 1358bp, with 30-bp inverted repeat ends. IS986 has four potentially significant open reading frames (ORFs): ORFa1, ORFa2 and ORFb on one strand and ORFc on the complementary strand. The sequences of the potential translated products identify IS986 as a member of the IS3 family, with an apparent frameshift between ORFa1 and ORFa2. IS986 has potential as a highly specific probe for detection and typing of M. tuberculosis, as well as for transposon mutagenesis of mycobacteria. The sequence of IS986 is virtually identical to that of another recently described element, IS6110 (Thierry et al., 1990). 相似文献
85.
86.
Puspitasari Yunita Eka De Bruyne Tess Foubert Kenn Aulanni’am Aulanni’am Pieters Luc Hermans Nina Tuenter Emmy 《Phytochemistry Reviews》2022,21(4):1315-1358
Phytochemistry Reviews - Sea cucumbers or holothurians are marine invertebrates, belonging to the phylum Echinodermata (kingdom Animalia). In Asia, they are commonly used as food, while they are... 相似文献
87.
88.
Caymaris S Bootsma HJ Martin B Hermans PW Prudhomme M Claverys JP 《Molecular microbiology》2010,78(2):344-360
CodY is a global regulator highly conserved in low-G+C Gram-positive bacteria. It plays a key role in the adaptation of Bacillus subtilis to nutritional limitation through repression of a large gene set during exponential growth and relief of repression upon starvation. In several pathogenic bacteria, CodY regulates major virulence genes. Our interest in Streptococcus pneumoniae CodY originates from our observations that the oligopeptide permease Ami was involved in repression of competence for genetic transformation. We hypothesized that peptide uptake through Ami feeds amino acid pools, which are sensed by CodY to repress competence. As our initial attempts at inactivating codY failed, we launched an in-depth analysis into the question of the essentiality of codY. We report that codY cannot be inactivated unless a complementing ectopic copy is present. We obtained genetic evidence that a recently published D39 codY knock-out contains additional mutations allowing survival of codY mutant cells. Whole genome sequencing revealed mutations in fatC, which encodes a ferric iron permease, and amiC. This combination of mutations was confirmed to allow tolerance of codY inactivation. The amiC mutation is in itself sufficient to account for the strong derepression of competence development observed in D39 codY cells. 相似文献
89.
90.
François K. Chipeng Christian Hermans Giles Colinet Michel-Pierre Faucon Michel Ngongo Pierre Meerts Nathalie Verbruggen 《Plant and Soil》2010,328(1-2):235-244
Cu tolerance and accumulation have been studied in Haumaniastrum katangense, a cuprophyte from Katanga (DR Congo), previously described as a copper hyperaccumulator. Nicotiana plumbaginifolia, a well-known non-tolerant and non-accumulator species, was used as a control. The germination rate of H. katangense was enhanced by copper and fungicide addition, suggesting that fungal pathogens, which restrain germination in normal conditions, are limiting. In hydroponic culture in the Hoagland medium, H. katangense did not grow well, in contrast to N. plumbaginifolia. Better growth was achieved by adding fungicide or higher copper concentrations. The maximal non-effective concentration (NEC) was 12 µM CuSO4 for H. katangense grown in hydroponics, i.e. 24 times greater than Cu concentration in the Hoagland medium. By comparison, copper concentrations greater than 0.5 µM had a negative effect on the growth of N. plumbaginifolia. EC50 (50% effective concentration) in hydroponics was 40 µM CuSO4 for H. katangense and 6 µM CuSO4 for N. plumbaginifolia. EC100 (100% effective concentration) was 100 µM CuSO4 for H. katangense and 15 µM CuSO4 for N. plumbaginifolia. In soil, growth was also stimulated by Cu addition up to 300 mg kg-1 CuSO4. Surplus copper was also required for cultivating H. katangense in sterile conditions, suggesting that Cu excess may be necessary for needs other than pathogen defence. Cu accumulation in the shoot has been measured for N. plumbaginifolia and H. katangense at their respective NEC. Cu allocation in the two species showed a similar response to increasing Cu concentrations, i.e. root/shoot concentration ratio well above 1. In conclusion, H. katangense is highly tolerant to copper and has elevated copper requirement even in the absence of biotic interactions. Its accumulation pattern is typical of an excluder species. 相似文献