			Home About us Contact

Useful Inhibitor (useful + inhibitor)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

Assessment of lovastatin application as tool in probing cytokinin-mediated cell cycle regulation

PHYSIOLOGIA PLANTARUM, Issue 2 2005
Katja Hartig
Lovastatin, a potent inhibitor of the mevalonate pathway, has been used in plant cell cycle studies to eliminate the cytosolic cytokinin biosynthesis. However, several implications can blur the results, as cytokinins may be alternatively formed from isopentenylpyrophosphate produced by the plastid 1-deoxy-xylulose 5-phosphate pathway and because the endogenous cytokinin levels oscillate considerably in the course of a cell cycle. In the work presented here, short- and long-term effects of lovastatin on suspension- cultured Nicotiana tabacum (L.) BY-2 cells were differentiated. The short-term experiments revealed a fast action of lovastatin, resulting in a significantly, though not completely, decreased content of endogenous cytokinins that became visible already after 10 min and was most pronounced after 30 min. But the impact of lovastatin on cell cycle progression depended also on the phase of the cell cycle at which it was administered. Lowering of the cytokinin level during the early S phase, when the endogenous cytokinin levels increased, delayed the S/G2 transition, whereas the same treatment in the late S phase, when the cellular cytokinin concentrations had already started to decrease, promoted it. Incubation periods longer than 48 h resulted in about 50% loss of viable of the cells and also in a reduced capability of division of the survivors. These cells later on resumed cell division. A second treatment with lovastatin of that culture again killed about 50% of the cells, but the surviving cells showed faster re-growth. In conclusion, lovastatin appears as a useful inhibitor of cytokinin biosynthesis in short-term studies, but its use in long-term experiments may create complex effects and therefore requires substantial caution. [source]

Inhibitory effects of Hoelen extract on melanogenesis in B16/F1 melanoma cells

PHYTOTHERAPY RESEARCH, Issue 9 2010
Mun Seog Chang
Abstract Melanin synthesis is regulated by melanogenic proteins, such as tyrosinase, tyrosinase-related protein 1 (TRP-1) and TRP-2. The effects of Hoelen extract on melanogenesis were investigated in B16Fl murine melanoma cells. Specifically, tyrosinase activity, cell viability and melanin content were assayed, and western blotting and RT-PCR for tyrosinase, TRP-1 and TRP-2 conducted. The results show that Hoelen significantly inhibited melanin synthesis through inhibition of TRP-2 expression, while it did not affect tyrosinase activity or its expression. Taken together, RT-PCR results showed that the depigmentation effect of Hoelen may be due to inhibition of TRP-2 gene transcription. These results suggest that Hoelen may be a useful inhibitor for the attenuation of melanogenesis and hyperpigmentation in skin cells. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Antibiotic Resistance in Bacteria: Novel Metalloenzyme Inhibitors

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2009
Sung-Kun Kim
,-Lactam antibiotics are among the most important drugs used to fight bacterial infection. Overuse and misuse of ,-lactam antibiotics has caused the evolution of resistance mechanisms, allowing pathogenic bacteria to survive antibiotic treatment. The major source of resistance to ,-lactam antibiotics occurs through production of enzymes called ,-lactamases capable of catalyzing hydrolysis of the ,-lactam rings in these drug compounds. The metallo-,-lactamases have become a major threat due to their broad substrate specificities; there are no clinically useful inhibitors for these metalloenzymes. We have obtained single-stranded DNA's that are potent inhibitors of the Bacillus cereus 5/B/6 metallo-,-lactamase. These are rapid, reversible, non-competitive inhibitors of the metalloenzyme, with Ki and Ki, values in the nanomolar range. The inhibition patterns and metal ion dependence of their inhibition suggest that the oligonucleotides alter the coordination of the active site metal ion(s); inhibition is efficient and highly specific. Microbiological growth experiments, using combinations of ssDNA with the ,-lactam antibiotic cephalexin, reveal that the inhibitor is capable of causing cell death in liquid cultures of both Gram-positive and Gram-negative metallo-,-lactamase producing bacteria in the micromolar concentration range. [source]

C6-Unsubstituted Pyrazolo[3,4- d]pyrimidines Are Dual Src/Abl Inhibitors Effective against Imatinib Mesylate Resistant Chronic Myeloid Leukemia Cell Lines

CHEMMEDCHEM, Issue 1 2009
Maria Alessandra Santucci Dr.
Abstract Docking simulations were used to predict the most favorable interaction between the T315I mutated form of Abl (invariably associated with resistance to the tyrosine kinase inhibitor imatinib mesylate, IM) and C6-unsubstituted and substituted pyrazolo[3,4- d]pyrimidines previously found to be dual Src/Abl inhibitors. Two C6-unsubstituted (1 and 2) and eight C6-substituted compounds (3,10) were selected and assayed for their effects on the Ba/F3 cell line transducing the wild-type p210Bcr,Abl construct, which is IM-sensitive, or three of the most common mutations associated with IM resistance in,vivo (T315I, Y253F, and E255K), and driven to drug resistance by saturating doses of IL-3 or by the expression of the Bcr,Abl construct coding for the p185 protein of acute lymphoblastic leukemia. Compounds 1 and 2 were active against all cell lines assayed (LD50 range: 0.7,4.3,,M), whereas C6-substituted compounds exhibited lower activity (LD50,8,,M for compound 3 toward the T315I mutant). Notably, 1 and 2 were also effective toward the T315I mutation, which is insensitive to dual Src/Abl inhibitors. The cytotoxic effects of 1 and 2 on IM-sensitive and IM-resistant Ba/F3 cells were attributable, at least in part, to their pro-apoptotic activity. Taken together, such findings suggest that C6-unsubstituted pyrazolo[3,4- d]pyrimidines may represent useful inhibitors to target IM-resistant chronic myeloid leukemia. [source]