Antiproliferative activities

Synthesis and antiproliferative activity of furocoumarin isosters (pyrrolo-, thieno-, oxazolo-, and triazolocoumarins, 8- and 4- azapsoralenes) 95F479. 

The first SPRM to reach the advanced stage of clinical development for treatment of endometriosis and uterine fibroids, asoprisnil, is expected to receive FDA approval this year. The therapeutic effect of asoprisnil stems from its PR antagonist/ antiproliferative activity in the endometrium and breast. Unlike classical PR antagonists however, this compound does not induce labor in animal models of pregnancy and parturition. Recent structural studies... 

Dumoutier L, Tounsi A, Michiels T, Sommereyns C, Kotenko SV, Renauld JC (2004) Role of the interleukin (lL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of lL-29/interferon-lambda 1 similarities with type I interferon signaling. J Biol Chem 279 ... 

NASTRUZZI C, CORTESI R, ESPOSITO E, MENEGATTI E, LEONI O, lORI R and PALMIERI S (2000) In vitro antiproliferative activity of isothiocyanates and nitriles generated hy myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous vegetables , JAgric Food Chem, 48 3572-5. 

UGS1025A, a novel pentacyclic polyketide with an unprecedented furopyrrolizidine skeleton, 46 (Table 4) isolated from the fungus Acremorium sp. KY4917 exhibited antimicrobial and antiproliferative activity against human tumor cell lines. 

Soon afterwards [123] the bromo- (105) and iodo- (106) analogs of chlorovulone I (100) were also isolated from C. viridis in exceptionally low yield (ca. 0.01% of lipid extract). Their structures were established principally by spectroscopic means in comparison with chlorovulone I. Both of the new compounds possess the same olefin geometries as found in clavulone I and chlorovulone I. R Stereochemistry at Cl 2 was established in 105 by comparisons of CD spectra with those of chlorovulone I (100). These new halogenated clavulones showed levels of antiproliferative activity and cytotoxicity comparable to those of chlorovulone I (100). 

At about the same time, however, observation of strong antiproliferative activity in the CIO--11 epoxy analog of clavulone I (88) showed that the C10-11... 

Isoindolo[2,l-c]benzo[l,2,4]triazines 85 have been described as a new ring system with antiproliferative activity <06BMC343>. 

Meyers KJ, Watkins CB, Pritts MP and Liu RH. 2003. Antioxidant and antiproliferative activities of strawberries. J Agric Food Chem 51 6887-6892. 

Yang J, Meyers KJ, van der Heide J and Liu RH. 2004. Varietal differences in phenolic content and antioxidant and antiproliferative activities of onions. J Agric Food Chem 52 6787-6793. 

Not all type I interferons induce exactly the same range of responses, and the antiviral to antiproliferative activity ratio differs from one type I interferon to another. As all bind the same receptor, the molecular basis by which variation in biological activities is achieved is poorly understood as yet. 

Anthralin possesses antiproliferative activity on keratinocytes, inhibiting DNA synthesis by intercalation between DNA strands. 

The in vivo antitumor effects of interferons are believed to be related to both augmentation of natural killer cell activity and antiproliferative effects. Antiproliferative activity probably also accounts for the bone marrow suppression observed in some individuals given IFN and could potentially produce effects in a routine preclinical reproduction or teratology evaluation. Dosing studies performed in... 

Using BrdU pulse labelling was evident that at equivalent Gfio, compounds produced a delay in the S phase followed by an accumulation in G2/M, as is expected for mechanism of action of topi inhibitor. Antiproliferative activities was also found after shorter treatments as previously reported, when the duration of drug treatment was limited to 1 hour (Figure 6), at doses from 30 to 300 nM. 

A. R. Gagliardi, M. Kassack, A. Kremeyer, G. Muller, P. Nickel, and D. C. Collins. Antiangiogenic and antiproliferative activity of suramin analogues. Cancer Chemother. Pharmacol. 41 117-124 (1998). 

Over 300 peptides isolated in our laboratory were studied in one or more tumor or normal cell cultures [39-44]. Part of the results obtained is summarized in Table 2.3. Over 75% of the peptides showed pronounced proliferative or antiproliferative activity in at least one cell type (Fig. 2.3). As a rule, tumor cells are more sensitive to peptide action. Besides the cell type, experimental conditions such as cell density or composition of the culture medium also affected the overall effect. In several cases (13%, Fig. 2.3) even the sign of the effect was peptide concentration dependent. Generally, experiments with cell cultures conform with the view that the main physiological function of cell and tissue peptidomes is control of long term processes and the homeostatic balance (i.e. cell differentiation, proliferation and elimination). The overall effect of peptide pools is achieved by concerted action of total sets of peptides rather than by single components. The molecular mechanisms of peptide action in cells requires concrete study in each individual case and are the subject of current research. 

Bates PJ, Kahlon JB, Thomas SD, Trent JO, Miller DM (1999) Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J Biol Chem 274 26369-26377... 

Bergman AM, et al. Antiproliferative activity and mechanism of action of fatty acid derivatives of gemcitabine in leukemia and solid tumor cell lines and in human xenografts. Nucleosides Nucleotides Nucleic Acids 2004 23 1329. 

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