Cell growth substituent

Among the various substituents at the 6-position of the purine ring, only the fran5-(2-phenylcyclopropyl)amino derivative 196b consistently demonstrated inhibition of MT4 cell growth (vide supra 10 in Eq. (5), Sect. 2.4), Eq. (76) [263]. 

Other derivatives were synthesized where the 3 substituent was in turn an halide [14], a nitrogen quaternary salt-containing side chains [15], an O-alkylamine [15], a nitro group [15], an azido group [16], a functionalized C-2 unit [17]. Several fluorinated analogues of Combretastatins A-1 and A-4 were synthesized and their in vitro anticancer properties determined. The most active fluoro analogue 3 -deoxy-3 -fluoro-combretastatin A-4 retains the potent cell growth inhibitory properties of Combretastatin A-4 [14]. 

The effect of a series of 4-phenyl-5-(2/-Y, 4 -X, or 4/-X-cinnamoyl)-l,3,4-thiadiazolium-2-phenylamine chlorides was evaluated on B16-F10 murine melanoma cells in vitro and the tumors resulting from implanted B16-F10 cells in C57BL/6 mice. These compounds differ from each other only at the cinnamoyl ring substituent (42, X=N02 43, X=OH 44, X=F 45, X=Y=F). Upon exposure of B16-F10 cells to MI-D (42), 44, and 45, all of them at the same micromolar concentration (50 iM) decreased the cell viability to 8, 50, and 22%, respectively, while compound 43 did not show any significant effect under the same conditions. However, doses as low as 10 iM MI-D were sufficient to impair the cell growth over 72 h, but for 44 and 45 the effect on... 

Replacement of the A -methyl group of MTX by larger, more lipophilic substituents has been studied for its effects on DHFR binding, membrane transport, in vitro cell growth inhibition, and in vivo antitumour activity [14, 63-65]. 

Informations available on the role of the substituent on the nitrogen atom at 12-position are very limited. In fact, A/-desmethylacronycine (10) was the only compound modified at that position to be studied from a biological point of view. The inhibitory effect of 10. against HL-60 cell growth in vitro (IC50 = 17.6 pM) (42, 43) was of the same order of magnitude as that reported for acronycine itself. 

Bioactivity is determined by the ability of a material to invoke a crystallized carbonated apatite layer from a physiological fluid. Silica incorporation in HAp promotes early crystallization and a higher rate of osteoblastic cell proliferation on sintered materials. This response has not been isolated from the effects of different Ca/P ratio, surface area, and presence of other calcium phosphate phases (Best et al. 1997). Such comparative information on the influence of different substituent elements on the bioactivity still remains to be developed. In assessing the cell growth on apatites, it is... 

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