In vitro activity of novel sulphonic derivatives of distamycin A.

The successful growth of tumors is dependent on the process of vascularization elicited by the tumor itself. As confirmed by many authors, there is a correlation between the presence of factors that stimulate tumor growth and angiogenesis. One of the approaches we have explored to control angiogenesis has been to synthesize compounds able to complex growth factors. A number of sulphonated derivatives of distamycin A were found active in inhibiting the binding of bFGF and PDGF beta on Swiss 3T3 cells with ID50 values ranging between 142-587 microM for bFGF and 28-79 microM for PDGF beta. The effect of these new derivatives in inhibiting angiogenesis was initially explored in the chorioallantoic membrane assay. It was observed that the selected compounds were active in this model system at the concentration of 350 nm/pellet. These new molecules present low or no cytotoxic activity on M5076 murine reticulosarcoma cells, the ID50 values being higher than 60 microM after 72 h continuous exposure in vitro.

Solid-supported benzotriazoles. 2. Synthetic auxiliaries and traceless linkers for the combinatorial synthesis of unsymmetrical ureas.

Resin-bound benzotriazole chemistry applied to the solid-phase synthesis of arrays of unsymmetrical aryl ureas is described here. The chemistry assessment process, the monomer rehearsal, the preparation of a discrete library by automated parallel synthesis, the parallel purification protocol employing solid-phase scavenging, and the complete analytical characterization of the library components are also presented.

A combinatorial approach to [1,5]benzothiazepine derivates as potential antibacterial agents.

[1,5]Benzothiazepines are widely used in a number of different therapeutic areas and therefore represent an interesting scaffold for de novo exploration. Recent literature reports suggest their value as antibacterial agents. The present paper reports the exploration of this scaffold for the generation of combinatorial libraries both in solution and on solid phase.

Dansyl and dabsyl analytical constructs as tools for the accurate estimation of compounds in solid-phase synthesis.

The presence of dansyl or dabsyl chromogenic moieties in a solid-phase analytical construct, an assembly of linkers/spacers/sensitizers for improving analytical characterization, allows the accurate estimation of products from solid-phase synthesis by UV detection during liquid chromatography-mass spectrometry analysis in the cleavage solution. The spectroscopic properties of dansylated molecules have been evaluated to verify the "compound-independent UV absorption" necessary for using the chromophore in the accurate estimation. First, measurements on commercial dansylated compounds were made, then a series of construct-like molecules were prepared by solution-phase synthetic procedures and their UV properties were determined. Compound calibration curves were determined, and UV absorption was shown to be both proportional to the compound concentration and compound-independent. An example of a dansyl construct derivative was then prepared on a polymeric matrix, and an accurate estimation using the calibration curves was carried out in the cleavage solution. Good agreement was found between the calculated amount of released compound using the UV calibration curves and the calculated amount using both (1)H NMR and LC/chemiluminescent nitrogen detection quantitative techniques. Preliminary studies using the dabsyl moiety as an improved chromophore with higher wavelength and extinction coefficient are also reported.