STRUCTURE-ACTIVITY RELATION IN CAMPTOTHECIN ANTITUMOR DRUGS - WHY A DETAILED MOLECULAR CHARACTERIZATION OF THEIR LACTONE AND CARBOXYLATE FORMS BY RAMAN AND SERS SPECTROSCOPIES

Lactone and carboxylate forms of potent antitumor agents, camptothecin s (CPTs) have been studied by Raman, Fourier-transform Raman (FT-Raman ) and surface-enhanced Raman scattering (SERS) spectroscopy. Similarit y of the Raman spectra of CPTs with corresponding FT-Raman spectra in the near-infrared allowed the latter to be compared with their SERS co unterparts in order to analyse the interaction of the drugs with silve r colloids. Different types of silver colloids (reduced with sodium bo rohydride or sodium citrate, with or without activation by anions) hav e been evaluated. Citrate-reduced colloid, activated with chloride ani ons (CAS) has been found to be the best compromise for SERS studies of both forms of CPTs. We suggest that in general CPTs are adsorbed on C AS via the nitrogen in ring B and are more inclined to a flat orientat ion than to a perpendicular one. However, probable interactions of sub stitution groups and/or of the COO- groups of hydrolysed CPTs with the CAS surface introduce some particularities in the adsorption patterns . As a result, SERS spectra are highly sensitive to hydrolysis and sub stitutions at distant rings of CPT and uniquely characteristic of each of the CPT derivatives. The pronounced hydrolysis-induced changes, si milar in the Raman and SERS spectra of CPTs, involve similar vibration s in the spectra of different CPTs. Vibrational assignments, proposed for the main Raman and SERS bands of CPT and its derivatives (21-lacta m-S-CPT, 10,11-(methylenedioxy)-CPT, CPT-11, SN-38 and topotecan) indi cate that most of the bands which decreased upon lactone hydrolysis ar e those preferentially related to stretching modes of the quinoline ri ngs A and B, and the bands which increased are those of the ring D str etching modes. Our data make the spectroscopic approach very promising for the further investigations of the molecular mechanisms of biologi cal activity of CPTs.