Evaluation of novel platinum , and platinum ammine/amine complexes in L1210 murine leukaemia cell lines sensitive and resistant to cisplatin and tetraplatin
Orr, R.M.; Barnard, C.F.J.; Murrer, B.A.; O'neill, C.F.; Nicolson, M.C.; Balazova, E.; Harrap, K.R.
Cellular Pharmacology 1(1): 17-23
1993
Accession: 031324053
L1210 variants with acquired resistance to cisplatin (tenfold, L1210/cis) or tetraplatin (34-fold, L1210/tetra) were developed from a parent sensitive line (L1210/S) and the chemosensitivity profiles characterised. These lines were used to screen four series of platinum-containing ammine/amines based broadly on the structures of cisplatin, carboplatin, tetraplatin and iproplatin: in each series, one ammine ligand of the parent compound carries various aliphatic or alicyclic substituents. L1210/cis retained sensitivity to compounds based on cisplatin (amine = isobutylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, ethyl 3-aminobutyrate, cyclohexylamine), carboplatin (amine = isobutylamine, cyclopentylamine, cyclohexylamine and the related complex ammine(benzylmalonato)cyclobutylamineplatinum(II)) and tetraplatin (amine = isopropylamine, tert-butylamine, cyclohexylamine). The L1210/tetra line was cross-resistant to all of these compounds (3.9- to 22.9-fold). However, both resistant variants retained sensitivities to all transdihydroxodichloroplatinum(IV) compounds. In the alicyclic series (amine = cyclobutylamine, cyclopentylamine, cyclohexylamine and cycloheptylamine) potency increased on ascending the series, the cyclohexyl and cycloheptyl derivatives being tenfold more cytotoxic than iproplatin and its parent diammine against all three lines. These compounds warrant further evaluation in alternative screening models to assess their potential for further development.