Mutagenicity of substituted (o-phenylenediamine)platinum dichloride in the Ames test. A quantitative structure-activity analysis

Abstract

A set of 13 substituted (o-phenylenediamine)platinum dichlorides has been studied in the Ames test using Salmonella typhimurium (TA-92). These cis-platinum compounds are mutagenic without activation by microsomes. The following correlation equation shows that the most important determinant of mutagenicity by substituents (X) is electron withdrawal via through resonance: log 1/C = 2.23 sigma sigma minus + 5.78. C in this expression is the molar concentration of compound producing 30 mutations/10(8) bacteria initially delivered above background mutation, and sigma minus is the Hammett constant obtained from substituted anilines.

Linear free energy relationship for 4-substituted (o-phenylenediamine)platinum(II) dichloride derivatives using quantum mechanical descriptors

“…In the present work, the hydrolysis processes for a series of 4-substituted dichloro-1,2-(phenylenediamine)platinum(II) compounds (o-phdPt), also known as dichloro(benzene-1,2-diamine)platinum(II) were investigated using quantum mechanical methods. This kind of aromatic diamine compounds was first considered by Connors and coworkers [30] and afterwards by Hansch and collaborators [31] who proposed a QSAR model correlating mutagenicity in the Ames test to the Hammett electronic parameters for a series of 4-and 4,5-substituted dichloro-1,2-(phenylenediamine)platinum(II). Kö ckerbauer and Bednarski [32] reported in 1996 a quite interesting paper dealing with the chemical stability of this class of molecules.…”

Synthesis and characterization of platinum(II) complexes from trifluoromethyl phenylenediamine, picoline and N-benzyl ethylenediamine derivatives

“…Compound 11 also showed a signal at δ 3.7 attribuited to the OCH 3 group. In the 13 C NMR, signals between δ 113.9-166.6 corresponding to the aromatic carbons were observed. For complex 11, one signal at δ 52.2 showed the presence of the methoxy group.…”

“…In the 13 C NMR spectra, signals at the δ 35 -50 region corresponding to the methylenic carbons and signals in the δ 115 to 160 region, due to the aromatic carbons, were observed. For compound 8, the signals corresponding to OCH 3 and C=O were observed at δ 52.1 and 166.2, respectively.…”

“…[11][12][13][14] This compound was screened in vitro against seven human cancer cell lines, MCF7 and EVSAT (mammary cancers), WiDr (colon cancer), IGROV (ovarian cancer), M19 (melanoma), MEL A498 (renal cancer) and H226 (lung cancer). The ID 50 values (in ng mL -1 ) obtained are presented in Table 1 together with those of clinically used drugs, doxorubicin (DOX), cisplatin (CPT), 5-fluorouracil (5-FU), methotrexate (MTX), etoposide (ETO) and taxol (TAX) for comparison.…”

“…For example, dichloro(o-phenylenediamine)platinum(II) complex ( Figure 1, a) was among the first cisplatin analogs found to possess antitumour activity. [11][12][13][14] Thus, Connors et al 11 have prepared different platinum(II) complexes which contains aromatic amines, such as 1,2-phenylenediamine and its derivatives, having different groups in the 4 position, such as chloro, methoxy, nitro and methyl. Later, Meischen et al 15 reported the antineoplastic activity 1267 Synthesis and Characterization of Platinum(II) Vol.…”