Synthesis and antitumor activities of alkyl-1,4-butanediamine Pt(II) complexes having seven-membered ring structure.

Abstract

Novel alkyl-1,4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and Lewis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1,1-dicarboxylate. 1,4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II) (five-membered ring) and 1,3-propanediamine Pt(II) (six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1,4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1,1-dimethyl-1,4-butanediamine Pt(II) complexes. In particular, 2,2-dimethyl-1,4-butanediamine and 2,3-dimethyl-1,4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1,1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values around 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1,4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.

Synthesis, DNA interaction and cytotoxicity studies of cis-{[1, 2-bis(aminomethyl)cyclohexane]dihalo}platinum(II) complexes

“…The synthesis of the diiodo platinum compounds for the other diamines was performed by using K 2 PtI 4 [11][12][13][14][15]. This compound was prepared in situ starting from K 2 PtCl 4 and a large excess of potassium iodide.…”

“…Thus, for the series 12-15, there are interesting differences in the circular dichroism behaviour between the compounds with a double bond (14,15) and the compounds with the aliphatic or aromatic ring (12,13). For the compounds with a substituent on the C-3 position, there is a wide variety of behaviours: (a) Among the methoxylated complexes, differences between the compounds with and without a double bond were observed, and (b) The compounds 16 and 17 having C@C double bond also showed differences in the ellipticity, indicating that the ligand configuration may affect the interaction of the molecule of complex with DNA at this level.…”

“…Abbreviations used for the reported 1 H NMR spectra are as follows: s = singlet, d = doublet, t = triplet, dd = doublet of doublets, dt = doublet of triplets, m = multiplet. 13 C NMR and DEPT experiments were recorded at 50 MHz, 75 MHz or 100 MHz and were referenced to the 77.0 ppm resonance of CDCl 3 . Mass spectra were run on a Fisons VG Quattro triple quadrupole analyser in the 1800-200 m/z range, fitted with a canon working at 10 kV.…”

A Kinetically Mechanistic Investigation of Oxidation of 1,4‐Butanediamine by Ag(III) Complex in Alkaline Medium

“…6 1,4-Butaneamine, expressed as R in the text, has disagreeable odor, which is a toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. It is a good ligand used to prepare Pt(II), Pt(IV) complex, 7 which have an anti-cancer activity.…”

Potential new antitumor agents from an innovative combination of camphorato, a ramification of traditional Chinese medicine, with a platinum moiety

“…This point of view leads to the design of antitumor drugs focusing mainly on the chirality of the carrier ligand. [32][33][34][35][36] The complexes with diamines of R or RR absolute configuration are slightly more active than the complexes with the corresponding diamines owning S, SS or RS configuration. 37 The study of four optical isomers of (mandelato)(trans-1,2-diaminocyclohexane)platinum(II) compounds indicated that the chiralities of both carrier ligands and leaving groups affect the antitumor activities of the complexes.…”