Cytotoxic Activity of Metal Complexes of Biogenic Polyamines:  Polynuclear Platinum(II) Chelates

Abstract

Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied were designed to differ in geometrical parameters such as the nature of the ligand and the number and chemical environment of the metal centers. Distinct effects were found for different cell lines and different structural characteristics of the complexes; chelates II, III, and IV displayed specificity toward the HeLa and HSC-3 epithelial-type cells, while V, VI, and VII were clearly more effective against the THP-1, MOLT-3, and CCRF-CEM leukemia cell lines. The toxicity of these Pt(II) complexes on noncancer cells was, in all cases, found to be reversed upon drug removal.

Effect of the Metal Center on the Antitumor Activity of the Analogous Dinuclear Spermine Chelates (PdCl2)2(Spermine) and (PtCl2)2(Spermine)

“…In this manuscript, we describe the cytotoxic effects towards a human cancer cell line (HSC-3) of the dinuclear Pd(II) spermine (sp) chelate (PdCl 2 ) 2 (sp) (Fig. (1)) and compare it to that previously reported by the authors for the analogous Pt(II) chelate [12]. The results obtained confirm and extend those previously obtained with another polynuclear cis-dichloro(chelating diamine) system [13], i.e., an increase in cytotoxic activity upon substitution of Pt(II) with Pd(II).…”

A molecular view of cisplatin's mode of action: interplay with DNA bases and acquired resistance

“…The detailed knowledge of the molecular basis of the cDDP-guanine/adenine and cDDPglutathione interplay gathered in this work will pave the way for future studies on other platinum and palladium-based agents previously characterized by the authors and assessed as to their cytotoxicity towards several human cancer cell lines. [29][30][31][32][33][34][35][36][37] This will provide valuable clues for the rational design of novel cisplatin-like drugs, displaying a higher efficiency, lower toxicity, decreased acquired resistance and possible oral administration. …”

Spectroscopic and Theoretical Studies on Solid 1,2‐Ethylenediamine Dihydrochloride Salt

“…[6,15,17,18] In addition, it was verified that linkage of some of these molecules to previously tested anticancer drugs leads to a higher cytotoxic effect and, in some cases, even to an enhancement of the efficacy of the long-used first-generation drug cisplatin [cis-diamine dichloroplatinum(II)]. [19][20][21][22][23][24][25][26][27] Recently, it was also demonstrated that polyamines may exert insulinlike activity by interacting with receptors on fat-cell membranes. [28] Despite the vital role of polyamines in living cells, little is known about their structure at a molecular level.…”