Design, Synthesis, and Biological Activity of a Novel Non-Cisplatin-type Platinum−Acridine Pharmacophore

Abstract

Platinum-acridine conjugates were prepared from [PtCl2(ethane-1,2-diamine)] and the novel acridinylthioureas MeHNC(S)NMeAcr (6) and MeHNC(S)NMe(CH2CH2)NHAcr (15) by replacing one chloro leaving group in the cisplatin analogue with thiourea sulfur. In HL-60 leukemia cells, IC(50) values for 7 (Pt-tethered 6) and 16 (Pt-tethered 15) were 75 and 0.13 microM, respectively. In the ovarian cell lines 2008 and C13, 16 was active at micromolar concentrations and showed only partial cross-resistance with clinical cisplatin. Possible structure-activity relationships are discussed.

Human Serum Albumin-Delivered [Au(PEt3)]+ Is a Potent Inhibitor of T Cell Proliferation

“…The rationale behind testing the current set of thioureas was to establish the structural requirements for L as a carrier group. While ACRAMTU-based ligands alone proved to be significantly less cytotoxic than their Pt and Au complexes in all solid and hematological tumor models studied, 11,16 one goal of the screen was to establish whether the intercalator can be replaced with non-DNA binding, less genotoxic moieties. For comparison, the nine chlorogold(I) precursors, [AuClP#] (with L10 = chloride), were also included in the screen.…”

Synthesis of Dimeric Trifluoromethoxyacridine‐derived Pathogen‐inactivating Nucleic Acid Intercalators

“…From preliminary modelling studies we deduced that the presence of a 2-trifluormethoxy moiety in the acridine ring should result in an improved interaction between the intercalator and the nucleic acids. [11,12] gave the acridinyl carbamates 9Ϫ15, respectively. These acridinyl carbamates were deprotected using aqueous hydrochloric acid to afford the corresponding bishydrochlorides 16Ϫ22.…”

cis-Diammine[3-(3-chloro-7-methoxy-9,10-dihydroacridin-9-ylideneamino)propan-1-amine-κ2N,N′]platinum(II) dinitrate

“…Unfortunately, due to the widespread use of platinum drugs, patients began to develop drug resistance (Shen et al, 2012). Non-classical platinum drugs, for example, platinum-intercalator conjugates are thought to be an alternative solution to overcome cisplatin resistance (Johnstone et al, 2014;Baruah et al, 2004;Martins et al, 2001). We attempted to synthesize a 9-aminoacridine derivative linked with monofunctional platinum via a three-carbon alkyl chain.…”