Synthesis, Characterization, and Interaction with Biomolecules of Platinum(II) Complexes with Shikimic Acid-Based Ligands

Abstract

Starting from the active ingredient shikimic acid (SA) of traditional Chinese medicine and NH2(CH2)nOH, (n = 2–6), we have synthesized a series of new water-soluble Pt(II) complexes PtLa–eCl2, where La–e are chelating diamine ligands with carbon chain covalently attached to SA (La–e = SA-NH(CH2)nNHCH2CH2NH2; La, n = 2; Lb, n = 3; Lc, n = 4; Ld, n = 5; Le, n = 6). The results of the elemental analysis, LC-MS, capillary electrophoresis, and 1H, 13C NMR indicated that there was only one product (isomer) formed under the present experimental conditions, in which the coordinate mode of PtLa–eCl2 was two-amine bidentate. Their in vitro cytotoxic activities were evaluated by MTT method, where these compounds only exhibited low cytotoxicity towards BEL7404, which should correlate their low lipophilicity. The interactions of the five Pt(II) complexes with DNA were investigated by agarose gel electrophoresis, which suggests that the Pt(II) complexes could induce DNA alteration. We also studied the interactions of the Pt(II) complexes with 5′-GMP with ESI-MS and 1H NMR and found that PtLbCl2, PtLcCl2, and PtLdCl2 could react with 5′-GMP to form mono-GMP and bis-GMP adducts. Furthermore, the cell-cycle analysis revealed that PtLbCl2, PtLcCl2 cause cell G2-phase arrest after incubation for 72 h. Overall, these water-soluble Pt(II) complexes interact with DNA mainly through covalent binding, which blocks the DNA synthesis and replication and thus induces cytotoxicity that weakens as the length of carbon chain increases.

Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex

“…In detail, the platination of the diamino ethane moiety in the complex 6 was confirmed by the downfield shift of the 13 C resonances of CH 2 NH 2 (Δδ ≈ 5 ppm) and CH 2 NH (Δδ ≈ 3 ppm each) compared with the same signals displayed by the diamine 14 . Conversely, the platination of C6NH, N1 and N3 nitrogen atoms could be excluded, as no significative differences between the chemical shift of carbons belonging to the purine rings of the two compounds were observed [ 47 ]. In the HRESI-MS(+) spectrum of complex 6 , the base peak corresponded to the protonated bis-chlorinated species; in addition, traces of the fragment ion [M − Cl] + ( m/z = 596.1347) were also detected.…”

Production and Synthetic Modifications of Shikimic Acid

“… , Platinum­(II) complexes with shikimic acid based ligands have been prepared by reaction of amide derivatives containing a diamine moiety with K 2 PtCl 4 (Scheme ), and have been shown to bound covalently to DNA, blocking the DNA synthesis and replication. The exact structure of the five water-soluble complexes of different alkyl chain lengths was not elucidated but purposed to have the ligands coordinated in a bidentate manner through the amine groups …”

Draft Genome Sequence of Pseudomonas chlororaphis ATCC 9446, a Nonpathogenic Bacterium with Bioremediation and Industrial Potential

“…Assembly was performed with SPAdes version 3.9.0 and IDBA_UD version 1.1.1 parallel, and the contigs obtained were merged and optimized using METASSEMBLER version 1.5 (12–14). Contigs were reordered using MAUVE version snapshot_2015_02_13 using the genome of P. chlororaphis 189 as a reference (15).…”

“…The genome of strain ATCC 9446v was sequenced at the Sequencing and Polymorphism Identification Unit of the Instituto Nacional de Medicina Genómica in a NextSeq 500 Illumina sequencer with a 2 × 150 paired-end indexed configuration, achieving a genome coverage of 120-fold. Assembly was performed with SPAdes version 3.9.0 and IDBA_UD version 1.1.1 parallel, and the contigs obtained were merged and optimized using METASSEMBLER version 1.5 ( 12 – 14 ). Contigs were reordered using MAUVE version snapshot_2015_02_13 using the genome of P. chlororaphis 189 as a reference ( 15 ).…”