Platinum-group metal half-sandwich complexes with C-glucopyranosyl 1,2,3-triazoles and isoxazoles as ligands: synthesis and evaluation as antineoplastic and antimicrobial agents.

IF 4.7 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Rahaf Akel, Alshimaa I Zaki, Éva Kerekes, István Kacsir, György Attila Kiss, Csongor Freytag, Evelin Szoták, Dóra Boros-Pál, Eszter Anna Janka, Gábor Kardos, Péter Bai, László Somsák, Sándor Kun, Adrienn Sipos, Éva Bokor
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Abstract

Half-sandwich complexes of platinum-group metals are a widely studied subgroup of organometallic compounds with promising anticancer and antimicrobial properties. Recently, we have published a set of polyhapto arene/arenyl Ru(II), Os(II), Ir(III) and Rh(III) complexes with hetaryl-substituted 1-N-glucopyranosyl-1,2,3-triazole and C-glycopyranosyl-1,3,4- and -1,2,4-oxadiazole-type N,N-bidentate ligands, several of which exhibited (sub)micromolar antineoplastic and bacteriostatic potencies. The structure-activity relationships of these series indicated that the nature of the azole ring and its way of connection to the pyranoid sugar unit played crucial roles in the biological activity of such complexes. In order to further study the influence of the five-membered heteroaromatic moiety, in this work we have synthesised new complexes with O-protected 4-C-(β-D-glucopyranosyl)-1-(pyridin-2-yl)-1,2,3-triazoles and 5-C-(β-D-glucopyranosyl)-3-(pyridin-2-yl)-isoxazoles as N,N-chelating ligands of η6-p-cym-Ru(II)/Os(II) and η5-Cp*-Ir(III)/Rh(III) complexes and have studied their cytostatic and antibacterial properties. All but the Rh(III)-derived complexes exerted cytostasis on a plethora of neoplasia cell models. The Ru(II)- and Os(II)-based complexes had the best IC50 values. The isoxazole-containing compounds outperformed the triazole-containing ones in terms of their cytostatic properties with submicromolar IC50 values. A subset of the complexes with Ru(II) and Ir(III) ions had bacteriostatic properties with low micromolar MIC values.

以c -葡萄糖吡喃基1,2,3-三唑和异恶唑为配体的铂族金属半夹心配合物:作为抗肿瘤和抗菌药物的合成和评价。
铂族金属半夹层配合物是一类被广泛研究的有机金属化合物,具有良好的抗癌和抗菌性能。最近,我们发表了一组聚半芳烃/芳烃Ru(II), Os(II), Ir(III)和Rh(III)配合物,这些配合物与己基取代的1-N-葡萄糖吡喃基-1,2,3-三唑和c -甘炔吡喃基-1,3,4-和-1,2,4-恶二唑型N,N双齿配体配合,其中一些具有(亚)微摩尔抗肿瘤和抑菌活性。这些系列的构效关系表明,唑环的性质及其与吡喃糖单元的连接方式对这些配合物的生物活性起着至关重要的作用。为了进一步研究五元杂芳部分的影响,我们合成了新的o保护的4-C-(β- d -葡萄糖吡喃基)-1-(吡啶-2-基)-1,2,3-三唑和5-C-(β- d -葡萄糖吡喃基)-3-(吡啶-2-基)-异恶唑配合物,作为η - 6-p-cym- ru (II)/Os(II)和η - 5- cp *- ir (III)/Rh(III)配合物的N,N螯合配体,并研究了它们的细胞抑制和抗菌性能。除了Rh(III)衍生的复合物外,所有复合物都对过多的肿瘤细胞模型施加细胞抑制作用。Ru(II)-和Os(II)基配合物的IC50值最好。含异恶唑的化合物在亚微摩尔IC50值方面优于含三唑的化合物。一类含有Ru(II)和Ir(III)离子的配合物具有低微摩尔MIC值的抑菌性能。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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