Tunable and improved antiproliferative activity of Pt (II)‐based organometallics bearing alkynyls and 1,2,3‐triazole moieties

Abstract

Synthesis and characterization of a set of four Pt (II)‐based organometallic compounds (7–10) are being described. These molecules are unique since each of these contain three biologically active structural motifs, in the form of a pyrazine ring that connects a Pt‐alkynyl and a triazole ring. These organoplatinum molecules have been characterized using multinuclear nuclear magnetic resonance (NMR) (1H, 13C{1H}, and 31P{1H}), Fourier transform infrared spectroscopy (FT–IR), and mass spectrometry (MS). Additionally, the antiproliferative activities of 7–10 were probed against human triple‐negative breast cancer cells (MDA‐MB‐231) and normal human dermal fibroblast cells (HDF).

Self‐assembled neutral and ionic [2 + 2] metallomacrocycles using a new flexible ditopic Pt(II)‐based organometallic tecton bearing a pyrimidine motif: Facile syntheses and enhanced anticancer potency

“…In the recent past, we have reported few biologically active and neutral organometallic molecules and macrocycles of Pt II that also contained pyrazine unit. [ 33,35,86 ] Antiproliferative activity of these pyrazine‐based Pt II organometallics were comparable with that of cisplatin. It was our curiosity to find out if replacement of the pyrazine unit with pyrimidine (to obtain a new isomeric molecule in the form of 3 ) resulted in any significant changes in the biological activities of 3 .…”

“…[13,[26][27][28][29][30][31] In addition to anticancer activities reported for various metal-based organometallic compounds, the ability of discrete supramolecular entities such as "metallacycles" and "metallacages" to inhibit growth of cancer cells has been also investigated in recent years. [10,[32][33][34][35][36][37][38][39] As a proof of concept, cytotoxicity of these species was determined against different cancer cells, and their anticancer potency was compared with the "gold standard" cisplatin. [40] Although the results are quite promising, research in the domain of development of organometallic compounds with anticancer potencies is its infancy, and there is immense scope to develop newer molecules for this application.…”

Flexible and rigid ionic organoplatinum complexes and their antiproliferative activities

“…Cisplatin is considered as a "gold standard" to compare the cytotoxicity of newly developed organometallic species with potential as anticancer compounds. 1,2 Cisplatin and its derivatives (carboplatin, oxaliplatin, and others) are approved by the Food and Drug Administration (FDA) and are currently used for effective treatment of various types of cancers. 3,4 However, reduced efficiency and increased toxicity upon prolonged use of these platinum-based drugs are among the major limitations in their use.…”

“…Structural diversity is incorporated by using spacers of different lengths and bond directionalities. We have not just restricted to pyrazine 2,19,33 but have also incorporated other nitrogen-rich heterocyclic aromatic moieties in the structural framework of the organometallic species. 31,34 Specifically, the core of 1 and 2 are flexible while that of 3, 4, and 5 are rigid.…”

“…Since it was our interest to study the difference in biological activity based on differences in the shape and structure of the molecules, the cytotoxicity of the five organometallic complexes were studied against HeLa cells. It was our interest to investigate the dose-dependent cytotoxicity of these positively charged organometallic complexes (1)(2)(3)(4)(5). The relevant data were obtained by using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, which is a colorimetric assay to obtain cellular metabolic activity-oriented information.…”