Anticancer activity of a cis-dichloridoplatinum(ii) complex of a chelating nitrogen mustard: insight into unusual guanine binding mode and low deactivation by glutathione

Dalton Transactions : an International Journal of Inorganic Chemistry
Subhendu KarmakarArindam Mukherjee

Abstract

A pyridine ring containing a chelating nitrogen mustard ligand bis(2-chloroethyl)pyridylmethylamine hydrochloride (L2·HCl) was synthesized from bis(2-hydroxyethyl)pyridylmethylamine (L1) on reaction with thionyl chloride. Both the ligands upon reaction with cis-[PtCl2(DMSO)2] afforded square planar complexes cis-[PtCl2(L1)] (1) and cis-[PtCl2(L2)] (2) respectively. Both the complexes were characterized by NMR, IR, UV and elemental analysis. 2 crystallized in the P21/c space group. 2 shows greater solution stability than 1 in kinetic studies by 1H NMR. Both 1 and 2 bind the model nucleobase 9-ethylguanine (9-EtG) and form multiple mono-adducts. Existence of unusual N7,O6 chelated guanine bound 2 (2e) was traced. Binding studies of 2 with glutathione (GSH) show formation of a mono-adduct cis-[PtCl(L2)SG] (2c), which transformed within a day to give an aziridinium ion of L2 (2b) after loss of L2. In vitro cytotoxicity of ligands, complexes and the clinical anticancer drug cisplatin show that 2 is the most potent against MCF-7, A549 and MIA PaCa2 exhibiting IC50 values of 12.6 ± 0.8, 18.2 ± 1.8 and 4.2 ± 1.0 μM respectively. The in vitro cytotoxicity of 2 against MCF-7, A549 and MIA PaCa2 was also probed in hypoxia and in the prese...Continue Reading

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Citations

May 28, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Subhendu KarmakarArindam Mukherjee
Jan 11, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Subhendu KarmakarArindam Mukherjee
Feb 6, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Moumita MajiArindam Mukherjee
Apr 22, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Yoojin SongYoung Ho Seo
Dec 29, 2020·Journal of Inorganic Biochemistry·Riccardo BondiSimona Samaritani
Jan 29, 2021·Dalton Transactions : an International Journal of Inorganic Chemistry·Mohammad UsmanSartaj Tabassum
Jan 9, 2020·Journal of Inorganic Biochemistry·Subhendu KarmakarArindam Mukherjee
Jan 7, 2021·Chemistry : a European Journal·Srividya SwaminathanRamasamy Karvembu
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Walaa AlharbiAli Alsalme
Oct 31, 2018·Inorganic Chemistry·Md Kausar RazaAkhil R Chakravarty
Mar 5, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mariam AbotalebDietrich Büsselberg

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