Anticancer and Antimicrobial Metallopharmaceutical Agents Based on Palladium, Gold, and Silver N-Heterocyclic Carbene Complexes

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• 作者：Sriparna Ray ; Renu Mohan ; Jay K. Singh ; Manoja K. Samantaray ; Mobin M. Shaikh ; Dulal Panda ; Prasenjit Ghosh
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：December 5, 2007
• 年：2007
• 卷：129
• 期：48
• 页码：15042 - 15053
• 全文大小：583K
• 年卷期：v.129,no.48(December 5, 2007)
• ISSN：1520-5126

文摘

Complete synthetic, structural, and biomedical studies of two Pd complexes as well as Au andAg complexes of 1-benzyl-3-tert-butylimidazol-2-ylidene are reported. Specifically, trans-[1-benzyl-3-tert-butylimidazol-2-ylidene]Pd(pyridine)Cl₂ (1a) was synthesized from the reaction of 1-benzyl-3-tert-butylimidazolium chloride (1) with PdCl₂ in the presence of K₂CO₃ as a base. The other palladium complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]₂PdCl₂ (1b), and a gold complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AuCl(1c), were synthesized by following a transmetallation route from the silver complex, [1-benzyl-3-tert-butylimidazol-2-ylidene]AgCl (1d), by treatment with (COD)PdCl₂ and (SMe₂)AuCl, respectively. The silvercomplex 1d in turn was synthesized by the reaction of 1 with Ag₂O. The molecular structures of 1a-dhave been determined by X-ray diffraction studies. Biomedical studies revealed that, while the palladiumcomplexes 1a and 1b displayed potent anticancer activity, the gold (1c) and silver (1d) complexes exhibitedsignificant antimicrobial properties. Specifically, 1b showed strong antiproliferative activity against threetypes of human tumor cells, namely, cervical cancer (HeLa), breast cancer (MCF-7), and colonadenocarcinoma (HCT 116), in culture. The antiproliferative activity of 1b was found to be considerablystronger than that of cisplatin. The 1b complex inhibited tumor cell proliferation by arresting the cell cycleprogression at the G2 phase, preventing the mitotic entry of the cell. We present evidence suggesting thatthe treated cells underwent programmed cell death through a p53-dependent pathway. Though both thegold (1c) and silver (1d) complexes showed antimicrobial activity toward Bacillus subtilis, 1c was found tobe ca. 2 times more potent than 1d.