英國研究人員最新報告說，用兩種稀有金屬釕和鋨制成的化合物，可有效用于治療結腸癌和卵巢癌等癌癥。
釕,、鋨、鉑這類金屬元素的化學性質比較相近,，它們的原子可以與DNA（脫氧核糖核酸）分子結合,，能促使癌細胞凋亡。上世紀70年代,，含鉑的高效抗癌藥物“順鉑”誕生后,，人們就一直在尋找利用這類金屬元素研制新抗癌藥物的可能性。
英國沃里克大學和利茲大學研究人員在美國《醫(yī)學化學雜志》（Journal of Medicinal Chemistry）上報告說,，他們發(fā)現(xiàn)用釕和鋨制成的化合物，可以導致結腸癌和卵巢癌的癌細胞死亡,。而且,，那些已經對于“順鉑”產生抗藥性的癌細胞在遇到新化合物之后也會死亡。
研究人員說,，新研制出的化合物還有一大優(yōu)點,，就是通過特殊設計，其活性可以像開關那樣“打開”或“關閉”,。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Med. Chem., Article ASAP DOI: 10.1021/jm900731j
Amide Linkage Isomerism As an Activity Switch for Organometallic Osmium and Ruthenium Anticancer Complexes
Sabine H. van Rijt?, Andrew J. Hebden?, Thakshila Amaresekera?, Robert J. Deeth?, Guy J. Clarkson?, Simon Parsons§, Patrick C. McGowan*? and Peter J. Sadler*?
Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.
School of Chemistry, University of Leeds, Leeds LS2 9JT, U.K.
School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, U.K.
We show that the binding mode adopted by picolinamide derivatives in organometallic OsII and RuII half-sandwich complexes can lead to contrasting cancer cell cytotoxicity. N-Phenyl picolinamide derivatives (XY) in OsII (1, 3?5, 7, 9) and RuII (2, 6, 8, 10) complexes [(η6-arene)(Os/Ru)(XY)Cl]n+, where arene = p-cymene (1?8, 10) or biphenyl (9), can act as N,N- or N,O-donors. Electron-withdrawing substituents on the phenyl ring resulted in N,N-coordination and electron-donating substituents in N,O-coordination. Dynamic interconversion between N,O and N,N configurations can occur in solution and is time- and temperature- (irreversible) as well as pH-dependent (reversible). The neutral N,N-coordinated compounds (1?5 and 9) hydrolyzed rapidly (t1/2 ≤ min), exhibited significant (32?70%) and rapid binding to guanine, but no binding to adenine. The N,N-coordinated compounds 1, 3, 4, and 9 exhibited significant activity against colon, ovarian, and cisplatin-resistant ovarian human cancer cell lines (3 4 > 1 > 9). In contrast, N,O-coordinated complexes 7 and 8 hydrolyzed slowly, did not bind to guanine or adenine, and were nontoxic.
