英国研究人员最新报告说，用两种稀有金属钌和锇制成的化合物，可有效用于治疗结肠癌和卵巢癌等癌症。
钌、锇、铂这类金属元素的化学性质比较相近，它们的原子可以与DNA（脱氧核糖核酸）分子结合，能促使癌细胞凋亡。上世纪70年代，含铂的高效抗癌药物“顺铂”诞生后，人们就一直在寻找利用这类金属元素研制新抗癌药物的可能性。
英国沃里克大学和利兹大学研究人员在美国《医学化学杂志》（Journal of Medicinal Chemistry）上报告说，他们发现用钌和锇制成的化合物，可以导致结肠癌和卵巢癌的癌细胞死亡。而且，那些已经对于“顺铂”产生抗药性的癌细胞在遇到新化合物之后也会死亡。
研究人员说，新研制出的化合物还有一大优点，就是通过特殊设计，其活性可以像开关那样“打开”或“关闭”。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
