Department of Chemistry and Polymer Science, Stellenbosch University, 7600, Matieland, Western Cape, South Africa.
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
Chemistry. 2020 Jul 17;26(40):8676-8688. doi: 10.1002/chem.201904699. Epub 2020 May 26.
Resistance to chemotherapy is a current clinical problem, especially in the treatment of microbial infections and cancer. One strategy to overcome this is to make new derivatives of existing drugs by conjugation to organometallic fragments, either by an appropriate linker, or by direct coordination of the drug to a metal. We illustrate this with examples of conjugated organometallic metallocene sandwich and half-sandwich complexes, Ru and Os arene, and Rh and Ir cyclopentadienyl half-sandwich complexes. Ferrocene conjugates are particularly promising. The ferrocene-chloroquine conjugate ferroquine is in clinical trials for malaria treatment, and a ferrocene-tamoxifen derivative (a ferrocifen) seems likely to enter anticancer trails soon. Several other examples illustrate that organometallic conjugation can restore the activity of drugs to which resistance has developed.
化疗耐药性是当前的临床问题，特别是在治疗微生物感染和癌症方面。克服这一问题的一种策略是通过与金属有机片段的连接来制备现有药物的新衍生物，无论是通过适当的连接子，还是通过药物与金属的直接配位。我们用共轭金属茂夹心和半夹心配合物、Ru 和 Os 芳基以及 Rh 和 Ir 环戊二烯基半夹心配合物的例子来说明这一点。二茂铁衍生物特别有前途。二茂铁-氯喹偶联物 ferroquine 正在进行治疗疟疾的临床试验，而二茂铁-他莫昔芬衍生物（ferrocifen）似乎很快就会进入抗癌试验。其他几个例子表明，金属有机共轭可以恢复对耐药性发展的药物的活性。
