Chellan Prinessa, Avery Vicky M, Duffy Sandra, Triccas James A, Nagalingam Gayathri, Tam Christina, Cheng Luisa W, Liu Jenny, Land Kirkwood M, Clarkson Guy J, Romero-Canelón Isolda, Sadler Peter J
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
Current address: Stellenbosch University, Matieland, Western Cape, South Africa.
Chemistry. 2018 Jul 17;24(40):10078-10090. doi: 10.1002/chem.201801090. Epub 2018 Jun 13.
Fourteen novel arene Ru , and cyclopentadienyl (Cp ) Rh and Ir complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by X-ray crystallography. The rhodium and iridium complexes exhibited potent antiplasmodial activity with IC values of 0.10-2.0 μm in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes) but were only moderately active towards Trichomonas vaginalis. They were active in both the asexual blood stage and the sexual late stage gametocyte assays, whereas the clinical parent drug, sulfadoxine, was inactive. Five complexes were moderately active against Mycobacterium tuberculosis (IC <6.3 μm), while sulfadoxine showed no antitubercular activity. An increase in the size of both the Cp ligand and the aromatic imino substituent increased hydrophobicity, which resulted in an increase in antiplasmodial activity.
已合成并表征了14种新型的包含与抗疟药物磺胺多辛官能化的N,N'-螯合吡啶基亚氨基或喹啉基亚氨基配体的芳烃钌、环戊二烯基（Cp）铑和铱配合物，其中三种通过X射线晶体学表征。铑和铱配合物在所有三种恶性疟原虫检测（3D7氯喹敏感株、Dd2氯喹耐药株和NF54有性后期配子体）中，或其中一种检测中表现出强效抗疟活性，IC值为0.10 - 2.0μm，但对阴道毛滴虫仅具有中等活性。它们在无性血液阶段和有性后期配子体检测中均有活性，而临床母体药物磺胺多辛无活性。五种配合物对结核分枝杆菌具有中等活性（IC<6.3μm），而磺胺多辛无抗结核活性。Cp配体和芳香基亚氨基取代基尺寸的增加会增加疏水性，从而导致抗疟活性增强。
