Reactions of the anticancer drug carboplatin ("Paraplatin") with a variety of sulfur-containing amino acids have been investigated by (1)H and (15)N NMR spectroscopy and by HPLC. Thiols react very slowly and sulfur-bridged species containing four-membered Pt(2)S(2) rings are the predominant products. In contrast, reactions with thioether ligands are much more rapid, and kinetics for the initial stages of the reaction with L-methionine have been determined (k = 2.7 x 10(-)(3) M(-)(1) s(-)(1)). Surprisingly, very stable ring-opened species are formed such as cis-[Pt(CBDCA-O)(NH(3))(2)(L-HMet-S)] which has a half-life for Met-S,N ring-closure of 28 h at 310 K. A study of the formation of the analogous product for N-acetyl-L-methionine and its subsequent ring closure is reported. Reactions such as these may play a role in the biological activity of carboplatin.
NMR investigations of the kinetics and thermodynamics of the competitive binding of L-methionine (Met), L-histidine (His), and 5'-monophosphates of guanosine (5'-GMP), adenosine (5'-AMP), thymidine (5'-TMP) and cytidine (5'-CMP) to [Pt(dien)CI]+ (dien = 1,5-diamino-3-azapentane) in aqueous solution show that 5'-GMP selectively displaces S-bound Met, a finding which has implications for DNA platination by anticancer drugs in vivo.
Interest in antimicrobial gold complexes originated from the work of Robert Koch at the end of 19th century, who demonstrated that potassium dicyanidoaurate(I), K[Au(CN)2], showed activity against Mycobacterium tuberculosis, a causative agent of tuberculosis. Subsequently, a large number of gold(I) and gold(III) complexes have been evaluated as possible antimicrobial agents against a broad spectrum of bacteria, fungi and parasites. The first part of the present review article summarizes the results achieved in the field of antibacterial and antifungal activity of gold(I) and gold(III) complexes. The represented gold(I) complexes have been divided into three distinct classes based on the type of coordinated ligand: (i) complexes with phosphine-type ligands, (ii) complexes with N-heterocyclic carbene ligands and (iii) various other gold(I) complexes, while the results related to the antibacterial and antifungal gold(III) complexes have been mainly focused on the organometallic-type of complexes. The second section of this article represents findings obtained from the evaluation of antimalarial activity of gold complexes against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum parasite. Antimalarial gold(I) and gold(III) complexes have been divided into the following classes, based on the nature of the coordinated ligand: (i) complexes with chloroquine and its derivatives, (ii) complexes with N-heterocyclic carbene ligands, (iii) complexes containing functionalised alkynes and (iv) thiosemicarbazonato ligands, as well as (v) other gold(I) and gold(III) complexes. In the last section of the review, gold(I) and gold(III) complexes have been reported to be potential agents against parasites that cause amoebiasis, leishmaniasis and trypanosomiasis. A systematic summary of these results could contribute to the future design of new gold(I) and gold(III) complexes as potential antimicrobial agents.
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