ABSTRACT
Metallodrugs (organometallic complexes) bearing at least one metal-carbon bond - represent original and powerful tools for diverse therapeutic applications based on the development of "bioorganometallic chemistry". To date, various metallodrugs were described with very interesting biological activities as antimalarials, antibacterials, neuroprotectors, against arthritis, for chemotherapy etc. Anticancer Pt-based drugs are the main complexes used in the treatment of several cancers, but unfortunately these complexes show elicit and severe toxicities and resistance effects. The remarkably unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as diagnostics, gene therapy and drug delivery including in oncology. Recent studies have shown that well designed dendritic carriers overcome such as poor solubility, permeability, biocompatibility, bioavailability and toxicity of the native drug. This review reports on the recent advances for the use of metallodrugs and dendritic based carriers (drug-dendrimer conjugates and drug encapsulation) in oncology. Advantages, limitations and opportunities in oncology of such materials are discussed and compared.
Subject(s)
Coordination Complexes/chemistry , Dendrimers/chemistry , Drug Delivery Systems/methods , Metals/chemistry , Nanomedicine/methods , Neoplasms/drug therapy , Animals , Coordination Complexes/administration & dosage , Coordination Complexes/pharmacokinetics , Dendrimers/administration & dosage , Dendrimers/pharmacokinetics , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Humans , Metals/administration & dosage , Metals/pharmacokinetics , Neoplasms/metabolismABSTRACT
The azazirconacyclopentene-substituted phosphines 3 and 4 have been found to activate the C-H bonds of acetylenic systems, such as methylpropiolate, diphenylphosphinoacetylene and phenylacetylene, or of methylene compounds, such as malonitrile and diethylmalonate, to give complexes 5a-c, 6a and 6b. C-H bond activation also takes place with vinylacetate. Similar reactions with amines, alcohols, enolisable ketones, phenols, phosphonates, thiols and a second-generation SH-terminated dendrimer lead through X-H bond activation (X = N, O, P, S) to new complexes 8a-c, 9, 12 a,b, 13, 14a-c, 15, 16a and 16b. The azazirconacyclopentene-substituted amine 20 reacts to form analogous complexes. Zr-X bonds of these complexes (X = C, N, O, S) can be cleaved with diphenylchlorophosphine to give P-X phosphorus derivatives in high yield.
ABSTRACT
Polycyclic zwitterionic complexes that incorporate one or two phosphonium unit(s) as cationic center(s) and zirconocene-ate moiety(ies) as the anionic counterpart(s) can be easily prepared by either [1+3] or [1+3] and [2+3] cycloadditions which involve bi- or tricyclic alpha-zirconated phosphanes 3 or 4 and various azides. Some of these species exhibit unprecedented phosphazide chelation with bonding between the zirconium and a nitrogen atom in the alpha position relative to phosphorus. When heated, the phosphazide complexes lose dinitrogen to form stable polycyclic zwitterionic phosphonium mono- or dinuclear complexes. The solid-state structure of the two zwitterionic complexes 5 and 8 was determined by X-ray crystallography.
