Tumor acidity, ion trapping and chemotherapeutics

Ruthenium(II) Complexes of Thiosemicarbazones: The First Water‐Soluble Complex with pH‐Dependent Antiproliferative Activity

“…may therefore contribute to the reduced chemosensitivity of acidic tumours. [43][44][45] On the other hand, weakly acidic drugs such as chlorambucil are more cytotoxic when the extracellular pH is slightly acidic. [44,46] These observations are consistent with ion trapping, according to which weak electrolytes that are not transported actively concentrate in the compartment where their ionised fraction is larger.…”

“…[43][44][45] On the other hand, weakly acidic drugs such as chlorambucil are more cytotoxic when the extracellular pH is slightly acidic. [44,46] These observations are consistent with ion trapping, according to which weak electrolytes that are not transported actively concentrate in the compartment where their ionised fraction is larger. Ion trapping has also been discussed as a possible explanation for the pH-dependent cellular uptake and cytotoxicity of the metal complex cisplatin, the hydrolysis products of which are in a pH-dependent equilibrium.…”

Possible mechanisms of controlling the configuration, stability, and lipophilicity of [99mTcO]N3S and [ReO]N3S chelates

“…Reduction of Na[ 99m TcO 4 ] by SnCl 2 usually yields 99m TcO 31 ion, which can be stabilized and neutralized by tetradentate chelators such as L,L-ethylenedicysteine (where 99m Tc is coordinated by two nitrogen and two sulfur atoms, N 2 S 2 -type chelator), 1,2 mercaptoacetylglycylglycylglycine (N 3 S type), 3 hexamethyl propylene amine oxime (N 4 type), 4,5 and ethyl cysteinate dimer (N 2 S 2 ). 6,7 Those chelates exhibit a distorted square pyramidal geometry and theoretically exist syn and anti stereoisomers, depending on the orientation of the backbone substitutions with respect to the metal-oxo bond.…”

Acidic pH of Tumor Microenvironment Enhances Cytotoxicity of the Disulfiram/Cu²⁺ Complex to Breast and Colon Cancer Cells

“…A number of mechanisms have been postulated to be responsible for this effect, including direct impact of ion gradients on drug distribution, the pH-dependent activity of target enzymes and/or altered cell cycle kinetics [6,7,8]. Disulfiram (DSF), the dithiocarbamate drug capable of inhibiting alcohol and aldehyde dehydrogenases can also inhibit growth of cancer cells.…”