Comparative study of the effects of 1,3,4-thiadiazolium mesoionic derivatives on energy-linked functions of rat liver mitochondria.

The main goal of this work was to investigate the relationship between the effects of three new 1,3,4-thiadiazolium mesoionic derivatives on mitochondrial bioenergetics and their previously described chemical structure and antimelanoma activity. The 4-phenyl-5-(2'-Y, 4'-X or 4'-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chlorides differed from each other only in the cinnamoyl ring substituent: MI-J, X=OH; MI-F, X=F; MI-2,4diF X=Y=F. The state 3 respiratory rate was strongly decreased by all derivatives, reaching total inhibition of MI-4F and MI-2,4diF (130nmolmg(-1) protein), when glutamate plus malate were used as substrate.

The inhibition of lipoperoxidation by mesoionic compound MI-D: a relationship with its uncoupling effect and scavenging activity.

Important biological activities have been described for mesoionic compounds. We previously reported that MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride) inhibited the respiratory chain, collapsed the transmembrane potential, and stimulated ATPase activity in intact rat liver mitochondria. It is known that drugs that affect mitochondrial membrane potential may facilitate the induction of cell death by apoptosis.

Effect of a new 1,3,4-thiadiazolium mesoionic compound (MI-D) on B16-F10 murine melanoma.

The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compounds. In this study we evaluated the antitumour activity of 4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride (MI-D), a new mesoionic compound, against the mouse melanoma B16-F10 cell line.