Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo

Abstract

This study evaluated the antitumour activity of the mesoionic compound sydnone 1 (Syd-1) against Walker-256 carcinosarcoma. Tumour cells were subcutaneously inoculated in the hind limb in male Wistar rats. The animals were orally treated for 12 days with Syd-1 (75 mg/kg) or vehicle. At the end of treatment, considerable decreases in tumour volume and tumour weight were observed in treated animals. Samples of these tumours presented increases in apoptotic bodies and pro-apoptotic protein expression (Bax and p53), while the expression of the anti-apoptotic protein Bcl-2 was reduced. A decrease in reduced glutathione levels and an increase in glutathione peroxidase activity were observed in tumour after Syd-1 treatment. However, significant splenomegaly was evident in animals that received Syd-1, most likely attributable to the induction of haemolysis. This study demonstrated the antitumour activity of Syd-1 against Walker-256 carcinosarcoma. Its mechanism of action is linked to the activation of apoptotic pathways that lead to tumour cell death.

The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

“…It is one of the most widely used transplantable tumors in experimental research (Justice, 1985; Brigatte et al, 2007; Fan et al, 2016; Gambeta et al, 2016; Gao et al, 2016; Sroka et al, 2016; Wu M. et al, 2016). Indeed, these cells are one of the most preferred cell lines because of the ease with which they can be standardized, maintained and propagated in vitro , as well as their extensive use in vivo since 1937 (Michaelson and Orcutt, 1957; Brigatte et al, 2016; Galuppo et al, 2016; Pigatto et al, 2016; Trashkov et al, 2016; Yalovenko et al, 2016). …”

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…Therefore, they attributed sydnone activity to the activation of apoptosis pathways by decreasing the expression of anti-apoptotic enzyme Bcl-2 and increasing both apoptotic bodies and proapoptotic proteins (Bax and p53). However, splenomegaly was observed in the treated animals, and it was linked to sydnoneinduced extravascular hemolysis [66].…”

Evaluation of Sydnone‐Based Analogues of Combretastatin A‐4 Phosphate (CA4P) as Vascular Disrupting Agents for Use in Cancer Therapy

“…[40,41] As shown in Figure 9, CA4P treated tumoursw ere significantly more necrotic than the untreated tumours, However,t reatment with 23 did not have an effect on tumour necrosis. Such al ack of response to 23 indicated that the compound mayn ot have reached the tumourb lood vessels and was either metabolised before it could act or it was rapidly excreted.O nly limited examples of mesoionic compounds have been tested in vivo [42,43] and their unusual structure makesi td ifficult to predict their pharmacokinetic profile and stability in the body.N onetheless,t his class of heterocycle has been ap opulart arget in medicinal chemistry over several years,a nd the establishmento fav iable administration route is therefore an important issue to address in the field. Further advancesi nt his area are the subjecto fa ctive investigation.…”