Anoxia,calcium and contracture as mediators of myocardial enzyme release

The effects of anoxia and calcium-free perfusion on enzyme release, were studied in perfused rat hearts, at 37°C. In oxygenated hearts, calcium-free medium caused detachment of cells at intercalated discs, but no cell separation or enzyme release. Sixty minutes of anoxia with calcium-free medium caused striking cell separations, contracture of sarcomeres and enzyme release. Anoxia, followed by calcium-free medium, produced a sudden, energy-independent enzyme release with contracture and cell separations. Contraction bands as well as cell separations, were present in anoxic hearts reoxygenated in the absence of calcium. It is proposed that calcium-free media causes loss of integrity of intercalated disc junctions and contraction, and anoxic contracture pulls cells apart at weakened cell junctions, mediating membrane damage and enzyme release.     

Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives

Background and the purpose of the study

There has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.

Methods

The title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.

Results

Although the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC₅₀ values = 7.56–25.04 μg/ml).

Conclusion

The results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.