The possibility of using cell test-systems for screening for anti-inflammatory activity of novel 5(S)-menthyloxy derivatives of 2(5H)-furanone

Aim. Study of the possibility of using cell experimental models (erythrocytes hemolysis and platelet aggregation) for screening for anti-inflammatory activity of novel synthesized 5(S)-menthyloxy derivatives of 2(5Н)-furanone (compounds R1-R6). Methods. Evaluation of membrane-stabilizing activity of the test compounds was performed by means of models of erythrocyte hemolysis induced by hypotonic environment (osmotic hemolysis) and free radicals. Antiplatelet effect of the compounds was studied by inducing platelet aggregation by 1 mM arachidonic acid. Study of anti-inflammatory activity of novel potential anti-inflammatory molecules was performed with the use of the model of carrageenan-induced paw edema in mice. Results. Compounds R1, R2, R3, and R4 increase the degree of osmotic hemolysis. Compounds R5, R6 decrease the intensity of hemolysis at different concentrations. Compounds R1, R2, R4 and R6 promote free-radical erythrocyte membrane damage at all tested concentrations. Compound R3 protects erythrocytes at low concentrations and promotes erythrocyte damage with increasing concentration. Compound R5 protects erythrocytes at concentrations 3×10-9 и 3×10-5 М. Compounds R1, R2, R4 enhance platelet aggregation at different concentrations. Compound R3 inhibits platelet aggregation at concentration 10-6 М, and at concentrations 10-8 and 10-5 М it induces platelet aggregation. Compound R5 does not affect platelet aggregation. Compound R6 inhibits platelet aggregation at all tested concentrations. On the basis of the results obtained from in vitro test systems compound R6 was selected for further studies of anti-inflammatory activity as it demonstrated maximum effect based on two out of three evaluation criteria. Compound R6 posseses anti-inflammatory activity in the model of inflammation. Conclusion. The novel derivative of 2(5Н)-furanone bearing l-menthol moiety (compound R6) protects erythrocyte membrane from damaging action of hypotonic environment, inhibits platelet aggregation and demonstrates anti-inflammatory activity; cell experimental models can be used for the first phase of screening of novel chemical compounds for anti-inflammatory activity.

Tenuazonic acid: a promising antitubercular principle from Alternaria alternate

Bioactivity guided isolation of dichloromethane extract of <em>Alternaria alternata</em> identified tenuazonic acid (1) as potentially active against <em>Mycobacterium tuberculosis</em> H37Rv, MIC at 250 μg/mL concentration. This active metabolite 1, was also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that this fungal metabolite showing antitubercular activity exhibited concentration dependent toxicity to human erythrocytes.