In silico evaluation and In vivo testing of hydrazide-hydrazones bearing 2H-chromene and coumarin scaffold for analgesic activity

In silico evaluation and In vivo testing of hydrazide-hydrazones bearing 2H-chromene and coumarin scaffold for analgesic activity

Poster

1-Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia
2-Department of Pharmacology and Toxicology, Medical Faculty, Medical University of Sofia
3-Department of Pharmacology, University of Sofia ‘‘St. Kliment Ohridski”
4-Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia

We recently discovered that some of newly synthesized hydrazide-hydrazone derivatives bearing 2H-chromene and coumarin scaffold possess anticonvulsant activity in the maximal electroshock (MES) test. Due to the similarity between the mechanism of neuropatic pain and epileptogenesis, our aim was to test the substances with demonstrated anticonvulsant activity also for analgesic activity. Methods. Male ICR mice (body weight 20-30g) were injected intraperitoneally with the tested substances in dosages equal of the ED50, as previously determined in the MES test. The hot plate test and the formalin paw tests were applied for assessment of analgesic activity. In silico evaluation was performed with PASS (Prediction of Activity Spectra for Substances) software with rodent acute toxicity prediction. Results. At the dose of 12.51 mg/kg the 2-furyl substituted derivative of the 2H-chromene demonstrated analgesic activity during the hot plate test by significantly increasing the latency time (p<0.05 vs controls). A similar effect was observed in the first phase of the formalin paw test. In silico results for this substance suggest a MAO inhibition activity and this could be a plausible explanation of the observed analgesic effect. Acute rodent toxicity prediction of this chemical was estimated as OECD class 5 (rat IP LD50=660.3 mg/kg). Conclusion. Sets of hydrazide-hydrazones having chromene or coumarin scaffolds were tested for analgesic activity. 2-Furyl substituted derivative of the 2H-chromene demonstrates analgesic activity by two tested methods and low toxicity. Further evaluations are needed for the elucidation of the mechanism of the observed analgesic and anticonvulsant effects of this substance.Acknowledgement. The study has been financially supported with Grant D-74/2017 of the Council of Medical Sciences, MU-Sofia