New 4-(2-furyl)-1,4-dihydropyridine-2-thiols as potential agents with anti-inflammatory activity

We synthesized new 1,4-dihydropyridine-2-thiols containing a 2-furyl substituent at position 4.

Based on the results of virtual bioscreening, seven samples with laboratory codes mar-014, mar-033, mar-035, mar-036, mar-037, mar-040, mar-075 were selected as the most promising compounds, taking into account the assumed biological targets of pharmacocorrection of the inflammatory process in preclinical studies.

The experiment was implemented in white male rats. Evaluation of the anti-inflammatory activity of the synthesized compounds was carried out on the model of acute "formalin edema", simulated by subplantar injection of formalin solution into the right hind limb . The substances were administered intragastrically, two hours before the induction of edema.

Animals of the control group received an equivalent amount of sodium chloride solution. Diclofenac sodium, indomethacin, meloxicam, and metamizole sodium intragastrically were used as comparison drugs .

The anti-inflammatory effect was assessed oncometrically, one and two days after the induction of inflammation, by changing the size of the limb.

The most pronounced anti-inflammatory activity at a dose of 5 mg / kg is possessed by: mar -040 33-fold superior to indomethacin, 26-fold to diclofenac sodium, 25-fold to meloxicam, and 30-fold to analgin; mar -037 was 17-23-fold superior to reference drugs; mаr -014 and mar -033 were 2.7-fold more efficient than the comparison drug.

Compounds mar-035 and mar-036 exhibited an anti-inflammatory activity similar to meloxicam, diclofenac and metamizol sodium.