Discovery of new pyridine 3-carboxylic acid-based pharmacophores as dual anti-inflammatory and anti-hyperglycemic agents

Novel nicotinic acid derivatives were synthesized as potent anti-diabetic agents. The developed inhibitors were investigated for their pharmacological in vitro screening, such as anti-diabetic, anti-inflammation, and in silico analysis. It has good interactions with α-amylase protein, with a range of -7.18 to -5.55 kcal/mol. The inhibitors were synthesized by employing the Steglich-type reaction to couple alcohol and amine derivatives. These molecules were characterized using NMR, FT-IR, and Mass spectrometry techniques. Anti-hyperglycemic activity has been screened using α-amylase protein, and the half-maximal inhibition efficiency (IC₅₀) value was evaluated, ranging from 1.324 ± 0.17 to 1.516 ± 0.14 µg. The positive control (acarbose) range is 1.273 ± 0.12 µg. Induced human RBC hemolysis assay was utilized for anti-inflammatory activity, and the cumulative observation results were compared with the reference drug (ketorolac- IC₅₀ = 11.79 ± 0.17 µM), with IC₅₀ values between 14.06 ± 0.15 to 85.56 ± 0.25 µM. Moreover, the antioxidant ability of synthesized inhibitor compounds was evaluated by radical scavenging methods. The efficacy of inhibitors 2b and 2 h (IC₅₀ = 15.63 ± 0.13 µM and 12.88 ± 0.19 µM (DPPH), IC₅₀ = 19.89 ± 0.25 µM and 16.35 ± 0.25 µM (ABTS)) exhibited good results against DPPH and ABTS radicals with ascorbic acid(standard) (DPPH: IC₅₀ = 11.81 ± 0.04 µM and ABTS: 11.90 ± 0.01 µM). The synthesized derivatives show promising results of anti-inflammatory and anti-hyperglycemic properties. This provides a path to developing the new therapeutic agents for inflammation.