Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid

Abstract

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5–6 and 8a–8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

“…Compound 76 was one of the most potent anti-inflammatory agents, with IC 50 of 1.42±0.1 µg/mL. 214 The antagonizing hormone glucocorticoid stimulates hepatic glucose synthesis while inhibiting insulinassisted glucose absorption in skeletal muscles and adipose tissue. 215 Glucocorticoidal stimulation, which is coordinated by 11β-HSD2 and 11β-HSD1 enzymes, is often used to measure glucocorticoid target-tissue activity.…”

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

“…Yaqoob et al. 65 synthesised novel scaffolds containing isonicotinoyl motif derivatives and screened for their in vitro anti-inflammatory activity. Results showed that compound 50 ( Figure 5 ) exhibited an exceptional IC 50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL) 65 .…”

Pyridine derivatives as preferable scaffolds for the process of discovering new drugs

“…These medications are used to treat muscular and articular inflammatory diseases such osteoarthritis and rheumatoid arthritis. Yaqoob et al [17] created a class of strong anti-inflammatory drugs employing derivatives of Isonicotinic acid, such as pyridine. Figure 17 demonstrates the extremely high ROS-inhibitory activity of structures 77 and 79.…”

“…Figure 17 demonstrates the extremely high ROS-inhibitory activity of structures 77 and 79. Compound 77 was determined to be the most effective with an IC50 of 1.4 g/ML [17] . In 2019, Kandasamy et al [18] reported that they have developed a chemical that suppresses inflammation by blocking nitric oxide (NO) production at a concentration of 26 micromolar (M).…”