Design, synthesis, anti-inflammatory evaluation and in silico molecular docking of novel furan-based derivatives with promising TNF-α inhibitory activity

Abstract

Abstract Inflammation is the first response and an alarming signal for onset of chronic disease. Most of the anti-inflammatory drugs available in market are reported to have undesirable gastrointestinal toxicities. Therefore, it is of urgently significance to develop anti-inflammatory drugs with low toxicity and good efficacy. Based on literature survey, we designed a targeted scaffold by condensing distinct structural features of furan and benzyl amides into one pharmacophore. The inspiration for drug design approach of targeted molecule was based on marketed drugs. A series of eighteen furan-based derivatives (1-18) were designed, synthesized for in-vitro and in-vivo anti-inflammatory activity. The characterization of synthesized compounds was elucidated by techniques like 1H-NMR, 13C-NMR, FT-IR and MS. The synthetic compounds were examined through molecular docking studies on TNF-α for probable binding mode and interactions with hydrophilic and hydrophobic pocket of TNF-α in comparison to standard drug (Indomethacin). Compounds 18, 15 and 9 produced comparable in-vitro TNF-α inhibition and in-vivo inflammatory activity when compared to the standard drug along with no damage to stomach and with reduction of LPO. The compounds 18, 15 and 9 might be a good consideration for potential anti-inflammatory agents.