Synthesis of Novel Aryl (4-Aryl-1H-Pyrrol-3-yl) (Thiophen-2-yl) Methanone Derivatives: Molecular Modelling, In Silico ADMET, Anti-Inflammatory and Anti-Ulcer Activities

Abstract

Background:: A series of novel aryl (4-aryl-1H-pyrrol-3-yl) (thiophen-2-yl) methanone derivatives was synthe-sized from sequential addition reaction with chalcones and toluenesulfonylmethyl isocyanide (TosMIC). Methods: The de-rivatives were screened against anti-inflammatory, anti-ulcer activities with an inhibition of 80.65% for PY-5 compound at 200mg/kg and inhibition of 77.5% for PY-1 compound at 200mg/kg. Active anti-inflammatory agents were subjected to in-vitro Cyclooxygenase (COX) inhibition assay. The interactions between the synthesized compounds and active site residues of proteins COX-1 (3N8Y), COX-2 (1PXX), H+/K+ ATPase (2XZB) were investigated by using molecular docking studies using autodock 4.2. Results and Conclusion:: In silico drug likeliness and toxicity prediction studies were carried by OSIRIS property explorer and admetSAR prediction tool which predicts that two compounds of PY-5 and PY-1 shows a new class of potential anti-inflammatory and anti-ulcer agents and serves as new anti-inflammatory and anti-ulcer drugs after further investigation.

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

“…Targeting COX-2, NF-kB, STAT3, and histone acetylation involved in the inflammatory process could represent a good strategy for anti-inflammatory activity, cancer prevention, and therapy. [151][152][153][154][155][156][157]…”

“…Many other heterocycles have been reported for their anticancer and anti‐inflammatory activity. Targeting COX‐2, NF‐κB, STAT3, and histone acetylation involved in the inflammatory process could represent a good strategy for anti‐inflammatory activity, cancer prevention, and therapy [151–157] …”