Synthesis, molecular docking and pharmacological evaluations of novel naphthalene-pyrazoline hybrids as new orally active anti-inflammatory agents

Abstract

The pyrazoline nucleus is widely present in diverse compounds as it serves as a valuable template for the discovery of new class of bioactive compounds. Various substituted 2-pyrazolines exhibit a spectrum of pharmacological activities, including antimicrobial, anti-inflammatory, analgesic, and antitumor properties. In view of this, we have synthesized a novel class of naphthalene-pyrazoline hybrids (PY1-PY20). All the synthesized hybrids were thoroughly characterized by means of standard spectroscopic techniques and tested for their in-vivo anti-inflammatory activity. Most of the compounds exhibited significant anti-inflammatory activity and in particular the compounds bearing electron withdrawing groups had potential in vivo activity. Further, in-silico molecular docking studies were carried out using the ‘Molegro Virtual Docker’ as a docking tool against the target proteins such as COX-1 (PDB ID: 1EQH) and COX-2 (PDB ID: 1PXX). The results revealed that the majority of pyrazolines form hydrogen interactions with key residues (Ser 530, Tyr 385, Tyr 355, Arg 120, Ser 353, Arg 83) in the active binding sites of COX-1 (1EQH) and COX-2 (1PXX). Notably, interactions with residues Tyr 355, Arg 120, Ser 530 for COX-1, and Tyr 355, Arg 120, Gln 192, Leu 352, Ser 353, His 90, Tyr 38, Ser 530, and Tyr 385 for COX-2 are crucial for the reported anti-inflammatory activity of diverse compounds. Ligand-protein inverse molecular docking studies highlight specific hydrogen bond interactions, with PY-8, PY-11, PY-15, and PY-17 showing significant interactions. The study was able to identify potential anti-inflammatory naphthalene-pyrazoline derivatives.