Microwave Assisted Synthesis, Biological Evaluation and In-silico Molecular docking and Pharmacokinetic Studies of Novel Heterocyclic Hybrid Dihydropyrazol-1-yl-2-(Quinolin-8-yloxy) Derivatives
Waikhom Somraj Singh
Natural Cum Advance Synthetic Lab, Department of Pharmacy, Tripura, India University (A Central University), Suryamaninagar, Agartala-799022, Tripura, India.
Kuntal Manna *
Natural Cum Advance Synthetic Lab, Department of Pharmacy, Tripura, India University (A Central University), Suryamaninagar, Agartala-799022, Tripura, India.
*Author to whom correspondence should be addressed.
Abstract
A novel heterocyclic hybrid dihydropyrazol-1-yl-2-(quinolin-8-yloxy) derivatives were synthesized. By reacting 8-hydroxyquinoline 1 in absolute ethanol with potassium carbonate followed ethyl chloroacetate by conventional and microwave irradiation methods, precursor 2 were synthesized, further treated with hydrazine hydrates to achieve precursors 3 and by Claisen-Schmidt condensation methods, different chalcone derivatives 6(a-g) were prepared and to these precursors 3 was then cyclized to give the target compounds 7(a-g). The structures of the target compounds were evaluated by the spectral and elemental method of analysis. The screened compounds 7a and 7g produced better action than other compounds but somewhat lesser than the standard drugs. Furthermore molecular docking studies have been carried out against PDB codes: 5MTX (p38 MAPK) using Biovia Discovery Studio 2021. The compounds 7a (-8.947 Kcal/mol) and 7g (-8.994 Kcal/mol) had shown remarkable binding affinities which were greater than the binding affinity of recommended drugs; diclofenac sodium (-6.8 kcal/mol), and nimesulide (-7.8 kcal/mol).
Keywords: Dihydropyrazol-1-yl-2-(quinolin-8-yloxy) derivatives, molecular docking, pharmacokinetics, in-vitro anti-inflammatory, in-vitro antioxidant, p38 MAPK