In silico study, synthesis and evaluation of Pharmacological potential of some Kynurenic acid analogues provide sub Headings for writing
Akshita Garg1*, MK Gupta2 , Nidhi Khatri3 , Bhanu Pratap Singh3 and Ritu Sharma
1,2Department of pharmacy Career point university, Alaniya, Kota - 325003 (India) 3University Institute of Pharmaceutical Education and research, University of Kota, Kota - 324005 (India) 4Career point university, Alaniya, Kota - 325003 (India) Corresponding Author: Akshita Garg, P. G. Scholar, Department of Pharmacy Career Point University, Alaniya, Kota - 325003 (India)
ABSTRACT
The present study explores the in silico design, synthesis, and pharmacological evaluation of novel kynurenic acid (KYNA) analogues with improved neuroprotective, anti-inflammatory, and antioxidant properties. Kynurenic acid, a metabolite of the tryptophan-kynurenine pathway, exhibits promising neuromodulatory and antioxidant activities but suffers from poor bioavailability and limited brain penetration. Using computational modeling and ADMET predictions, several KYNA analogues were designed and evaluated for drug-likeness, receptor binding (especially NMDA and KAT-II), and pharmacokinetics. Among the synthesized compounds, KA-5 and KA-3 emerged as top candidates based on docking scores, high gastrointestinal absorption, and bloodbrain barrier permeability. In vitro assays demonstrated significant antiinflammatory and antioxidant activity, with KA-5 showing 84.7% DPPH scavenging and 81.4% protein denaturation inhibition—comparable to reference drugs. Neuroprotective potential was confirmed on SH-SY5Y neuroblastoma cells, with KA-5 and KA-3 showing over 60% viability. Overall, KA-5 stood out with a mean final score of 4.8, indicating its potential as a CNS-targeted therapeutic agent. This integrated approach highlights the value of computational-experimental synergy in modern drug discovery for neurological disorders