NOVEL SUBSTITUTED 2’- PROP-1-EN-2-YL)- 1’, 2’, 3’, 4’- TETRAHYDRO-[1, 1’- BIPHENYL]- 2, 6- DIOL COMPOUNDS AS ADENOSINE A2A RECEPTOR ANTAGONISTS: INDUCED-FIT MOLECULAR DOCKING STUDIES AND PHARMACOKINETIC PREDICTIONSAbstract
Adenosine release is more apparent after seizures or in-vitro seizure-like activity and tissue adenosine level increases quickly after seizure commencement. These adenosine increases linked to seizures are reflections in composing a response mechanism that controls seizure intensity and duration. Much evidence from animal studies suggests that this impact is mediated by the adenosine receptor (AR), just as it is with neurotransmission in general. Efforts to produce centrally acting treatments and reduce peripheral side effects, especially cardiac adverse effects, have long been prioritized in drug development. New study is targeting highly precise areas of the A2R might be a step forward in direct A2R-based anti-seizure therapy. Despite significant attempts to introduce innovative tactics for the treatment of various kinds of epilepsy, this illness continues to be a serious problem across the globe. Taking inspiration from the facts above and recognizing the growing need for anti-epileptic compounds with improved pharmacodynamics and pharmacokinetic profiles in the worldwide market. The present in-silico research involves studying the anti-convulsant (anti-epileptic) potentials of some substituted 2′-(prop-1-en-2-yl)-1′,2′,3′,4′-tetrahydro-[1,1′-biphenyl]-2,6-diol molecules (A1 to A16) by exploring the adenosine A2A receptor (A2AR) [PDB ID: 4EIY] inhibition through induced-fit molecular docking approach, employing Schrodinger Maestro v.12.8 software. By directing medicinal chemists toward exploring novel compounds, this in-silico study opened the way for novel anti-epileptic drug development by identifying novel A2AR inhibitors, which play an essential function in managing convulsions. These solutions to synthetic compounds’ never-ending search for superior anti-convulsant activity would open new avenues.
Sunil Kumar, Sucheta *, Arun Garg, Nidhi Dhama and Abhishek Mathur
School of Medical and Allied Sciences, K. R. Mangalam University, Gurgaon, Haryana, India.
03 March 2022
17 May 2022
26 May 2022
01 July 2022