In-silico ANALYSIS OF (S)-PINOSTROBINBENZOATE DERIVATIVES FROM Boesenbergia pandurata Roxb. AS THE CYCLOOXYGENASE-2 INHIBITORS IN FINDING ANTI-INFLAMMATORY DRUG CANDIDATES.

Wiyono, A. S.; Diyah, N. W.; Siswandono, S.

Boesenbergia pandurata Roxb. Schlecht, often known as Temu kunci, contains the flavonoid pinostrobin in its rhizome. It is useful against inflammation because it can suppress the cyclooxygenase-2 (COX-2) enzyme. The goal of this work is to develop (S)-pinostrobinbenzoate derivatives, a chemical that inhibits inflammation on COX-2 targets, to use in silico analysis to find possible candidates for anti-inflammatory drugs. In this work, 20 compounds of (S)- pinostrobinbenzoate derivatives were the subject of an in silico investigation using PASS online to predict the substance activity spectrum (PASS) and MOE 2022.02 for molecular docking on the COX-2 enzyme (PDB code 1CX2). The pkCSM Online application was also used to estimate ADMET characteristics. The structure-activity relationships of the selected compounds were examined by the quantitative structure-property relationships (QSPR) approach. The results showed that (S)-pinostrobin 2-methoxybenzoate had a strong affinity for COX-2 based on molecular docking, as indicated by a free binding energy (S value) of -9.16 kcal/mol. From PASS online it was found that a COX-2 inhibitor, has an "active" probability (Pa) of 0.763, giving it a viable option for anti-inflammatory medications. Based on ADMET prediction, (S)-pinostrobinbenzoate derivatives displayed high specificity and sufficient BBB permeability. The QSPR analysis indicated that the lipophilic character (logP) of the (S)- pinostrobinbenzoate derivatives relates to its in-silico activity against COX-2. This work provided a solid basis for subsequent investigations to combine and assess the anti-inflammatory effects in vitro and in vivo, then the pre-clinic and clinical trial pertaining to the development of the (S)-pinostrobinbenzoate.

MOLECULAR docking; STRUCTURE-activity relationships; BINDING energy; CYCLOOXYGENASE 2 inhibitors; CYCLOOXYGENASE 2

Rasayan Journal of Chemistry, 2024, Vol 17, Issue 4, p1802

0974-1496

Academic Journal

10.31788/RJC.2024.1748900