Pharmacophore Screening and Molecular Docking of Phytoconstituents in Polygonum Sagittatum for Cyclooxygenase-2 Inhibitors Discovery.

Abstract

Objective: The objective of this study is to discover cyclooxygenase (COX-2) inhibitors from Polygonum sagittatum (Polygonaceae), by screening the pharmacophores based on the interaction of mefenamic acid with COX-2, followed by molecular docking with COX-2. Methods:The protein crystal structure of human COX-2 in complex with mefenamic acid (PDB code: 5IKR) was selected, its ligand-protein interaction was studied by employing LigandScout to obtain the pharmacophore features. The features were validated against PGH2 database provided at http://dude.docking.org/targets/pgh2, and the result was used to screen the pharmacophores of the phytoconstituents isolated from P. sagittatum. Furthermore, a molecular docking of the phytoconstituents into COX-2 binding pocket was performed. The compounds were generated using MarvinSketch, and the energy was optimized by employing LigandScout MMFF94. Celecoxib and mefenamic acid, selective COX-2 inhibitors, were used as the standard drugs. Results:The pharmacophore features obtained were aromatic ring (hydrophobicity) and two hydrogen bond acceptors, which are proved valid against PGH2 training set (GH score = 0.78; AUC 100% receiver operating characteristic curve = 0.97). There are four phytoconstituents (quercetin, protocatechuic acid, vanicoside A, and vanicoside B) that fit the features, and therefore, are predicted to be active in inhibiting COX-2. The docking reveals that three phytoconstituents (methyl-4-hydroxycinnamate, quercetin, and methyl gallate) interact with Tyr385, an important amino acid residue in COX-2 binding pocket. Quercetin is the best in inhibiting the enzyme (docking score −8.60 kcal/mol; inhibition constant 0.5 µM), compared to mefenamic acid (docking score −8.90 kcal/mol; inhibition constant 0.3 µM) and celecoxib (docking score −10.00 kcal/mol; inhibition constant 0.05 µM).Conclusions: Phytoconstituents in P. sagittatum fit the pharmacophore features generated from mefenamic acid and COX-2 complex; therefore, they might be potential in inhibiting COX-2 enzyme. Their binding modes are more similar to that of mefenamic acid than of celecoxib. Of those, quercetin is the best in inhibiting the enzyme. Its inhibitory activity is equal to mefenamic acid but is weaker than celecoxib.

Potensi Antibakteri Ekstrak Metanol dan Senyawa Aromatik dari Buah Wualae (Etlingera elatior)

“…Kajian aspek kimia dan farmasi tanaman obat tradisional masyarakat Sulawesi Tenggara terus menerus dilakukan di Fakultas Farmasi Universitas Halu Oleo. Beberapa tanaman yang telah dipelajari antara lain Dipterocarpaceae (Juliawaty et al, 2009;Sahidin et al, 2017), Euphorbiaceae (Sahidin et al, 2011;Sahidin et al, 2013;Sabandar et al, 2013), Fabaceae (Al Muqarrabun et al, 2013), Poaceae (Ruslin et al, 2013), Polagonaceae (Sahidin et al, 2014;2015;Megantara et al, 2018;Ahmad et al, 2018), anacardiaceae (Wahyuni et al, 2018) dan Zingiberaceae (Sahidin et al, 2018).…”

Phytochemical Profile and Biological Activities of Ethylacetate Extract of Peanut (Arachis hypogaea L.) Stems: In-Vitro and In-Silico Studies with Bibliometric Analysis

“…In continuing our group's research on traditional medicinal plants in Southeast Sulawesi, we are interested in studying the peanut plant, which local people use as food and traditional medicine. Several traditional medicinal plants that have been studied previously include Imperata cylindrical (Ruslin et al, 2013), Polygonum (Sahidin et al, 2014(Sahidin et al, , 2015Sadino et al, 2016Sadino et al, , 2017Megantara et al, 2018;Ahmad et al, 2018), Persicaria (Sahidin et al, 2019) and Etlingera (Sabilu et al, 2017;Sahidin et al, 2018, Grashella et al, 2019, 2021a, 2021bFristiohady et al, 2020aFristiohady et al, , 2020bFristiohady et al, , 2021Yusuf et al, 2021aYusuf et al, , 2021bImran et al, 2022).…”

Antibacterial and antioxidant potentials of methanol extract and secondary metabolites from Wualae rhizome (Etlingera elatior)

“…Study on the phytochemical and pharmacological aspects of the traditional medicinal plants in Southeast Sulawesi are continuously undergoing at the Halu Oleo University, Faculty of Pharmacy. Some of the plants that have been studied including Dipterocarpaceae (Juliawaty et al, 2009;Sahidin et al, 2017), Euphorbiaceae (Sahidin et al, 2011;Sahidin et al, 2013;Sabandar et al,, 2013), Fabaceae (Al Muqarrabun et al, 2013), Poaceae (Ruslin et al, 2013), Poligonaceae (Sahidin et al, 2014;2015;Megantara et al, 2018;Ahmad et al, 2018), Anacardiaceae (Wahyuni et al, 2018) and Zingiberaceae . Wualae (Tolakinese) or Etlingera elatior (Zingiberaceae) contains non-volatile and volatile compounds which are interesting to study.…”