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Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones : synthesis, biological activity, crystal structure analysis, and molecular docking studies

Siti Munirah, Mohd Faudzi and Maryam Aisyah, Abdullah and Mohd Rashidi, Abdull Manap and Ahmad Zaidi, Ismail and Kamal, Rullah and Mohd F. F., Mohd Aluwi and Aizi Nor Mazila, Ramli and Faridah, Abas and Nordin, Lajis (2020) Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones : synthesis, biological activity, crystal structure analysis, and molecular docking studies. Bioorganic Chemistry, 94 (103376). pp. 1-12. ISSN 0045-2068

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Abstract

In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 – 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ± 1.5 µM and 12.1 ± 1.5 µM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single-crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.

Item Type: Article
Additional Information: Indexed by Scopus
Uncontrolled Keywords: Anti-inflammatory agents; Chalcone derivatives; Inflammation
Subjects: T Technology > TP Chemical technology
Faculty/Division: Faculty of Industrial Sciences And Technology
Depositing User: Mrs Norsaini Abdul Samat
Date Deposited: 23 Dec 2020 04:30
Last Modified: 23 Dec 2020 04:30
URI: http://umpir.ump.edu.my/id/eprint/27773
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