Abstract
A series of eleven flavone derivatives were synthesized. The synthesized compounds were characterized structurally by various techniques using spectral analyses. All of the synthesized compounds were subjected to MTT proliferation assay to investigate their in-vitro cytotoxic activity. Among all the studied compounds, compounds, VIi, VIh, VId and VIk revealed moderate growth inhibitory effect towards the MDA-MB 231 cell line compared to the reference, doxorubicin. These compounds showed cytotoxicity activity with IC50 values ranging from 43.7 to 138 µM in MDA-MB 231 cell line. The results of cytotoxic activity revealed that flavone derivatives with N-aryl acetamide substituted at the 3-position of flavone backbone have better cytotoxic activity. Moreover, the highest activity was observed with compound VIi that has oxy-N-pyriden-2-yl acetamide substituent at the 3-position of flavone backbone followed by compound VIh with IC50 values of 43.7 and 50 μM, respectively. The biological activity results were elucidated by molecular docking studies using the homology model of the human adenosine A2B receptor. As a result, the present study has highlighted that the bicyclic moiety of the compounds attached to hydrogen bond donor-acceptor capability and π-π stacking is an attractive scaffold for obtaining cytotoxic activity.
Highlights
G-protein coupled receptors (GPCRs) are one of the most common types of membrane bound receptors
GPCRs are targets in many recent pharmaceutical researches which focused on drug discovery
The hit compound produced from virtual screening based on homology model of the human A2B Adenosine receptors (ARs) has been made by retrosynthetic analysis
Summary
G-protein coupled receptors (GPCRs) are one of the most common types of membrane bound receptors They mediate response to diverse natural ligands. Activation of GPCRs result in either rapid response as activation of ion channels or slower one as intracellular enzyme cascades. These events are responsible for different physiological responses [Congreve et al, 2014]. GPCRs are targets in many recent pharmaceutical researches which focused on drug discovery. They are formed from seven membrane spanning α-helices (TM1-7) connected by intracellular (IL1, IL2 and IL3) and extracellular loops (EL1, EL3 and EL3). Nterminal is located extracellular and C-terminal is positioned intracellular and maintain interaction with cytosolic G-protein (Figure 1)
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