The aim of this study is to incorporate both arylcinnamide and stilbene moieties into a hybrid and
evaluated for cytotoxicity against A549 lung cancer cells. Several frameworks on stilbene-cinnamoyl hybrid
have been reported with their high capacity as an anticancer agent and have been reported as tubulin polimerization
inhibitor. In the present work, the most active compound was further studied via in silico molecular
docking on α,β-interface of tubulin. Stilbene and cinnamic acid have played a commendable role in drug discovery
as they have shown high effectiveness in chemoprevention and chemotherapeutic effects on cancers
through several mechanisms. Several frameworks on stilbene-cinnamoyl hybrid have been reported with their
high capacity as an anticancer agent and reported as tubulin polimerization inhibitor. In this project, we synthesized
a series of stilbene-cinnamoyl hybrid, cytotoxic activity, and molecular docking on the binding site of
tubulin protein. The objectives of this study are to synthesize the stilbene-cinnamoyl hybrid, evaluated for cytotoxicity
against A549 lung cancer cells and to study the molecular docking of active compounds to α,β- tubulin.
A new series of stilbene-arylcinnamide hybrids have been designed and synthesized with various substituents.
These compounds were characterized by FTIR, 1D- and 2D-NMR as well as mass spectroscopy analysis
(HRESIMS). The synthesized compounds were tested for their cytotoxic activity against human lung cancer
A549 cell. The most active compound was further studied via in silico molecular docking on α,β-interface of
tubulin.
Total 18 new stilbene-arylcinnamide hybrids have been synthesized with 42-80% yield and evaluated for their
cytotoxic activity against human lung cancer A549 cell. Particularly, compound 6b exhibited potent cytotoxicity
against A549 cells with the IC50 value of 19.9 μM. In addition, compound 7b displayed moderate activities
with the IC50 value of 33.9 μM, while other hybrids were considered inactive. Structural activity relationship
(SAR) studies revealed that the presence of an isopropyl group at the para position on ring A and a methyl
group at the para position on ring C is beneficial for enhanced cytotoxicity.
Furthermore, we also developed an in silico molecular docking to study the binding interaction of the active
compounds to the α,β-interface of tubulin (PDB ID: 3E22). Hybrids 6b and 7b demonstrated promising binding
interactions and affinities into the tubulin active site with calculated binding energy of -7.2 and -8.0 kcal/mol,
respectively.
