Background: Cancer is the leading cause of death in the current decade. With the advancement
in scientific technologies various treatments had been introduced but they suffer from
numerous side effects. The root cause of cancer is alteration in the cell cycle which generates cancerous
cells. Development of new lead which specifically target cancerous cells is needed to reduce
the side effect and to overcome multidrug resistance.
Objective: Design and development of anticancer leads targeting colchicine site of microtubules using
structurally screened phytofragments is the primary objective of this work.
Materials and Methods: Bioactive fragments of phytoconstituents were identified from a large dataset
of phytochemicals. The identified phytofragments were used to design structures which were
screened for virtual interactions with colchicine site of microtubules. Selected set of designed molecules
was further screened for drug like properties and toxicity. The designed molecules which
surpassed virtual filters were synthesized, characterized and further screened for anticancer potential
against HEPG2 liver cancer cell line.
Results: A novel series of chalcones was designed by phytofragment based drug design. Synthesized
compounds showed profound anticancer activity comparable to standard, 5-fluoro uracil. In
the present communication, rational development of anticancer leads targeting colchicine site of
microtubules has been done by integrating pocket modeling and virtual screening with synthesis
and biological screening.
Conclusion: In this present work, we found that compounds S4 and S3 showed specific interaction
with colchicine site of microtubules and desirable anticancer activity. Further optimization of the
lead could yield drug like candidate with reduced side effects and may overcome multidrug resistance.