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Current Computer-Aided Drug Design


ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Phytochemical and Pharmacophoric Fragment Based Anticancer Drug Development

Author(s): S.P. Rochlani*, L.K. Dahiwade and P.B. Choudhari

Volume 17, Issue 1, 2021

Published on: 12 February, 2020

Page: [22 - 31] Pages: 10

DOI: 10.2174/1573409916666200212122445

Price: $65


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.

Keywords: Phytoconstituents, colchicine, microtubules, anticancer, fragment based drug design, chalcone.

Graphical Abstract
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