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Updated: Dec 28, 2025
NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
Published on: June 4, 2021
Phytochemical and Pharmacophoric Fragment Based Anticancer Drug Development
S P Rochlani1, L K Dahiwade1, P B Choudhari1
1Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India.
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.
Insights
Researchers developed novel anticancer compounds targeting microtubules by screening plant fragments. Compounds S4 and S3 demonstrated significant anticancer activity, offering potential for new cancer treatments with fewer side effects.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Cancer remains a leading cause of death globally, with current treatments often causing significant side effects and facing challenges with multidrug resistance.
- Cancer arises from alterations in the cell cycle, necessitating the development of novel therapeutic agents that specifically target cancerous cells.
Purpose of the Study:
- To design and develop novel anticancer drug leads that target the colchicine binding site on microtubules.
- To utilize structurally screened phytofragments for the rational design of these anticancer agents.
Main Methods:
- Identification and screening of bioactive phytofragments from a phytochemical database.
- Virtual screening of designed molecules for interaction with the colchicine site of microtubules.
- Synthesis, characterization, and in vitro anticancer evaluation against HEPG2 liver cancer cells.
Main Results:
- A new series of chalcone-based compounds were designed using a phytofragment-based drug design approach.
- Synthesized compounds exhibited potent anticancer activity, comparable to the standard drug 5-fluorouracil.
- Compounds S4 and S3 demonstrated specific interactions with the colchicine site of microtubules.
Conclusions:
- Compounds S4 and S3 show promising anticancer activity and specific interaction with the colchicine site of microtubules.
- These compounds represent potential lead candidates for further optimization to develop drugs with reduced side effects and improved efficacy against multidrug-resistant cancers.
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