Phytochemical and Pharmacophoric Fragment Based Anticancer Drug Development

Abstract

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. Material 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 then synthesized, characterized and further screened for anticancer potential against HEPG2 liver cancer cellline. Result: A novel series of chalcones was designed by phytofragment based drug design. The 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 compound 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.

Fragment-Based Approach towards the Design of Potent and Versatile Anti-Cancer Agents

“…The main objective of phytochemical and pharmacophoric fragment based anticancer drug development is to design new anticancer leads that are capable of targeting cancer cells by using phytofragments that have been structurally screened. This technology has resulted in the lead compounds that may act as drug candidates showing less side effects and that may aid in the reduction of multidrug resistance (Rochlani et al, 2020).…”

Fucosyltransferase 2 inhibitors: Identification via docking and STD-NMR studies

“…In particular, FBDD identify low molecular weight compounds that serve as starting points for drug designing against biomolecular drug targets [ 18 , 19 ]. Several drugs have been developed through the FBDD approach [ 20 ], and approved by US-FDA [ 21 ]. We have performed the computational fragment-based approaches, such as molecular docking studies, followed by the biophysical techniques i .…”