Computer-Based Ligand Design and Synthesis of Some New Sulfonamides Bearing Pyrrole or Pyrrolopyrimidine Moieties Having Potential Antitumor and Radioprotective Activities

Abstract

A series of new Pyrrole and pyrrolo[2,3-d]pyrimidine derivatives ( 5–15 ) was designed, synthesized, and biologically evaluated for their in vitro cytotoxic activity. The design of these compounds was based upon the molecular modeling simulation of the fitting values and conformational energy values of the best-fitted conformers to VEGFRTK inhibitors hypothesis. This hypothesis was generated from its corresponding lead compounds using CATALYST software. Some of the newly synthesized compounds 8 , 11 , 12 , and 13 showed interesting cytotoxic activity compared with Doxorubicin as a reference drug. These results are nearly consistent with the molecular modeling studies. Moreover, Compound 7 showed significant radioprotective activity.

Keywords:

• Pyrrole
• pyrrolo[2,3-d]pyrimidine
• molecular modeling studies
• synthesis
• tyrosine kinase inhibitors
• antitumor and radioprotective activities

Notes

*IC ₅₀ value which corresponds to the compound concentration causing 50% mortality in net cells.

***very high significance at P < 0.001.; CMC: carboxy methyl cellulose.