Synthesis, Experimental and Density Functional Theory (DFT) Studies on Solubility of Camptothecin Derivatives

Molecules. 2018 Dec 1;23(12):3170. doi: 10.3390/molecules23123170.

Abstract

Two camptothecin derivatives, 10-cyclohexyl-7-methyl-20(S)-camptothecin and 7-methyl-10-morpholino-20(S)-camptothecin, were synthesized and their differences in solubility were investigated using four chosen solvent systems. Based on our results, 10-cyclohexyl-7-methyl-20(S)-camptothecin exhibited higher solubilities than 7-methyl-10-morpholino-20(S)-camptothecin in polar aprotic solvents. However, these two camptothecin derivatives did not exhibit apparent differences in solubility between 5% dimethyl sulfoxide (DMSO)/95% normal saline co-solvent system and 5% dimethylacetamide (DMAC)/95% normal saline co-solvent system. To rationalize their differences in solubility, we also tried to perform a DFT-B3LYP study to investigate their interaction with one water molecule.

Keywords: DFT; acid-catalyzed; camptothecin; condensation; solubility.

MeSH terms

  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemical synthesis
  • Camptothecin / chemistry*
  • Chemistry Techniques, Synthetic
  • Density Functional Theory
  • Models, Molecular
  • Molecular Structure
  • Solubility
  • Solvents

Substances

  • Solvents
  • Camptothecin