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

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 12; p. 3170
• Main Authors: Lai, Chin-Hung, Chang, Chia-Chin, Weng, Yi-Lin, Chuang, Ta-Hsien
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2018; MDPI
• Subjects: acid-catalyzed; camptothecin; Camptothecin - analogs & derivatives; Camptothecin - chemical synthesis; Camptothecin - chemistry; Cancer; Chemistry Techniques, Synthetic; Clinical trials; condensation; Density Functional Theory; DFT; Hydration; Hydrogen bonds; Models, Molecular; Molecular Structure; Nitrogen; Pharmacokinetics; Solubility; Solvents; condensation; solubility; DFT; camptothecin; acid-catalyzed
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23123170

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.