Greener approach for synthesis of novel steroidal prodrugs using ionic liquid, their DFT study and apoptosis activity in prostate cancer cell line
| Autor: | Ranvijay Pratap Singh, Praveer Singh, Arun Sethi, Monisha Banerjee, Neera Yadav, Priyanka Yadav |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Mefenamic acid
010405 organic chemistry Organic Chemistry Acridine orange Diosgenin Prodrug 010402 general chemistry 01 natural sciences Combinatorial chemistry 0104 chemical sciences Analytical Chemistry Inorganic Chemistry chemistry.chemical_compound chemistry Ionic liquid medicine Molecule MTT assay Reactivity (chemistry) Spectroscopy medicine.drug |
| Zdroj: | Journal of Molecular Structure. 1180:733-740 |
| ISSN: | 0022-2860 |
| DOI: | 10.1016/j.molstruc.2018.12.009 |
| Popis: | In the present work Ionic liquid (IL), N-methyl-2-pyrolidonehydrogensulphate, (NMP+HSO4−) has been used as the green catalyst for the synthesis of novel biologically active diosgenin prodrugs 2 and 3. The prodrugs were synthesized by coupling of non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and mefenamic acid with diosgenin in the presence of ionic liquid (NMP+HSO4−). A high conversion of diosgenin (90%) and prodrugs yield (86.57 ± 1.78%) were achieved using (NMP+HSO4−) as catalyst under the following conditions: 40 °C, NSAID/diosgenin 1:1 (mol/mol), catalyst load (47.56 mg, 0.241 mmol). Re-usability test showed that (NMP+HSO4−) catalyst has excellent utility for repeated use, the ease of its separation from reaction mixture by simple filtration, is thus beneficial from economical point of view. Diosgenin along with its prodrugs 2 and 3 were investigated for cytotoxicity and apoptosis through MTT assay and ethidium bromide/acridine orange (EB/AO) staining, respectively, of prostate cancer cell line PC-3. The results were very promising as these prodrugs have shown significant anticancer activity against prostate cancer cells. Density functional theory (DFT) studies were also carried out for prodrugs 2 and 3 using B3LYP/6-31G (d,p) basis set. Intramolecular interactions were analysed by AIM (Atoms in Molecule) approach. Molecular electrostatic potential surface (MEPS) was used to indicate nucleophilic and electrophilic sites. Electronic properties such as HOMO-LUMO energies were measured with the help of time dependent DFT method. Global reactivity descriptors of prodrugs 2 and 3 were also calculated. |
| Databáze: | OpenAIRE |
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