Noscapine anticancer drug designed with ionic liquids to enhance solubility: DFT and ADME approach

Noscapine is an alkaloid based on the isoquinoline ring with many promising biological potential. Noscapine and its derivatives have shown potential as cough suppressant, anti-cancerous activity, ability to inhibit the main protease of SARS-CoV-2 and non-structural protease of chikungunya etc. Literature has reported the problem of solubility of noscapine due to high hydrophobic character, therefore, poorly soluble in water. In view of this, there is a need to find way to increase the solubility of noscapines. Ionic liquids (11s) are organic salts and considered to have no or permissible toxicity. In the present work, authors report the designing of the ionic liquids (ILs) composed of noscapinium as cation with the different anions. Further, the designed noscapine based ionic liquids were studied using density functional theory (DFT) approach and time dependant density functional theory (TD-DFT). The thermo-chemical data of the designed ionic liquids revealed the stability and reactivity of Its. Further, the IR and UV-visible spectra of the designed ILs were determined and analyzed. Then, the ADME behavior of designed ILs was calculated and studied using online servers. Based on the DFT calculations performed, (R)-5-((S)-4,5-dimethoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6,6-dimethyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-6-ium trifluoromethanesulfonate (IL4) is found to be most soluble in the water and most stable amongst the designed ILs. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Noscapine and its derivatives have shown potential as cough suppressant, anti-cancerous activity, and ability to inhibit the main protease of SARS-CoV-2 and chikungunya. This study focused on designing ionic liquids composed of noscapinium cation with different anions, and analyzing their thermo-chemical data, IR and UV-visible spectra, and ADME behavior. The most soluble and stable ionic liquid among the designed ILs was found to be (R)-5-((S)-4,5-dimethoxy-3-oxo-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6,6-dimethyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-6-ium trifluoromethanesulfonate (IL4) based on DFT calculations.