A Profile of the In Vitro Anti-Tumor Activity and In Silico ADME Predictions of Novel Benzothiazole Amide-Functionalized Imidazolium Ionic Liquids

Abstract

A focused array of green imidazolium ionic liquids (ILs) encompassing benzothiazole ring and amide linkage were designed and synthesized using quaternization and metathesis protocols. The synthesized ILs have been fully characterized by usual spectroscopic methods and screened for their anticancer activities against human cancer cell lines originating from breast and colon cancers. Collectively, our biological data demonstrate that the newly synthesized series has variable anticancer activities in the examined cancer types. The synthesized ILs 8, 10 and 21–29 comprising the methyl and methyl sulfonyl benzothiazole ring emerged as the most potent compounds with promising antiproliferative activities relative to their benzothiazole ring counterparts. Furthermore, the mechanism underlying the observed anticancer activity was investigated. The most active compound 22 appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound 22 has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.

Mechanisms of action of ionic liquids on living cells: the state of the art

“…In this cell line, four AChE monomers are organized in a globular tetramer directed onto the membrane surface for its cholinergic function by a membrane anchor protein. Inhibition of p-glycoprotein, which is a plasma membrane protein exporting drugs out of the cell, has been observed in several human cancer cell lines originating from breast and colon cancers after incubation in a series of newly synthesized imidazolium ILs tethered benzothiazole moieties with fluorinated counter anions (Al-blewi et al 2019 ). Inhibition of the Na-K-ATPase, an enzyme located onto the cell membrane and responsible for cell growth by regulating the in and out transport of, respectively, K + and Na + ions has been observed in CCO cells incubated in [C n mim][NTf 2 ] ILs (Radošević et al 2013 ; Stolte et al 2006 ).…”

“…Inhibition of p-glycoprotein, which is a plasma membrane protein exporting drugs out of the cell, has been observed in several human cancer cell lines originating from breast and colon cancers after incubation in a series of newly synthesized imidazolium ILs tethered benzothiazole moieties with fluorinated counter anions (Al-blewi et al 2019 ).…”

“… Apoptosis has been observed in NIH/3T3 cells incubated in [C 4 mim][Cl] and [C 4 mim][Gly] (Egorova et al 2015 ). Apoptosis has been observed in T47D cells incubated in a series of newly synthesized imidazolium-tethered benzothiazole moieties with fluorinated counter anion ILs (Al-blewi et al 2019 ). Interestingly, none of the targeted compound was able to permeate through the blood-brain barrier.…”

Carboxamide appended quinoline moieties as potential anti-proliferative agents, apoptotic inducers and Pim-1 kinase inhibitors

“…A suitable physiochemical vector for the regulation of drug transportation characteristics is the TPSA (Topological Polar Surface Area). It was tried to forecast the absorption rate of all test molecules by the reporting equation (ABS = 109-(0.345 X TPSA) [47].…”

Novel Dipyridinium Lipophile-Based Ionic Liquids Tethering Hydrazone Linkage: Design, Synthesis and Antitumorigenic Study

“…As part of our ongoing progress in the field of potent ionic liquid frameworks bearing pyridine-hydrazone [ 16 , 17 , 18 , 19 ], these features have significantly improved our structural and functional expertise. Thus, we attempt in the present work to provide the design, synthesis and characterization of an array of dicationic pyridinium hydrazone incorporating long alkyl side chains.…”