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

• Published in: International journal of molecular sciences Vol. 20; no. 12; p. 2865
• Main Authors: Al-Blewi, Fawzia, Rezki, Nadjet, Naqvi, Arshi, Qutb Uddin, Husna, Al-Sodies, Salsabeel, Messali, Mouslim, Aouad, Mohamed Reda, Bardaweel, Sanaa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-06-2019; MDPI
• Subjects: Acetonitrile; ADME; Alkylation; Anion exchanging; Anions; anticancer; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzothiazole; Benzothiazoles - chemistry; Bioavailability; Cancer; Cell Line, Tumor; Cell Proliferation - drug effects; Chemical Phenomena; Dichloromethane; Drug development; Fluorine; Humans; Imidazole; Imidazoles - chemistry; Imidazoles - pharmacokinetics; Imidazoles - pharmacology; Investigations; Ionic liquids; Ionic Liquids - chemistry; Ions; Magnetic Resonance Spectroscopy; Metabolism; Metathesis; Nitrogen; Organic chemistry; Pharmaceutical industry; Pharmacokinetics; Physicochemical properties; Refluxing; Salts; Solvents; Substitutes; ionic liquids; imidazole; ADME; benzothiazole; anticancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20122865

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
,
and
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
appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound
has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.