Solid-phase reactive chromatography (SPRC): a sustainable method for the synthesis of benzimidazol-diphenyl-2-imino-thiazolidine-4-ols (hemiaminals) which are active against lung cancer

Abstract

The concept of a green approach has been applied in the reaction, separation and solidification of a single unit. The products, 2-benzimidazol-diphenyl-2-imino-thiazolidine-4-ols, are purely hemiaminals. They have a tendency to decompose at a high rate. The solid-phase reactive chromatographic technique has been applied to avoid extensive liquid–liquid extraction and stabilised the product by precipitation in solvents. Benzimidazole phenyl thiourea and phenacyl bromide have been used as starting materials in this study. Both the starting materials are adsorbed on dry silica and packed in a glass column with a systematic arrangement of layers. A directly solid product was precipitated in cold hexane. Anticancer activities have been recorded against four cell lines, human colon, prostate, lung and breast cancer, with reference to doxorubicin as a standard. These compounds show a promising effect on human lung cancer, products B9 (IC₅₀ = 3.890 μM) and B10 (IC₅₀ = 2.798 μM) and B13 (IC₅₀ = 3.140 μM) which very close to doxorubicine (IC₅₀ = 1.750 μM). It was observed that fluoro phenyl functionalities are effective compared to trifluoro methyl phenyl functionalities for anticancer activities. These small molecules lose their activities, except fluorination, on bulky substitution. This convenient metal-free approach is highly efficient for unstable hemiaminals such as the potent anticancer benzimidazol-diphenyl-2-imino-thiazolidine-4-ols.