Design, Synthesis, Cytotoxic Effect Evaluation and Molecular Docking of (R)‐Camphor‐Based Thiazolidinone‐Isoxazole and Thiazolidinone‐1,2,3‐triazole Hybrids“

Abstract

AbstractA variety of hybrid compounds, combining a camphor thiazolidinone skeleton with either 1,2,3‐triazole or isoxazole nucleus, have been synthesized from natural (R)‐camphor. Our efficient procedure consists in a transformation of the (R)‐camphor into the corresponding thiazolidin‐4‐one. The latter is then N‐alkylated with propargyl bromide before submitting the resulting product to 1,3‐dipolar cycloaddition reactions, with a series of nitrile oxides and arylazides respectively. The chemical structures of all the newly synthesized hybrids were established using (1H and 13C) NMR and HRMS analysis. Preliminary in‐vitro cytotoxic assays on three human cancer cell lines MCF‐7 (breast), A‐549 (prostate) and HT‐1080 (fibrosarcoma) were performed on all the compounds. The thiazolidinone‐1,2,3‐isoxazole hybrid 8 c was revealed to be the most active with IC50 values ranging from 11.62±4.52 μM to 16.92±1.22 μM against selected cancer cells. Molecular docking studies carried out on the three compounds 8 c, 9 a and 9 c, confirmed, as expected, that these compounds possess a great inhibition potential against BCl‐2 protein, Caspase‐3 and COX‐2 enzymes. The results showed that the selected compounds had a significant binding property which could lead to the development of novel BCl‐2, Caspase‐3 and −2 inhibitors with improved selectivity. Finally, an ADME study was applied and proved the promising activity of the new compounds as a new oral anti‐inflammatory agent.