Synthesis, antiproliferative and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors.

As a target for clinical anti-cancer treatment, epidermal growth factor receptor (EGFR) exhibits its over-expression on various tumour cells and is associated with the development of a variety of human cancers. Herein, we described the synthesis, antiproliferative activity assay and 4D-QSAR studies of thiadiazole derivatives bearing acrylamide moiety as EGFR inhibitors. Compared with Gefitinib, some of the target compounds have excellent antiproliferative activities against EGFR-expressed A431 cell line. The robust and reliable 4D-QSAR was constructed using comparative distribution detection algorithm, ordered predictors selection and genetic algorithm method, and the following acceptable statistics are shown: r2 = 0.82, Q2LOO = 0.67, Q2LMO = 0.61, r2Pred = 0.78.

Synthesis and receptor dependent 4D-QSAR studies of 4,5-dihydro-1,3,4-oxadiazole derivatives targeting cannabinoid receptor.

Cannabinoid receptor has been shown to be overexpressed in various types of cancers, especially non-small cell lung cancer. As a result, it could be used as novel target for anticancer treatments. Because receptor-dependent 4D-QSAR generates conformational ensemble profiles of compounds by molecular dynamics simulations at the binding site of the enzyme, this work describes the synthesis, biological activity evaluation and 4D-QSAR studies of 4,5-dihydro-1,3,4-oxadiazole derivatives targeting cannabinoid receptor. Compared with WIN55,212-2, compound 5 f showed the best antiproliferative activity. The receptor-dependent 4D-QSAR model was generated by multiple linear regression method using QSARINS. Leave-n-out cross-validation and chemical applicability domain were performed to analyse the independent test set and to verify the robustness of the model. The best 4D-QSAR model showed the following statistics: r2 = 0.8487, Q2LOO = 0.7667, Q2LNO = 0.7524, and r2Pred = 0.8358.