Targeted synthesis via the structure-activity relationship: Biological evaluation of new 1,2,3-triazoles monoterpene as antitumor agents

Abstract

• A novel series of thiazolidinone based 1,2,3-triazole derivatives were designed, synthesized, and evaluated for their cytotoxic activity. • Anti-proliferative activity was assessed against HT-1080, A-549, MCF-7 and MDA-MB-231 cells lines. • Hybrid compounds 14b and 14d showed important inhibitory activity against HT-1080 and A-549 cancer cell lines with an IC 50 value of 18 μM. • Binding modes of all compounds were identified via molecular docking. • Compounds 14b and 14d had higher affinity for Bcl-2 as compared to other compounds. A novel series of thiazolidinone based 1,2,3-triazole derivatives were designed, synthesized, and evaluated for their cytotoxic activity against four human cancer cell lines, including fibrosarcoma (HT-1080), lung carcinoma (A-549), and breast carcinoma (MCF-7 and MDA-MB-231). NMR ( 1 H and 13 C) and HRMS established the newly synthesized compounds' structural identification and molecular weight. Most synthesized compounds displayed moderate cytotoxic activity, with IC 50 values from 20 to 40 μM. Furthermore, hybrid compounds 14b and 14d showed important inhibitory activity against HT-1080 and A-549 cancer cell lines with an IC 50 value of 18 μM. Molecular docking analyses also confirmed a higher binding affinity of compounds 14a-e , as compared to Doxorubicin (control), towards Bcl-2 protein. In particular, compounds 14b and 14d had higher affinity for Bcl-2 as compared to other compounds.