Design, spectroscopic characterization, in silico and in vitro cytotoxic activity assessment of newly synthesized thymol Schiff base derivatives

Cancer is a global public health problem affecting millions of people every year. New anticancer drug candidates are needed to overcome the resistance to drugs used in the treatment of various types of cancer. In this study, two new series of benzenesulfonate-based thymol derivatives (14–19 and 20–25) were synthesized for the first time as promising chemotherapeutic agents and characterized using FT-IR, 1D NMR (1H- and 13C-NMR, APT, DEPT 135), 2D NMR (HETCOR and HMBC), and elemental analysis (CHNS). Antiproliferative activity of the molecules was determined against cancer cell lines, namely, the human lung adenocarcinoma cell line (A549) and the colorectal adenocarcinoma cell line (DLD-1), using MTT method for both 48 and 72 h. Compounds (14–25) showed cytotoxic activities against A549 with IC50 values ranging from 9.98 to 81.83 μM, respectively, compared to cisplatin (6.65 μM). These compounds exhibited antiproliferative activities against DLD-1 cancer cells at concentrations ranging from 4.29 to 53.62 μM, respectively, compared to cisplatin (9.91 μM). Especially, compound 16 displayed significant cytotoxicity on A549 and DLD-1 cancer cells with IC50 values of 9.98 and 10.75 μM, respectively. Finally, molecular docking studies were performed with Bcl-2, VEGFR-2, EGFR, and HER2 targets using the Schrödinger 2021-2 Maestro Glide program. The binding energy values and binding interactions of compounds 16 and 22 were determined to be the result of their interactions with these targets. Schrödinger 2021-2 Qikprop wizard drug similarity ratios and ADME prediction of all compounds 14–25 were also calculated. © 2024 Informa UK Limited, trading as Taylor & Francis Group.