Design and synthesis of novel hydrazinyl thiazoles from biomass derived furfurals: Their molecular docking, anti-cancer, anti-oxidant, and anti-bacterial study

This report presents an application of simple and convenient grindstone chemistry to construct a library of pharmaceutically valuable hydrazinyl thiazole moieties using biomass-derived furfurals as key synthons. Significantly, the current green process avoids the use of catalysts and solvents for the desired conversion, achieving good to excellent product yields in a short reaction time. The synthesized compounds were evaluated for their anti-cancer activity against the human breast cancer cell line (MCF-7) using an in vitro MTT assay, which revealed significant antiproliferative activity of compounds 4d and 4e, with IC₅₀ values of 41.06±0.06 and 38.39±0.90 μg/mL, respectively.

Further, the in vitro antibacterial activity of the newly synthesized thiazole derivatives and reference drugs was assessed against both gram-negative bacteria, including Escherichia coli, and gram-positive bacteria such as Bacillus subtilis. The current research demonstrates that compounds 4d and 4e exhibit significantly enhanced antibacterial efficacy against pathogenic bacteria, with MIC values >25 μg/mL and >6.25 μg/mL for E. coli, and >25 μg/mL for Bacillus subtilis for both compounds. The DPPH assay revealed that compounds 4a, 4d, and 4e were the most significant, displaying comparatively higher IC₅₀ values of 41.58±1.28, 42.36±0.45 and 42.31±0.73 μg/mL respectively.

Furthermore, the synthesized compounds were investigated through molecular docking studies, which were consistent with the in vitro results. The findings were further supported by a structure-activity relationship (SAR) study.