Molecular docking studies and synthesis of a new class of chroman-4-one fused 1,3,4-thiadiazole derivatives and evaluation for their anticancer potential

gamma-Secretase inhibitors (GSIs) are repurposed as cancer therapeutics based on the promising inhibition of NOTCH1 signalling pathway in various cancers. GSIs are a class of small-molecule compounds that target the Notch pathway and have been tested to treat various types of cancers in preclinical and clinical trials. Although GSIs elicit a response in some tumours as single agents and sensitize to cytotoxic and targeted therapies, they have not yet been approved for cancer therapy. A new series of chroman-4-one fused 1,3,4-thiadiazole derivatives has been synthesized with the help of different aromatic benzaldehydes, and the final compounds were characterized by FT-IR and (HNMR)-H-1. Chroman-4-one fused 1,3,4-thiadiazole derivatives were synthesized by the reaction of Schiff base derivatives with chroman-4-one fused 1,3,4-thiadiazole. All the synthesized compounds were screened for their anticancer activity. These compounds were evaluated for their anticancer activity against MDA-MB-231, MCF-7, and Vero cancer cell lines. Four of the compounds possessed good to moderate anticancer activity. Four of the synthesized compounds, i.e. 3a, 3c, 3i, and 3e, were found to possess maximum growth inhibition. In conclusion, the designed chromanone-1,3,4-thiadiazole scaffold is an interesting anticancer pharmacophore and considered as novel lead scaffold for any future optimization.