Synthesis, characterization, cytotoxicity evaluation and molecular docking study of new bis-chalcone, fused-pyrimidine and fused-pyrazoline derivatives

Abstract

Chemotherapeutic drug resistance and high-risk side effects are common limitations in cancer treatment. Thus, the continuous development of new drugs that target only the cancer cell without affecting the normal cells is needed. The simple structure of the chalcone and the ease of its synthesis showed promising functions. Such compounds have been reported to exhibit diverse pharmacological activities, particularly anticancer. This study involves the design of chalcones 1 and 2 which have been synthesized via Claisen-Schmidt condensation. Further cyclo-condensation reactions of these chalcone compounds has formed five pyrazoline and three pyrimidine derivatives. All the desired derivatives are characterised by FT-IR, ¹H-NMR, and ¹³C-NMR. These derivatives are tested for cytotoxicity against breast cancer cell lines (MCF-7 and MD-MB-231) and normal breast cell lines (MCF-10A). The results emphasized that pyrazoline compounds 1Aii and 1Aiii are showing the minimum inhibition against MCF-7 with the IC₅₀ values of56.73±3.3 µM and 37.74±1.32 µM, respectively, after 24 h of exposure, which are comparable to Tamoxifen, as reference anticancer drug (IC₅₀ = 42.66±2.19 µM).