Synthesis, molecular docking, anti-cancer activity, and in-silico ADME analysis of novel spiroacenaphthylene pyrrolizidine derivatives

A short and efficient multicomponent sequence for synthesizing spiroacenaphthylene pyrrolizidine analogs 5a-s via 1,3-dipolar cycloaddition reaction of azomethine ylide with chalcones 4a-s without any catalyst. Synthesized compounds 5a-s were characterized by spectral data and single crystal X-ray diffraction study. In-vitro anti-proliferative activity of compounds 5a-s against K562-leukemia showed that compounds 5e, 5i, 5l, 5m and 5o have an IC 50 value of 54.07, 47.48, 50.57, 53.85 and 49.57 mu g/ml respectively and exhibited H-bonding with LYS 875 in the molecular docking studies against the 2J5F protein and showed favourable in-silico ADME properties. Compound 5o showed favourable i n-vitro anti-proliferative activity against K562-leukemic cell line and favourable in-silico ADME properties. It can serve as a template to develop further as a lead molecule and act as a tyrosine kinase inhibitor.(c) 2022 Elsevier B.V. All rights reserved.