Synthesis, X-ray, Hirshfeld combined with DFT, anticancer effects with molecular docking confirmation of (E)-4-cyanobenzaldehyde oxime and (Z)–N-methyl-C-4-substituted phenyl aldonitrones

Abstract

(E)-4-cyanobenzaldehyde oxime 1 and (Z)–N-methyl-C-4-substituted phenyl aldonitrones 2 and 3 were synthesised and fully characterised. With the help of Hirshfeld calculations, the molecular packing of 1 is found to be controlled by short N…H contacts (28.3%) in addition to the aromatic π-π stacking where the%C…C interactions is calculated to be 9.7%. In this case, the second most abundant interaction is H…H contact (28.1%). For 2, the N…H (24.4%) and O…H (13.8%) contacts are the most important while the most abundant interaction is H…H contacts (36.0%). DFT calculations were utilised to explore the structural and electronic parameters of both compounds at their optimised geometries which were found in good agreement with the X-ray structures. The structure of 2 (6.9829 Debye) is more polar than 1 (4.5282 Debye). The compounds 1–3 reduced the growth of MCF-7 and T47D. Compound 1 which has the lowest IC50 values against the MCF-7 and T47D cell lines, is thought to be the most promising applicant as an anticancer drug. The in-silico combination of compounds 1–3 with proliferative proteins PIK3 and CDK5, autophagic proteins mTOR and beclin, antiapoptotic proteins BCL2, and apoptotic proteins caspase 3 was examined. Compound 3 binds to PIK3, CDK5, mTOR, Beclin, BCL2 and caspase 3, and displays higher free energy bindings of −5.12, −5.45, −4.923, −5.72, −4.45 and −4.73 kcal/mol, which suggested that these proteins had the strongest inhibitory or enhanced effects. The findings show that compound 3 was the most well-docked chemical with the greatest IC50. Compound 3 impacted the autophagy, apoptotic and mitotic proteins of cell growth.