Design, synthesis, structural, in silico, and in vitro exploration of structurally modified hydrazones of piperidin-4-one with acetyl & ester moieties

•Structurally modified hydrazones of piperidin-4-one with bioactive chloroacetyl and ester.•Characterization through IR, 1H NMR, 13C NMR, ESI–MS, and SC-XRD.•X-ray analysis revealed the distorted boat conformation of the heterocyclic ring.•Electronic properties and crystal packing were investigated using DFT and Hirshfeld surface analysis.•Biological evaluation carried out using in-silico and In-vitro anticancer studies. The accessibility and bioavailability of medicinally important molecules like piperidones can be improvised by specific structural modifications and such modifications can be effected by acetylation & esterification of core moiety, as it changes physicochemical properties. Synthesis of hydrazinecarboxylate derivatives of 1-(2-chloroacetyl)-3-methyl-2,6-diphenylpiperidin-4-ones (3a-i) which are structural hybrids of hydrazone of piperidone with acetyl and carboxylate templates is being reported in this paper. The synthesized compounds were structurally characterized by IR, 1H & 13C NMR, mass (3a-d, 3f) spectral techniques, and single crystal X-ray diffraction study (3b and 3d). For compound 3b, 2D NMR (HSQC & HMBC) was recorded for unambiguous assignments of chemical shifts. In addition to the SC-XRD for compounds 3b and 3d, the DFT study revealed the distorted boat conformation of the piperidone ring having E – configuration about the hydrazone moiety in both molecules. Hirshfeld surface analysis on 3b and 3d, exposed the H…H interaction in both the molecules supports their crystal stability to the maximum extent (≥ 53 %) while other interactions viz., O…H, Cl…H, C…H also contribute to the crystal stabilization. In silico bio-study for (3a-i) was done by AutoDock4 with human estrogen receptor (3ERT) protein and found the docking scores ranging from − 7.18 to − 8.64 kcal/mol. The compound 3d identified to possess pronounced biological potential towards the tested protein through the molecular docking studies, was subjected to in vitro (MTT) assay against MCF-7 cell line to explore its anticancer potential. [Display omitted]