Polyhydroquinoline (PHQ) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, twenty-five (3–27) new Schiff’s base derivatives of polyhydroquinoline hydrazide were synthesized in excellent to good yields by a multi-component reaction. The structures of the synthesized products (1–27) were deduced with the help of spectroscopic techniques, such as ¹H-, ¹³C -NMR, and HR-ESI-MS. The synthesized products (1–27) were tested for their antibacterial and in vitro calcium -channel-blocking (CCB) potentials using the agar-well diffusion method, and isolated rat aortic ring preparations, respectively. Among the series, sixteen compounds were found to inhibit the growth of Escherichia coli and Enterococcus faecalis. Among them, compound 17 was observed to be the most potent one at a dose 2 µg/mL, with an 18 mm zone of inhibition against both bacteria when it was compared with the standard drug amoxicillin. Eight compounds showed CCB activity of variable potency; in particular, compound 27 was more potent, with an EC₅₀ value of 0.7 (0.3–1.1) µg/mL, indicating their CCB effect.

This study reports the isolation of three new C₂₀ diterpenoid alkaloids, Chitralinine A–C (1–3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1–3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC₅₀ value of 11.64 ± 0.08 μM against AChE, and 24.31 ± 0.33 μM against BChE, respectively. The molecular docking reflected a binding free energy of −16.400 K Cal-mol⁻¹ for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer’s disease.

In this study, bis ‐Schiff base derivatives bearing 4‐hydroxyacetophenone were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities. In the series, compound ( 2i ) was identified as the most promising inhibitor of AChE (IC ₅₀ = 14.82 ± 0.09 µM) and BuChE (IC ₅₀ = 27.91 ± 0.16 µM) enzymes surpassing the standard drug galantamine, while the remaining derivatives showed good to moderate inhibition. Structure–activity relationship (SAR) study exposed those methoxy groups attached to the benzene ring significantly improved enzyme inhibition, while electron‐withdrawing groups led to condensed the activities. Molecular docking simulations against AChE and BuChE revealed distinct binding modes, with 2i forming critical bonds with catalytic residues. Quantum chemical analysis established strong correlations between electrophilicity index ( ω = 4.712 eV for 2i ), HOMO–LUMO gap (4.287 eV), and experimental inhibition. Quantum Theory of Atoms in Molecules (QTAIM) analysis supporting optimal electron density distribution and favorable non‐covalent interaction patterns. Comprehensive in silico ADMET profiling predicted excellent pharmacokinetic properties for all derivatives, with 96%–100% human oral absorption, moderate blood–brain barrier (BBB) penetration for 2i , and low cardiac toxicity risk. The integrated computational‐experimental approach provides supportive evidence for rational design of next‐generation cholinesterase inhibitors with optimized efficacy and safety profiles.