A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as ¹H-NMR, ¹³C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01–SM-IMP-13 series have HOMO/LUMO gaps within 4.43–4.69 eV, whereas the compounds of the DA-01–DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24–4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities.

The essential oils (OEs) of the leaves, stems, and spikes of P. marginatum were obtained by hydrodistillation, steam distillation, and simultaneous extraction. The chemical constituents were identified and quantified by GC/MS and GC-FID. The preliminary biological activity was determined by assessing the toxicity of the samples to Artemia salina Leach larvae and calculating the mortality rate and lethal concentration (LC₅₀). The antioxidant activity of the EOs was determined by the DPPH radical scavenging method. Molecular modeling was performed using molecular docking and molecular dynamics, with acetylcholinesterase being the molecular target. The OES yields ranged from 1.49% to 1.83%. The EOs and aromatic constituents of P. marginatum are characterized by the high contents of (E)-isoosmorhizole (19.4–32.9%), 2-methoxy-4,5-methylenedioxypropiophenone (9.0–19.9%), isoosmorhizole (1.6–24.5%), and 2-methoxy-4,5-methylenedioxypropiophenone isomer (1.6–14.3%). The antioxidant potential was significant in the OE of the leaves and stems of P. marginatum extracted by SD in November (84.9 ± 4.0 mg TE·mL⁻¹) and the OEs of the leaves extracted by HD in March (126.8 ± 12.3 mg TE·mL⁻¹). Regarding the preliminary toxicity, the OEs of Pm-SD-L-St-Nov and Pm-HD-L-St-Nov had mortality higher than 80% in concentrations of 25 µg·mL⁻¹. This in silico study on essential oils elucidated the potential mechanism of interaction of the main compounds, which may serve as a basis for advances in this line of research.

Novel multifunctional medication candidates are needed to treat Alzheimer’s disease (AD), a neurodegenerative illness with few treatments. A nitrogen-containing heterocycle, piperidine, is a popular medicinal chemistry scaffold with broad therapeutic potential. We synthesized a series of novel piperidin-1-yl-phenyl-acetamide derivatives (AS-1 to AS-5) by reacting piperidine with 4-chloroaniline and characterizing them by IR, 1 H NMR, 13 C NMR, and mass spectrometry. All compounds meet Lipinski’s rule of five for drug-likeness and oral bioavailability. AutoDockVina molecular docking demonstrated that compounds AS-5 and AS-2 bind acetylcholinesterase (AChE) with affinities comparable to or higher than donepezil, suggesting they may inhibit AChE. AS-5 was the most potent free radical scavenger in DPPH and FRAP studies. Further behavioral evaluation utilizing Y-maze and Morris water maze tests showed that AS-5 was more effective against Alzheimer’s than AS-1. Piperidin-1-yl-phenyl-acetamide derivatives, particularly the 2,5-dimethyl-substituted counterpart (AS-5), have multifunctional properties due to acetylcholinesterase inhibition and antioxidant activity. These findings suggest AS-5 as a lead chemical for optimizing and developing Alzheimer’s disease treatments. The piperidin-1-yl-phenyl-acetamide derivative (AS-5)’s significant acetylcholinesterase inhibition, robust antioxidant action, and in vivo cognitive enhancement comparable to Donepezil make it important. Structure–activity relationship insight highlights the 2,5-dimethyl substitution as a significant driver of increased anti-Alzheimer action, providing a target for next-generation drug design.