Design, synthesis, and evaluation of benzhydrylpiperazine-based novel dual COX-2/5-LOX inhibitors with anti-inflammatory and anti-cancer activity.

Piperazine derivatives were screened using the ChEMBL database, paving the way for the design, synthesis, and evaluation of a novel series of dual COX-2/5-LOX inhibitors and identifying their role in mitigating cancer cell proliferation. Compound 9d with 4-Cl substitution at the terminal phenyl ring showed promising inhibition of COX-2 (IC = 0.25 ± 0.

Lead optimization based design, synthesis, and pharmacological evaluation of quinazoline derivatives as multi-targeting agents for Alzheimer's disease treatment.

The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and β-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier.

Structure-Guided Design, Synthesis, and Biological Evaluation of Peripheral Anionic Site Selective and Brain Permeable Novel Oxadiazole-Piperazine Conjugates against Alzheimer's Disease with Antioxidant Potential.

Alzheimer's disease (AD) is a multifactorial and emerging neurological disorder, which has invoked researchers to develop multitargeted ligands. Herein, hybrid conjugates of 5-phenyl-1,3,4-oxadiazole and piperazines were rationally designed, synthesized, and pharmacologically evaluated against hAChE, hBChE, and hBACE-1 enzymes for the management of AD. Among the series, compound comprising pyridyl substitution at terminal nitrogen of piperazine contemplated as a paramount lead compound (hAChE, IC = 0.

Identifying inflammation-related targets of natural lactones using network pharmacology, molecular modeling and approaches.

Natural lactones have been used in traditional and folklore medicine for centuries owing to their anti-inflammatory properties. The study uses a multifaceted approach to identify lead anti-inflammatory lactones from the SISTEMATX natural products database. The study analyzed the natural lactone database, revealing 18 lactones linked to inflammation targets.

Design, Synthesis, and Biological Investigation of Quinazoline Derivatives as Multitargeting Therapeutics in Alzheimer's Disease Therapy.

An efficient and promising method of treating complex neurodegenerative diseases like Alzheimer's disease (AD) is the multitarget-directed approach. Here in this work, a series of quinazoline derivatives ( to ) were rationally designed, synthesized, and biologically evaluated as multitargeted directed ligands against human cholinesterase (hChE) and human β-secretase (hBACE-1) that exhibit moderate to good inhibitory effects. Compounds , , and from the series demonstrated balanced and significant inhibition against these targets.

Design and development of benzyl piperazine linked 5-phenyl-1,2,4-triazole-3-thione conjugates as potential agents to combat Alzheimer's disease.

Our present work demonstrates the molecular hybridization-assisted design, synthesis, and biological evaluation of 22 benzylpiperazine-linked 1,2,4-triazole compounds (PD1-22) as AD modifying agents. All the compounds were tested for their in vitro hChEs, hBACE-1, and Aβ-aggregation inhibition properties. Among them, compound PD-08 and PD-22 demonstrated good hChE and hBACE-1 inhibition as compared to standards donepezil and rivastigmine.

Development and Evaluation of Some Molecular Hybrids of -(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer's Disease.

A series of some novel compounds () were designed following a molecular hybridization approach, synthesized, and biologically tested for hAChE, hBChE, hBACE-1, and Aβ aggregation inhibition potential to improve cognition and memory functions associated with Alzheimer's disease. Compounds and have shown multifunctional inhibitory profiles against hAChE, hBChE, and hBACE-1 enzymes Compounds and have also shown anti-Aβ aggregation potential in self- and acetylcholinesterase (AChE)-induced thioflavin T assay. Both compounds have shown a significant propidium iodide (PI) displacement from the cholinesterase-peripheral active site (ChE-PAS) region with excellent blood-brain barrier (BBB) permeability and devoid of neurotoxic liabilities.

Novel 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives as dual COX-2/5-LOX inhibitors devoid of cardiotoxicity.

A novel series of 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives were designed, synthesized, and screened for their inhibitory potential against COX-2 and 5-LOX enzymes. The compounds from the series have shown moderate to excellent inhibitory potential against both targets. Compound 6k showed the inhibitions against COX-2 (IC = 0.

The molecular mechanism, targets, and novel molecules in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological illness that causes dementia mainly in the elderly. The challenging obstacles related to AD has freaked global healthcare system to encourage scientists in developing novel therapeutic startegies to overcome with the fatal disease. The current treatment therapy of AD provides only symptomatic relief and to some extent disease-modifying effects.

Design, synthesis, and biological evaluation of ferulic acid based 1,3,4-oxadiazole hybrids as multifunctional therapeutics for the treatment of Alzheimer's disease.

Thirty ferulic acid-based 1,3,4-oxadiazole molecular hybrids were designed, synthesized, and screened them for multifunctional inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and beta-secretase-1 (BACE-1). Compound 6j was the most potent inhibitor of AChE (IC = 0.068 µM).