Quinazolinone-Hydrazine Cyanoacetamide Hybrids as Potent Multitarget-Directed Druggable Therapeutics against Alzheimer's Disease: Design, Synthesis, and Biochemical, In Silico, and Mechanistic Analyses.

The discovery of effective multitarget-directed ligands (MTDLs) against multifactorial Alzheimer's disease (AD) remnants has been focused in an incessant drug discovery pursuit. In this perception, the current study explores the rational design, synthesis, and evaluation of 26 quinazolinone-hydrazine cyanoacetamide hybrids , , and as MTDLs against AD. These new compounds were synthesized in four-step processes using simple phthalimide as the starting material without any major workup procedures and were characterized by different spectroscopic techniques.

Development of quinazolinone and vanillin acrylamide hybrids as multi-target directed ligands against Alzheimer's disease and mechanistic insights into their binding with acetylcholinesterase.

In view of Multi-Target Directed Ligand (MTDL) approach in treating Alzheimer's Disease (AD), a series of novel quinazolinone and vanillin cyanoacetamide based acrylamide derivatives () were designed, synthesized, and assessed for their activity against a panel of selected AD targets including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), amyloid β protein (Aβ), and also 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and neuroprotective activities. Five of the target analogs , , , and showed elevated AChE inhibitory activity with IC values of 1.058 ± 0.

Synthesis and anti-Alzheimer potential of novel α-amino phosphonate derivatives and probing their molecular interaction mechanism with acetylcholinesterase.

Pleiotropic interference may be a prerequisite for the efficient limitation of the progression of multi-factorial diseases such as Alzheimer's disease (AD). Concept of designing the single chemical entity acting on two or more targets of interest has potential advantage in AD therapy. In line with this, rational design and synthesis of frame work of hybrids bearing 2,3-disubstituted quinazolinone, vanillin and α-amino phosphonate scaffolds (5a─v) were carried out.

Synthesis and assessment of anticholinesterase and antioxidant properties of triazineamide derivatives.

Cholinesterase inhibitors and radical scavengers have been recognized as powerful symptomatic anti-Alzheimer's disease agents. Hence, the present study aimed to develop new triazineamides as potent anticholinesterase and antioxidant agents. Triazineamide () derivatives were synthesized using cyanuric chloride via nucleophilic substitution followed by condensation.

New Flavone-Cyanoacetamide Hybrids with a Combination of Cholinergic, Antioxidant, Modulation of β-Amyloid Aggregation, and Neuroprotection Properties as Innovative Multifunctional Therapeutic Candidates for Alzheimer's Disease and Unraveling Their Mechanism of Action with Acetylcholinesterase.

In line with the modern multi-target-directed ligand paradigm of Alzheimer's disease (AD), a series of 19 compounds composed of flavone and cyanoacetamide groups have been synthesized and evaluated as multifunctional agents against AD. Biological evaluation demonstrated that compounds 7j, 7n, 7o, 7r, and 7s exhibited excellent inhibitory potency (AChE, IC of 0.271 ± 0.

Screening of Three Indian Medicinal Plants for Their Phytochemicals, Anticholinesterase, Antiglucosidase, Antioxidant, and Neuroprotective Effects.

Cooccurrence of Diabetes Mellitus and Alzheimer's disease in elder people prompts scientists to develop multitarget agents that combat causes and symptoms of both diseases simultaneously. In line with this modern paradigm and as a follow-up to our previous studies, the present study is designed to investigate the crude methanolic extracts and subsequent CHCl, -BuOH, and HO fractions of , and for their inhibitory activities towards specific targets involved in AD and DM, namely, acetylcholinesterase, butyrylcholinesterase, and -glucosidase (-Glc). The methanolic extract and its derived chloroform fractions exhibited remarkable inhibitory capacities with IC values being found at the g/mL level.

Synthesis, Biological Evaluation, and Molecular Docking of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease.

Alzheimer's disease onset and progression are associated with the dysregulation of multiple and complex physiological processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene analogs (4a-q) were synthesized and evaluated for their multitarget-directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, and amyloid-β peptide (Aβ) specific targets for Alzheimer's disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nm concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity.

Flavonoids and ent-labdane diterpenoids from Andrographis paniculata and their antiplatelet aggregatory and vasorelaxing effects.

Two new flavones, designated as andropaniculosin A (1) and andropaniculoside A (2), and 30 known compounds were isolated as a result of detailed chemical examination on the whole plants of Andrographis paniculata. Their structures have been elucidated mainly by 1D and 2D NMR, and MS spectroscopic methods. Among them, four flavonoids showed potent inhibition of collagen, arachidonic acid, thrombin, and platelet activation factor induced platelet aggregation.

Isolation and identification of antiplatelet aggregatory principles from the leaves of Piper lolot.

The methanolic extract of Piper lolot, having shown potent inhibitory activity on platelet aggregation induced by arachidonic acid (AA) and platelet activating factor (PAF), was subjected to activity-guided isolation to yield twelve new amide alkaloids, piperlotine A-L (1-12), along with twenty-nine known compounds. Their structures were elucidated on the basis of spectroscopic analysis. The isolated compounds were tested for their inhibitory activity on the rabbit platelet aggregation.

Anthraquinones from Ophiorrhiza hayatana OHWI.

Three new naturally occurring anthraquinones, ophiohayatone-A (1), -B (2), and -C (3), together with four known anthraquinones, were isolated from Ophiorrhiza hayatana OHWI (Rubiaceae). Structures of these new compounds were established by spectral methods.

Constituents of leaves of Phellodendron japonicum MAXIM. and their antioxidant activity.

Three new flavonoid derivatives, 6'''-O-acetyl amurensin (1), 6'''-O-acetyl phellamurin (3) and (2R)-phellodensin-F (5), together with thirty known compounds have been isolated from the leaves of Phellodendron japonicum MAXIM. Their structures were established by means of spectroscopic analysis, including extensive 2D NMR and Mass spectra. The known compounds were identified by comparison with published physical and spectral data.

New neolignans from Spiraea formosana.

Phytochemical investigation on the ethanol extract from the stems of Spiraea formosana has resulted in the isolation of four new neolignans, named spiraformin-A, -B, -C and -D (1-4), together with thirty five known compounds. Their structures were established primarily on the basis of 1D and 2D NMR spectral and chemical transformation methods.

The alkaloids and other constituents from the root and stem of Aristolochia elegans.

Two new aristolactams, aristolactam E (1) and aristolactam-AIIIa-6-O-beta-D-glucoside (2), three novel benzoyl benzyltetrahydroisoquinoline ether N-oxide alkaloids, aristoquinoline A (3), aristoquinoline B (4), and aristoquinoline C (5), and a new biphenyl ether, aristogin F (6), together with 62 known compounds have been isolated from the root and stem of Aristolochia elegans Mast. The structures of the new natural products were established on the basis of spectral evidence. Some of the isolated compounds were examined for their antioxidative and antityrosinase activities.

Flavonoids from Andrographis viscosula.

Phytochemical investigation of the whole plant of Andrographis viscosula has led to the isolation of three new 2'-oxygenated flavonoids, (2R)-5-hydroxy-7,2',3'-trimethoxyflavanone (1), 7,2',5'-trimethoxyflavone (2), 5,7,2',3'-tetramethoxyflavone (3), and eight known flavones, 5,7,2'-trimethoxyflavone (4), 5,7,2',4',5'-pentamethoxyflavone (5), echioidinin (6), 5,2',6'-trihydroxy-7-methoxyflavone (7), 5-hydroxy-7,2'-dimethoxyflavone (8), echioidin (9), echioidinin 5-O-glucoside (10), and 5,2',6'-trihydroxy-7-methoxyflavone 2'-O-glucoside (11). The structures of 1-11 were elucidated by physical and spectral methods, including extensive 2D NMR studies. The presence of 2'-oxygenated flavonoids is apparently restricted to Andrographis species in Acanthaceae.

Cytotoxic anthraquinones from the stems of Rubia wallichiana Decne.

From the stems of Rubia wallichiana DECNE, thirty-four structurally related compounds were isolated and identified. Three of them, namely rubiawallin-A (1), -B (2), and -C (3), constitute the first report of their occurrence from the natural source. Their structures were determined by comprehensive analyses of their 1D and 2D NMR, and electron impact (EI) mass spectral data.

Chemical constituents of Taraxacum formosanum.

Three new compounds, taraxacine-A (1), taraxacine-B (2) and taraxafolin (3) together with twenty-five known compounds, which include two beta-carboline alkaloids, two indole alkaloids, two chlorophylls, two flavonoids, one coumarin, two triterpenoids, one monoterpenoid, one ionone, four steroids and eight benzenoids, were isolated and characterized from the fresh aerial parts of Taraxacum formosanum. Structures of new compounds were determined by spectral analysis.