Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• (ROSs) [28]. Crocins can inhibit the activity of acetylcholinesterase and increase the acetylcholine concentration, thus improving the learning and memory ability of the brain [29]. Moreover, crocins prevent the abnormal aggregation of amyloid β-protein (Aβ), microtubule-associated protein tau, and α

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• ]. Previous studies have shown that 2-(2-phenylethyl)chromones and sesquiterpenes are the characteristic and main bioactive components of agarwood [5][6]. Various bioactivities, including neuroactive [4], gastrointestinal modulation [7], cytotoxicity [8], antibacterial [9], antifungal, acetylcholinesterase

• studies, the components from A. sinensis possess various attractive bioactivities, such as anti-inflammatory, anticancer, antirenal fibrosis, and acetylcholinesterase inhibitory effects, which motivate us to assume that compounds with similar skeletons may have the same bioactivities. Therefore, the new

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• synthesis of (±)-physovenine and (±)-physostigmine alkyl analogues exhibiting inhibitory activity against acetylcholinesterase and butyrylcholinesterase [30][78][79][80][81][82][83][84]. Subsequently, we expanded the scope of this protocol to include a benzamide derived acrylamide 1r. The expected six

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• UMB32 and UMB136 [33][34]. Zhang developed 4-aminoquinolines for the synthesis of fluorinated analogues of acetylcholinesterase (AChE) inhibitors [35] in cascade reactions, such as one-step syntheses of quinolines. Quinolin-4-ols involving histone acetyltransferases (HAT) inhibitors [36][37], as well as

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase. Keywords: acetylcholinesterase

• brain of patients suffering with the Parkinson’s and the Alzheimer’s disease, respectively. Therefore, research is focused on the discovery of new drugs protecting acetylcholine and dopamine levels via inhibition of acetylcholinesterase (AChE) and monoamine oxidase (MAO). A promising source of such

• until recently. In 2019 a study of Naidoo et al. [20] reported naturally occurring karrikins as compounds with moderate inhibitory activity against both types of monoamine oxidases (MAO-A and MAO-B) and acetylcholinesterase, while the sulfur bioiostere 3-methyl-2H-thiopyrano[3,4-b]furan-2-one (8) [21

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• acetylcholinesterase inhibitors [11][12][13], being LSPN223 the most potent compound (Figure 2). Furthermore, coumarin derivatives have been used as fluorescent probes, laser dyes, fluorescent chemosensors, light absorbers for solar cells, optical brighteners, and organic light emitting diodes (OLEDs) [14][15]. From a

• electron-donating and electron-withdrawing substituents. Additionally, the products were evaluated as acetylcholinesterase (AChE) inhibitors and compound 93d showed a promising activity. Gurubrahaman et al. developed a method for the synthesis of (Z)-2-methylenepyrans 96 through a conjugated addition of 4

• acetylcholinesterase by coumarin derivatives. Michael addition of 4-hydroxycoumarins 1 to α,β‐unsaturated enones 2. Organocatalytic conjugate addition of 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed by an IMCR. Synthesis of 3,4-dihydrocoumarin derivatives 10 through decarboxylative and dearomatizative

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• difluoroalkane moiety. We show that this fluorinated analog of piperine has superior physicochemical properties, and it also has higher potency and selectivity towards one particular drug target, acetylcholinesterase. This work highlights the potential usefulness of the threo-difluoroalkane motif as a surrogate

• carried out, and these studies have led to a diverse array of biological activities being claimed for this compound [4][5][6][7][8][9]. For example, 1 is reported to exhibit inhibitory activity towards both acetylcholinesterase (AChE) and β-secretase (BACE-1), which suggests that 1 could hold promise as a

• described for 1 led to no detectable decomposition (Figure 3, Supporting Information File 1). Biological activity and solubility The biological activities of piperine (1) and the analog 2 were compared using two different assays, namely the inhibition of either acetylcholinesterase (AChE) or β-secretase

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• binding sites (Figure 1) [20]. The smallest member of this family, methyl sulfonyl fluoride (MSF), is known as a selective and irreversible inhibitor of acetylcholinesterase (AChE) [21][22]. The sulfonyl fluoride inhibitors NSC 127755 was found for specifically modifying tyrosine-31 of DHFR in chicken

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• 10210, Thailand 10.3762/bjoc.14.231 Abstract A series of 3-amino-6,7-dimethoxycoumarins conjugated with the N-benzylpyridinium moiety through an amide-bond linkage was synthesized and evaluated for their acetylcholinesterase inhibitory activity. A number of the benzylpyridinium derivatives exhibited

• target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme. Keywords: acetylcholinesterase inhibitor; 3-aminocoumarin; N-benzylpyridinium; dual binding site

• remains incurable; most of the existing treatments only delay the onset or further advancement of AD. Among the current hypotheses for the treatment of AD, inhibition of acetylcholinesterase enzyme (AChE), which is responsible for the degradation of the neurotransmitter acetylcholine (ACh), is the most

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -indanone derivatives 66 were obtained in 13–86% yields (Scheme 22). This method was further applied to the synthesis of biologically active compounds, such as 1-tetralones, 1-benzosuberones and donepezil (a potent acetylcholinesterase inhibitor used in the treatment of Alzheimer’s disease). Halo-1

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• scavengers 1–4 were tested for their ability to prevent the inhibition of acetylcholinesterase by the chemical warfare agent soman (Figure 11). The heterodifunctionalized derivatives 1 and 3 were, this time, the most effective compounds. Preincubation of compounds 1 and 3 with soman for 60 minutes reduced

• methyl parathion (0.5 mM). The final concentrations of compounds 2, 4, 2-iodosobenzoic acid (IBA), imidazole and TRIMEB were 0.25 mM. Ability of compounds 1–4 in preventing the inhibition of acetylcholinesterase by soman (GD). Synthetic pathway to derivatives 2 and 3 (Tr = trityl). Synthesis of compound

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• sector in generating structure and function diverse O-nitrate esters for use as in vivo NO-donors. In this context particular emphasis has been placed on developing O-nitrate esters as biologically active agents that act on acetylcholinesterase (AChE), amyloid-βx-42 (Aβ42) aggregation, cyclooxygenase-II

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• , our group has developed a hybrid drug combining silibinin with tacrine (a potent acetylcholinesterase inhibitor for treatment of Alzheimer’s disease), which shows neuro- and hepatoprotective effects exceeding the cytoprotective effects of silibinin and effectively counteracts tacrine’s dose-dependent

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• ], acetylcholinesterase inhibitors [3], and antibacterial agents [4][5]. Due to the strong inhibitory activity of 1,2,4-thiadiazoles against kinase-3β, they can be used for treatment of diabetes (type II) and chronic inflammation [6][7]. Therefore, their synthesis is a field of continuing interest for many chemists [1][8

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• anti-oxidant, and acetylcholinesterase (AChE), α-glucosidase, and topoisomerase IIα inhibitory activities at a concentration of 50 μg/mL. Antimicrobial activities against a variety of plant pathogenic bacteria (Xanthomonas oryzae pv. oryzae Swings, Xanthomonas oryzae pv. oryzicola Swings, Acidovorax

• biosynthetically derived from hypothetical intermediate pimarane compound 2, the hemiketal lactone ring-opening product of aspergiloid E. In biological tests, 1 showed no cytotoxic, antimicrobial, anti-oxidant, acetylcholinesterase (AChE), α-glucosidase, and topoisomerase IIα inhibitory activities. In order to

• graminearum Schw., Fusarium coeruleum Sacc., Botrytis cinerea Pers., and Fusarium oxysporum f. sp. cubense race 4), and Candida albicans (ATCC 10231), and the antioxidant, acetylcholinesterase (AChE) , α-glucosidase, and topoisomerase IIα inhibitory activities were performed in accordance with the primary

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• ) [24] increased cell viability by 17.3% and 22.4% in H2O2 and Aβ25–35 model, respectively. Compounds rac-7a,b and rac-5 did not show acetylcholinesterase inhibitory effect. Conclusion Regioselective domino Knoevenagel–[1,5]-hydride shift cyclization reactions of a 4-aryl-2-phenyl-1,4-benzoxazepine

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• allowed the authors to perform these reactions with ten times smaller volume of the solvent than that employed in the reactions carried out under conventional heating conditions. Compound 83b showed promising activity against acetylcholinesterase at a concentration of 100 µmol/L. 6. The Hantzsch reaction

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• ; quinazoline alkaloid; Introduction Quinazoline alkaloids are a class of naturally occurring compounds with a range of medicinal properties and have been indicated for use as bronchodilators, vasodilators, anti-inflammatory agents and acetylcholinesterase inhibitors [1][2][3][4][5]. Many of the plants these

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• substituents with an aldoxime or a ketoxime moiety along the narrow opening of the β-cyclodextrin cavity was synthesized, and the ability of these compounds to reduce the inhibitory effect of the neurotoxic organophosphonate cyclosarin on its key target, acetylcholinesterase, was assessed in vitro. All

• the nine compounds investigated, one exhibited remarkable activity, completely preventing acetylcholinesterase inhibition by the (−)-enantiomer of cyclosarin within seconds under the conditions of the assay. Thus, these investigations demonstrate that decoration of cyclodextrins with appropriate

• substituents represents a promising approach for the development of scavengers able to detoxify highly toxic nerve agents. Keywords: acetylcholinesterase; cyclodextrins; cyclosarin; neurotoxic organophosphonates; oximes; Introduction Cyclodextrins, cyclic oligosaccharides composed of α-1,4-linked D-glucose