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Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC 50 value of 0.49 μM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE 2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aβ 42 aggregation. Moreover, the selected nuclide [ 18 F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The natural product paeonol is a rich and sustainable natural bioresource, and its derivatives have various unique biological efficacy. As is well known, Schiff bases are a class of organic compounds with a wide range of biological activities, including anti-fungal, insecticidal, anti-viral, and nematicidal., Results: To discover biorational natural product-based pesticides, nine intermediates (2-10), 12 sulfonylhydrazones (11a-11c, 12a-12c, 13a-13c, and 14a-14c) and 20 benzylidene hydrazones (18a-18r, 19a, and 20a) were synthesized by structural modification of paeonol, and their structures were characterized by proton nuclear magnetic resonance ( 1 H NMR), carbon-13 ( 13 C) NMR, and high-resolution mass spectrometry (HRMS). The stereochemical configurations of compounds 14a, 18d, and 18r were unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete, anti-fungal, and nematicidal agents against three serious agricultural pests, Phytophthora capsici, Fusarium graminearum, and Heterodera glycines were evaluated. Among all tested compounds: (i) compound 7 exhibited promising anti-oomycete against Phytophthora capsici, with a half maximal effective concentration (EC 50 ) value of 15.81 mg L -1 ; (ii) compounds 2, 7, 10, and 19a displayed promising anti-fungal against F. graminearum, with EC 50 values of 12.22, 14.72, 23.39, and 33.10 mg L -1 , respectively; (iii) ten compounds (12a-12c, 14c, 18g-18j, 18m, and 19a) showed significant nematicidal activity against H. glycines, with median lethal concentration (LC 50 ) values all less than 30.00 mg L -1 . Especially for compound 18g, its LC 50 value is the smallest, at 12.65 mg L -1 ., Conclusion: The research results indicate that introducing nitro groups at the C5 position of paeonol, or introducing halogens at both C5 and C3 positions, can significantly enhance its biological activity against Phytophthora capsici, F. graminearum, and H. glycines. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Pyruvate dehydrogenase kinases (PDHKs), important metabolic and abnormally expressed enzymes in cancer cells, are promising targets for cancer therapy, especially for non-small-cell lung cancer (NSCLC)., Methods: In this study, a new hit, dichloroacetophenone (DAP) analog 9 , was postulated to bind to the PDHK1 allosteric pocket, guided by molecular modeling and kinase biochemical experiments. Based on this binding mode, novel DAP analogs were designed and synthesized to confirm the importance of Phe180, Tyr411, and the hydrophobic core at the bottom of the pocket., Results: This structure-activity relationship (SAR) study led to the discovery of a novel potent hybrid scaffold, dichloroacetophenone biphenylsulfone ether. Dichloroacetophenone biphenylsulfone ether 31 and 32 inhibited PDHK1 with IC 50 values of 86 and 140 nM, respectively., Conclusion: Compound 32 with acceptable in vitro metabolic stability, predicted drug-likeness properties and ADME/T profiles, showed promising therapeutic efficacy in a lung cancer xenograft mouse model., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study., (© 2024 Wu et al.)

Paeonol is a broadly studied natural product due to its many biological activities. Using a methodology previously employed by our research group, 11 derivatives of paeonol were synthesized (seven of them are unpublished compounds), including four ethers and seven benzofurans. Additionally, we determined the crystal structure of one of these ether derivatives (1 a) and of five benzofuran derivatives (2 a, 2 b, 2 c, 2 f and 2 g) by single crystal X-ray diffraction. To continue studying the cytotoxicity of this natural product and its derivatives, all compounds were tested against two cancer cell lines, HCT116 and MCF-7. Compounds 2 b, 2 e, and 2 g were considered active against the colorectal adenocarcinoma cells HCT116 (Growth inhibition >60 %). Compound 2 e showed an IC 50 of 0.2 μM and was selected for further analysis, results reinforce its anticancer potential., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Twenty-five acetophenone/piperazin-2-one (APPA) hybrids were designed and synthesized based on key pharmacophores found in anti-breast cancer drugs Neratinib, Palbociclib, and Olaparib. Compound 1j exhibited good in vitro antiproliferative activity (IC 50  = 6.50 μM) and high selectivity (SI = 9.2 vs HER2-positive breast cancer cells SKBr3; SI = 7.3 vs normal breast cells MCF-10A) against triple negative breast cancer (TNBC) cells MDA-MB-468. In addition, 1j could selectively cause DNA damage, inducing the accumulation of γH2AX and P53 in MDA-MB-468 cells. It also reduced the phosphorylation level of P38 and the expression of HSP70, which further prevented the repair of DNA damage and caused cells S/G 2 -arrest leading to MDA-MB-468 cells death., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: Synthesis of novel bis -Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis -Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

T-LAK-cell-originated protein kinase (TOPK), a novel member of the mitogen-activated protein kinase family, is considered an effective therapeutic target for skin inflammation. In this study, a series ( A - D ) of paeonol derivatives was designed and synthesised using a fragment growing approach, and their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells were tested. Among them, compound B12 yielded the best results (IC 50 = 2.14 μM) with low toxicity (IC 50 > 50 µM). Preliminary mechanistic studies indicated that this compound could inhibit the TOPK-p38/JNK signalling pathway and phosphorylate downstream related proteins. A murine psoriasis-like skin inflammation model was used to determine its therapeutic effect.

Alzheimer's disease (AD) possesses a complex pathogenetic mechanism. Nowadays, multitarget agents are considered to have potential in effectively treating AD via triggering molecules in functionally complementary pathways at the same time. Here, based on the screening (∼1400 compounds) against neuroinflammation, an imidazolylacetophenone oxime ether (IOE) was discovered as a novel hit. In order to obtain SARs, a series of imidazolylacetophenone oxime derivatives were constructed, and their C=N bonds were confirmed as the Z configuration by single crystals. These derivatives exhibited potential multifunctional neuroprotective effects including anti-neuroinflammatory, antioxidative damage, metal-chelating, inhibition of acetylcholinesterase (AChE) properties. Among these derivatives, compound 12i displayed the most potent inhibitory activity against nitric oxide (NO) production with EC 50 value of 0.57 μM 12i can dose-dependently suppress the expression of iNOS and COX-2 but not change the expression of HO-1 protein. Moreover, 12i exhibited evidently neuroprotective effects on H 2 O 2 -induced PC12 cells damage and ferroptosis without cytotoxicity at 10 μM, as well as selectively metal chelating properties via chelating Cu 2+ . In addition, 12i showed a mixed-type inhibitory effect on AChE in vitro. The structure-activity relationships (SARs) analysis indicated that dioxolane groups on benzene ring and rigid oxime ester can improve the activity. Parallel artificial membrane permeation assay (PAMPA) also verified that 12i can overcome the blood-brain barrier (BBB). Overall, this is the first report on imidazolylacetophenone oxime-based multifunctional neuroprotective effects, suggesting that this type of compounds might be novel multifunctional agents against AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

American trypanosomiasis (Chagas disease) caused by the Trypanosoma cruzi parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of T. cruzi , with a half effective concentration of 18.3 µM ± 1.1 and an index of selectivity > 10.9.

Although the administration of combined therapy is efficient to tuberculosis (TB) treatment caused by susceptible Mycobacterium tuberculosis strains, to overcome the multidrug resistance is still a challenge. Some studies have reported evidence about tetrahydropyridines as a putative efflux pump inhibitor, including in mycobacteria, being a promising strategy against M. tuberculosis. Thus, we investigated the biological potential of 2,2,2-trifluoro-1-(1,4,5,6-tetrahydropyridin-3-yl)ethanone derivative (NUNL02) against two strains of M. tuberculosis. NUNL02 was able to increase the susceptibility of the multidrug resistant strain to the anti-TB drugs, resulting in synergism with rifampicin. Still, we assume that this compound plays a role in the efflux mechanism in M. tuberculosis, besides, to be able to kill the bacillus under the deprivation of essential nutrients. Thus, our findings highlight NUNL02 as a promising prototype to develop a new adjuvant for TB treatment, mainly as EPI., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The discovery of novel α-glucosidase inhibitors and anti-diabetic candidates from natural or natural-derived products represents an attractive therapeutic option. Here, a collection of acetylphenol analogues derived from paeonol and acetophenone were synthesized and evaluated for their α-glucosidase inhibitory activity. Most of derivatives, such as 9a-9e, 9i, 9m-9n and 11d-1e, (IC 50  = 0.57 ± 0.01 μM to 8.45 ± 0.57 μM), exhibited higher inhibitory activity than the parent natural products and were by far more potent than the antidiabetic drug acarbose (IC 50  = 57.01 ± 0.03 μM). Among these, 9e and 11d showed the most potent activity in a non-competitive manner. The binding processes between the two most potent compounds and α-glucosidase were spontaneous. Hydrophobic interactions were the main forces for the formation and stabilization of the enzyme - acetylphenol scaffold inhibitor complex, and induced the topography image changes and aggregation of α-glucosidase. In addition, everted intestinal sleeves in vitro and the maltose loading test in vivo further demonstrated the α-glucosidase inhibition of the two compounds, and our findings proved that they have significant postprandial hypoglycemic effects., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The first total syntheses of (±)-melicolones A and B, which have a unique and densely functionalized framework derived from a rearranged prenylated acetophenone, were accomplished in 12.3% combined overall yield. The concise and divergent synthesis of these two natural products, which were isolated in racemic form, was achieved in a longest linear sequence requiring only 9 steps (11 total steps) and 8 isolated intermediates using commercially available starting materials. This approach, which might enable access to all tetracyclic melicolones, features the highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition of a carbonyl ylide generated by the unusual cyclization of a rhodium carbene with the carbonyl oxygen atom of an aliphatic aldehyde. This cycloaddition proceeds with dominant steric control to give a highly functionalized oxabicycloheptane core. Stereoselective enolate alkylation led to a prenylated intermediate that underwent an intramolecular aldol reaction to give the penultimate tricyclic intermediate. Tandem epoxidation of the pendant prenyl group followed by a regioselective, acid-catalyzed cyclization delivered (±)-melicolones A and B.

Inspired by the synergistic effect of BTSA1 (a Bax activator) and SAHA (a histone deacetylase (HDAC) inhibitor) in HeLa cell growth suppression, a series of novel HDAC-Bax multiple ligands were designed rationally. Compound 23 , which possesses similar HDAC inhibitory activity relative to SAHA and Bax affinity comparable to BTSA1, exhibits a superior growth suppression against HeLa cells, and its antiproliferative activities are 15-fold and 3-fold higher than BTSA1 and SAHA, respectively. The better antiproliferative activity and lower cytotoxicity of compound 23 indicated that our HDAC-Bax multiple ligand design strategy achieved success. Further studies suggested that compound 23 could enhance Bax-dependent apoptosis by upregulating Bax, followed by inducing the conformational activation of Bax. To our knowledge, we first report HDAC-Bax multiple ligands and demonstrate a new paradigm for the treatment of solid tumors by enhancing Bax-dependent apoptosis.

In this study, compounds with 4-hydroxybutyl, 4-phenyl, 5-carboxylate, and pyrimidine moieties were determined as α-glycosidase inhibitors. N-Substituted pyrimidinethione and acetophenone derivatives (A1-A5, B1-B11, and C1-C11) were good inhibitors of the α-glycosidase enzyme, with K i values in the range of 104.27 ± 15.75 to 1,004.25 ± 100.43 nM. Among them, compound B7 was recorded as the best inhibitor, with a K i of 104.27 ± 15.75 nM against α-glycosidase. In silico studies were carried out to clarify the binding affinity and interaction mode of the compounds with the best inhibition score against α-glycosidase from Saccharomyces cerevisiae. Compounds B7 (S) and B11 (R) exhibited a good binding affinity with docking scores of -8.608 and 8.582 kcal/mol, respectively. The docking results also showed that the 4-hydroxybutyl and pyrimidinethione moieties play a key role in S. cerevisiae and human α-glycosidase inhibition., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

The slow delayed rectifier potassium current (I Ks ) is formed by the KCNQ1 (K v 7.1) channel, an ion channel of four α-subunits that modulates KCNE1 β-subunits. I Ks is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac I Ks cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates I Ks and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved I Ks activators as novel therapeutics for the treatment of LQTS., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Paeonol has been proved to have potential anti-inflammatory activity, but its clinical application is not extensive due to the poor anti-inflammatory activity (14.74% inhibitory activity at 20 μM). In order to discover novel lead compound with high anti-inflammatory activity, series of paeonol derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. Structure-activity relationships (SARs) have been fully concluded, and finally (E)-N-(4-(2-acetyl-5-methoxyphenoxy)phenyl)-3-(3,4,5-trimet-hoxyphenyl)acrylamide (compound 11a) was found to be the best active compound with low toxicity, which showed 96.32% inhibitory activity at 20 μM and IC 50 value of 6.96 μM against LPS-induced over expression of nitric oxide (NO) in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4, resulting in inhibiting of NF-κB and MAPK pathways. Further studies have shown that compound 11a has obvious therapeutic effect against the adjuvant-induced rat arthritis model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Paeonol, 2-hydroxy-4-methoxy acetophenone, is one of the main active ingredients of traditional Chinese medicine such as Cynanchum paniculatum, Paeonia suffruticosa Andr and Paeonia lactiflora Pall. Modern medical research has shown that paeonol has a wide range of pharmacological activities. In recent years, a large number of studies have been carried out on the structure modification of paeonol and the mechanism of action of paeonol derivatives has been studied. Some paeonol derivatives exhibit good pharmacological activities in terms of antibacterial, anti-inflammatory, antipyretic analgesic, antioxidant and other pharmacological effects. Herein, the research progress on paeonol derivatives and their pharmacological activities were systematically reviewed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this article, 23 compounds (6 and 7a-7v) were prepared and evaluated for their in vitro α-glucosidase inhibitory activity. The compounds 7d, 7f, 7i, 7n, 7o, 7r, 7s, 7u, and 7v displayed the α-glucosidase inhibition activity with IC 50 values ranging from 1.68 to 7.88 µM. Among all tested compounds, 7u was found to be the most efficient, being 32-fold more active than the standard drug acarbose, which significantly attenuated postprandial blood glucose in mice. In addition, the compound 7u also induced the fluorescence quenching and conformational changes of enzyme, by forming α-glucosidase-7u complex in a mixed inhibition type. The thermodynamic constants recognised the interaction between 7u and α-glucosidase and was an enthalpy-driven spontaneous exothermic reaction. The synchronous fluorescence and CD spectra also indicate that the compound 7u changed the enzyme conformation. The findings identify the binding interactions between new ligands and α-glucosidase and reveal the compound 7u as a potent α-glucosidase inhibitor.

The isolation of 12 secondary metabolites, including seven new acetophenone monomers, from the 50% CH 3 OH/CH 2 Cl 2 extract (N089419-L/6) of Acronychia trifoliolata was reported previously. In the present work, three new prenylated acetophenone dimers ( 1 - 3 ) and five known dimers ( 4 - 8 ) were isolated, and their structures were elucidated by using various NMR spectroscopic techniques and HRMS. Among the new dimers, an unprecedented 4-isobutyl-3-isopropyltetrahydro-2 H -pyran ring was observed in the structure of 1 . This study is the first to report the formation of a 2 H -pyran ring between two prenylated acetophloroglucinols. Only four related dimers have been reported before, and they were formylated phloroglucinol dimers from the family Eucalypteae. Compounds 2 and 3 are acrovestone-like dimers, and the structure of 3 was confirmed by total synthesis. The evaluation of the antiproliferative activity of isolated and synthesized acrovestone-like dimers indicated that a double bond in the prenyl-like moiety as found in the more active compounds might be important for mediating activity, while the pendant isobutyl group seems to be less important.

T-cell acute lymphoblastic leukemia is an aggressive hematological malignancy originating from the malignant transformation of progenitor T cells at different stages of development. The treatment causes severe adverse effects and is associated with relapses and high morbidity and mortality rates. The present study aimed to evaluate the cytotoxic activity of 28 new compounds containing 3,4,5-trimethoxyphenyl analogues on hematological neoplastic cells lines. Cytotoxicity screening by the MTT method revealed that compound 1d was the most promising. Cell viability of neoplastic cells decreased in a concentration- and time-dependent manner, with compound 1d not causing hemolysis or reducing peripheral blood mononuclear cells viability, suggesting a selective cytotoxicity. We also suggested that compound 1d induced apoptotic-like cell death with mitochondrial involvement in Jurkat cells.

Rottlerin (1) is a potent protein kinase C δ inhibitor that possesses a wide range of biological activities. However, the potential of this molecule to be developed as a drug has been restricted by its limited availability. We report herein a gram scale quantity synthesis of rottlerin in a five-step synthetic route that can be completed within 2 days. The methodology was extended by the reaction of the key aminochromene intermediate (15) with various electron-rich arenes, forming novel unsymmetrical methylene-bridged compounds. The X-ray crystal structure revealed the boomerang shape of this kind of molecule for the first time. The direct transformation of rottlerin (1) into the natural product, isorottlerin (35), was observed for the first time, and we named this transformation the "isorottlerin change". In addition, the antibacterial activities of rottlerin (1) and new rottlerin analogues 32-34 were examined against Staphylococcus aureus. The compounds showed MIC values as low as 2.0 μM, which were comparable to the clinically used antibiotic gentamicin.

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, ¹H NMR, 13 C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one ( 2a ) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one ( 3a ) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P 2₁/ n , and orthorhombic, Pbca , respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π⁻π stack interactions obtained by XRD packing analyses.

Background: Microbial infections is a global public health problem. The aim of this work was to synthesize and evaluate the antimicrobial activity of novel triazoles, morpholines and thiosemicarbazones., Methods: Compounds were synthesized using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. The antimicrobial activity of these compounds against bacteria and yeast was evaluated by the broth microdilution method., Results: The proposed route for synthesis gave high to moderate yields, moreover these compounds were successfully characterized by 1H NMR, 13C NMR and LC-MS. Antimicrobial testing indicated that the thiosemicarbazone and morphine derivatives had the best antimicrobial activity against the microorganisms tested with minimum inhibitory concentrations (MIC) between 0.29 and 5.30 µM. Thiosemicarbazone derivative (12) was able to inhibit the growth of C. tropicalis, with minimum fungicidal concentration (MFC) of 0.55 µM. In addition, this compound was active against E. coli, S. aureus and S. epidermidis, with MIC values ranging from 0.29 to 1.11 µM. Moreover, the morpholine derivative (15) had an MIC value of 0.83 µM against C. albicans and E. coli., Conclusion: We have efficiently synthesized a series of eleven novel triazoles, thiosemicarbazones and morpholine derivatives using 2,4-Dihydroxyacetophenone and 4-hydroxybenzaldehyde as starting materials. Thiosemicarbazone derivative (12) showed promising antifungal and antibacterial activity and these findings suggest that this compound can be used as scaffolds to design new antimicrobial drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acetophenone and its analogues are naturally-occurring compounds found in many foods and plants. In this study, a series of acetophenone benzoylhydrazones 5a-o were designed and synthesized as new potential antioxidant agents. Designed molecules contain hydrazone and phenolic hydroxyl moieties which possibly contribute to antioxidant activity. The antioxidant properties of compounds 5a-o in terms of reducing ability and radical-scavenging activity were assessed by using FRAP and DPPH tests, respectively. While the unsubstituted compound 5a had the superior capacity in the FRAP assay, the 2,4-dihydroxyacetophenone analogue 5g was the most potent radical scavenger in the DPPH method. The antioxidant potential of representative compounds 5a and 5g was further confirmed by TEAC and ORAC assays. Cell viability assays revealed that while the promising compounds 5a and 5g had no significant toxicity against HepG2 and NIH3T3 cells, they potently protected HepG2 cells against H 2 O 2 -induced oxidative damage at low concentrations. Furthermore, spectroscopic studies with different biometals demonstrated that 5g was able to interact with Cu 2+ to form a 1:1 complex., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Dichloroacetophenone is a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor with suboptimal kinase selectivity. Herein, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones. Structure-activity relationship analyses (SARs) enabled us to identify three potent compounds, namely 54, 55, and 64, which inhibited PDK1 function, activated pyruvate dehydrogenase complex, and reduced the proliferation of NCI-H1975 cells. Mitochondrial bioenergetics assay suggested that 54, 55, and 64 enhanced the oxidative phosphorylation in cancer cells, which might contribute to the observed anti-proliferation effects. Collectively, these results suggested that 54, 55, and 64 could be promising compounds for the development of potent PDK1 inhibitors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Magnetic hydroxyapatite (HAp) is being widely investigated for various applications in medical engineering and nanocomposite for transformation reaction. The present work describes an efficient procedure for the synthesis of phenacyl derivatives employing a novel, green and magnetically retrievable nanocomposite via the grafting of β-cyclodextrin moieties on the magnetic hydroxyapatite surface, γ-Fe 2 O 3 @HAp-CD. The structure and composition of the nanocomposite was performed by different methods and analyzed by Infrared Spectroscopy (FT-IR), Field Emission Scanning Electron Microscopy (FE-SEM), transmission electron microscopy (TEM), Thermo-Gravimetric Analysis (TGA), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS) and Brunauer Emmett Teller (BET) and vibrating sample magnetometry (VSM). Our results indicate that conjugation with β-CD improves the catalytic activity in the reaction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a ⁻ g (half maximal inhibitory concentration (IC 50 ) values ranging from 35 μ M to 95 μ M) did not exhibit better inhibitory activity than tHGA ( 3a ) (IC 50 value: 23.6 μ M) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d , with an IC 50 value of 15.3 μ M, exhibited better LOX inhibitory activity when compared to tHGA ( 3a ), which was in agreement with our previous findings. Kinetics study showed that the most active analogue ( 3e ) and tHGA ( 3a ) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues ( 3a ⁻ g ) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.

A series of acetophenone derivatives (10a-10i, 11, 12a-12g, 13a-13g, 14a-14d and 15a-15l) were designed, synthesized and evaluated for antifungal activities in vitro and in vivo. The antifungal activities of 53 compounds were tested against several plant pathogens, and their structure-activity relationship was summarized. Compounds 10a-10f displayed better antifungal effects than two reference fungicides. Interestingly, the most potent compound 10d exhibited antifungal properties against Cytospora sp., Botrytis cinerea, Magnaporthe grisea, with IC 50 values of 6.0-22.6 µg/mL, especially Cytospora sp. (IC 50  = 6.0 µg/mL). In the in vivo antifungal assays, 10d displayed the significant protective efficacy of 55.3% to Botrytis cinerea and 73.1% to Cytospora sp. The findings indicated that 10d may act as a potential pesticide lead compound that merits further investigation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Here, we describe that simple ketones can be efficiently employed as electrophiles in Suzuki-Miyaura coupling reactions via catalytic activation of unstrained C-C bonds. A range of common ketones, such as cyclopentanones, acetophenones, acetone and 1-indanones, could be directly coupled with various arylboronates in high site-selectivity, which offers a distinct entry to more functionalized aromatic ketones. Preliminary mechanistic study suggests that the ketone α-C-C bond was cleaved via oxidative addition.

Ruthenium-based compounds have gained great interest due to their potent cytotoxicity in cancer cells; however, much of their potential applications remain unexplored. In this paper, we report the synthesis of a novel ruthenium complex with xanthoxylin (RCX) and the investigation of its cellular and molecular action in human hepatocellular carcinoma HepG2 cells. We found that RCX exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer cultures and in a 3D model of multicellular cancer spheroids formed from HepG2 cells. This compound is detected at a high concentration in the cell nuclei, induces DNA intercalation and inhibits DNA synthesis, arresting the cell cycle in the S-phase, which is followed by the activation of the caspase-mediated apoptosis pathway in HepG2 cells. Gene expression analysis revealed changes in the expression of genes related to cell cycle control, apoptosis and the MAPK pathway. In addition, RCX induced the phosphorylation of ERK1/2, and pretreatment with U-0126, an MEK inhibitor known to inhibit the activation of ERK1/2, prevented RCX-induced apoptosis. In contrast, pretreatment with a p53 inhibitor (cyclic pifithrin-α) did not prevent RCX-induced apoptosis, indicating the activation of a p53-independent apoptosis pathway. RCX also presented a potent in vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells. Altogether, these results indicate that RCX is a novel anticancer drug candidate.

A series of 7-[4-(trifluoroacetyl)phenyl]-7-deazaadenine and -7-deazaguanine as well as 5-substituted uracil and cytosine 2'-deoxyribonucleosides and mono- and triphosphates were synthesized through aqueous Suzuki-Miyaura crosscoupling of halogenated nucleosides or nucleotides with 4-(trifluoroacetyl)phenylboronic acid. The modified nucleoside triphosphates were good substrates for DNA polymerases applicable in primer extension or PCR synthesis of modified oligonucleotides or DNA. Attempted cross-linking with a serine-containing protein did not proceed, however the trifluoroacetophenone group was a sensitive probe for the study of DNA-protein interactions by 19 F NMR.

Cinnamaldehyde is a natural product with broad spectrum of antibacterial activity. In this work, it was used as a template for design and synthesis of a series of 17 cinnamylideneacetophenones. Phenolic compounds 3 and 4 exhibited MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) values of 77.9 to 312 µM against Staphylococcus aureus , Streptococcus mutans , and Streptococcus sanguinis. Compounds 2 , 7 , 10 , and 18 presented potent effects against Mycobacterium tuberculosis (57.2 µM ≤ MIC ≤ 70.9 µM). Hydrophilic effects caused by substituents on ring B increased antibacterial activity against Gram-positive species. Thus, log P o/w were calculated by using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) analyses, and cinnamylideneacetophenones presented values ranging from 2.5 to 4.1. In addition, the effects of 3 and 4 were evaluated on pulmonary cells, indicating their moderate toxicity (46.3 µM ≤ IC 50 ≤ 96.7 µM) when compared with doxorubicin. Bioactive compounds were subjected to in silico prediction of pharmacokinetic properties, and did not violate Lipinski's and Veber's rules, corroborating their potential bioavailability by an oral route., Competing Interests: The authors declare no conflict of interest.

Oxidative stress is related to the pathogenesis and progress of several human diseases. NADPH oxidase (NOX), and mainly the NOX2 isoform, produces superoxide anions (O 2 • - ). To date, it is known that NOX2 can be inhibited by preventing the assembly of its subunits, p47phox and p22phox. In this work, we analyzed the binding to NOX2 of the apocynin dimer, diapocynin (C1), a known NOX2 inhibitor, and of 18 designed compounds (C2-C19) which have chemical relationships to C1, by in silico methods employing a p47phox structure from the Protein Data Bank (PDB code: 1WLP). C1 and six of the designed compounds were recognized in the region where p22phox binds to p47phox and makes π-π interactions principally with W193, W263, and Y279, which form an aromatic-rich region. C8 was chosen as the best compound according to the in silico studies and was synthesized and evaluated in vitro. C8 was able to prevent the production of reactive oxygen species (ROS) similar to C1. In conclusion, targeting the aromatic region of p47phox through π-interactions is important for inhibiting NOX activity., (© 2017 Deutsche Pharmazeutische Gesellschaft.)

We here present a conceptually novel reaction-based ELISA principle (ReactELISA) for quantitation of the carbon nucleophilic lipid metabolite acetoacetate. Key to the assay is the utilization of a highly chemoselective Friedländer reaction that captures and simultaneously stabilizes the nucleophilic metabolite directly in the biological matrix. By developing a bifunctional biotinylated capture probe, the Friedländer-acetoacetate adduct can be trapped and purified directly in streptavidin coated wells. Finally, we outline the selection and refinement of a highly selective recombinant antibody for specific adduct quantitation. The setup is very robust and, as we demonstrate via miniaturization for microplate format, amenable for screening of compounds or interventions that alter lipid metabolism in liver cell cultures. The assay-principle should be extendable to quantitation of other nucleophilic or electrophilic and perhaps even more reactive metabolites provided suitable capture probes and antibodies.

Background: We have developed a new series of 36 substituted thiazole derivatives prepared via reaction of substituted benzothiazole-2-amine with substituted phenacyl bromide., Objective: This study was aimed to develop and successfully evaluate anti-inflammatory activity of substituted thiazole derivatives., Method: A new series of 36 substituted thiazole derivatives was synthesized and derivatives were characterized by analytical and spectrometric methods like IR, MS, and 1H NMR. The molecular docking was performed for all the synthesized thiazole derivatives to assess their binding affinities to COX-2 isozyme. The best compounds from docking study were subjected for their anti-inflammatory activity by using rat hind paw edema method., Results: Results from carrageenan-induced hind paw edema showed that compounds 3h, 5a, 5e, 9d, and 9h possess significant anti-inflammatory activity. The result from vascular permeability indicating inhibition of vascular permeability with compounds 3h and 9h is significant and results from cotton pellet granuloma formation models show greater degree of inhibition with compounds 3h and 5a to contribute to their significant anti-inflammatory activity., Conclusion: This study provides successful development of novel thiazole derivatives. Their binding affinities to COX-2 enzyme were also confirmed, indicating that developed molecules are comparable to diclofenac and hence could be promising anti-inflammatory agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Six acetophenone derivatives, acronyculatins I (1), J (2), K (3), L (4), N (5), and O (6), were recently isolated from Acronychia trifoliolata, and the structure of the known acronyculatin B (7) was revised. Because of the limited quantities of isolated products as well as their structure similarity, racemic acronyculatins I-L, N, O, and B (1-7) were synthesized to confirm their structures and to obtain sufficient material for biological evaluation. Trihydroxyacetophenone was converted to the target compounds by various sequences of hydroxy group protection, allylation or prenylation, and epoxidation followed by cyclization. C-Prenylations were carried out by direct addition of a prenyl group or through 1,3- or 3,3-sigmatropic rearrangement. The synthesized racemic compounds were evaluated in an anti-tumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds significantly inhibited EBV-EA activation. Especially, racemic acronyculatin I (1) displayed the most potent inhibitory effects, with an IC 50 value of 7.3 μM.

A new series of paeonol alkyl ether analogues were synthesized and confirmed with IR, 1 H NMR, 13 C NMR and HRMS spectra. They have shown anti-inflammatory activities by scavenging mediator of free radicals and inhibiting lipid mediator of inflammation on complete Freund's adjuvant (CFA) induced arthritis in mice. The in vitro and in vivo scavenging ability of free radicals was determined by using chemical analysis and commercial assay kits, respectively. The in vivo inhibiting lipid mediator of inflammation was examined by ELISA. Our results indicated that the substitution of the hydrogen in hydroxyl group at C 2 position of paeonol 1 by short carbon chain, in the presence or absence of bromo atom at C 5 position, decreased its scavenging ability on radicals (3a or 4a vs 1), while the long alkyl substitution (C n >14) increased the activity. Compared with 3a or 4a, scavenging abilities of 3a-h or 4a-h gradually increased following the length elongation of alkyl carbon chain. Compounds 3h and 4h showed great scavenging ability on OH, O 2 - , DPPH, ATBS + and MDA, and good promotion on T-AOC and SOD. The results of the in vivo inhibiting lipid mediator of inflammation also demonstrated that 3h, 4h exhibited substantial inhibition on enzyme activity of COX-2, PGE2. Therefore, 3h and 4h have great potential to be the novel anti-inflammatory drug candidates for the therapy of arthritis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Association of cholinesterase with β-amyloid plaques and tau neurofibrillary tangles in Alzheimer's disease offers an opportunity to detect disease pathology during life. Achieving this requires development of radiolabelled cholinesterase ligands with high enzyme affinity. Various fluorinated acetophenone derivatives bind to acetylcholinesterase with high affinity, including 2,2,2-trifluoro-1-(3-dimethylaminophenyl)ethanone (1) and 1-(3-tert-butylphenyl)-2,2,2-trifluoroethanone (2). Such compounds also offer potential for incorporation of radioactive fluorine ( 18 F) for Positron Emission Tomography (PET) imaging of cholinesterases in association with Alzheimer's disease pathology in the living brain. Here we describe the synthesis of two meta-substituted chlorodifluoroacetophenones using a Weinreb amide strategy and their rapid conversion to the corresponding trifluoro derivatives through nucleophilic substitution by fluoride ion, in a reaction amenable to incorporating 18 F for PET imaging. In vitro kinetic analysis indicates tight binding of the trifluoro derivatives to cholinesterases. Compound 1 has a K i value of 7nM for acetylcholinesterase and 1300nM for butyrylcholinesterase while for compound 2 these values are 0.4nM and 26nM, respectively. Tight binding of these compounds to cholinesterase encourages their development for PET imaging detection of cholinesterase associated with Alzheimer's disease pathology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A series of novel 2,5,7-tricarbo-substituted indoles were prepared via sequential Sonogashira and Suzuki-Miyaura cross-coupling of 2-amino-5-bromo-3-iodoacetophenone with terminal acetylenes and aryl/styrylboronic acids followed by palladium chloride-mediated heteroannulation of the incipient 5-aryl/styryl-substituted 2-amino-3-(arylalkynyl)acetophenones. These polycarbo-substituted indole derivatives were evaluated for potential in vitro antiproliferative activity against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines. Compounds 6f, 6i, 6k, 6m and 6n were found to exhibit significant cytotoxicity and selectivity against the HeLa cells. Compounds 6i and 6m were chosen as representative examples to evaluate their pro-apoptotic efficacy against the HeLa cell line. The compounds induced apoptosis through cell membrane alteration and DNA fragmentation caspase-dependent pathways., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A series of new 2,4-dihydroxy-5-methylacetophenone 2 derivatives were synthesized, and characterized by (1)H, (13)C NMR and ESI-MS. Their antifungal activities were evaluated in vitro against five important plant fungal pathogens including Cytospora sp., Glomerella cingulate, Pyricularia oryzaecar, Botrytis cinerea and Alternaria solani by the mycelial growth inhibitory rate assay. Compounds 2b-d, 2g and 2h displayed a broad-spectrum activity. The logP value of these active compounds is ranging from 1.71 to 2.54. Especially, isopropyl ketone 2g (logP 2.27) was found to be the most active to the tested organisms with IC50 values of 17.28-32.32 μg/mL. The results suggest that compound 2g might be a promising candidate in the development of new agrochemical antifungal agents. Preliminary structure-activity relationship (SAR) studies of the acetophenone derivatives are also discussed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using ¹H-NMR, (13)C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.

The ternary terbium(III) complexes [Tb(HDAP)3⋅biq], [Tb(HDAP)3⋅dmph] and [Tb(HDAP)3⋅bathophen] were prepared by using methoxy substituted hydroxyketone ligand HDAP (2-hydroxy-4,6-dimethoxyacetophenone) and an ancillary ligand 2,2-biquinoline or 5,6-dimethyl-1,10-phenanthroline or bathophenanthroline respectively. The ligand and synthesized complexes were characterised based on elemental analysis, FT-IR and (1)H NMR. Thermal behaviour of the synthesized complexes illustrates the general decomposition patterns of the complexes by thermogravimetric analysis. Photophysical properties such as excitation spectra, emission spectra and luminescence decay curves of the complexes were investigated in detail. The main green emitting peak at 548nm can be attributed to (5)D4→(7)F5 of Tb(3+) ion. Thus, these complexes might be used to make a bright green light-emitting diode for display purpose. In addition the in vitro antibacterial activities of HDAP and its Tb(III) complexes against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and antifungal activities against Candida albicans and Aspergillus niger are reported. The Tb(3+) complexes were found to be more potent antimicrobial agent as compared to the ligand. Among all these complexes, [Tb(HDAP)3⋅bathophen] exhibited excellent antimicrobial activity which proves its potential usefulness as an antimicrobial agent. Furthermore, in vitro antioxidant activity tests were carried out by using DPPH method which indicates that the complexes have considerable antioxidant activity when compared with the standard ascorbic acid., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Coumarin derivatives as dihydrocoumarins have been reported to have multiple biological activities, such as antioxidant and anti-inflammatory properties. Apocynin (APO), which is a substituted-methoxy-catechol, is the most commonly used inhibitor of the multienzymatic complex NADPH-oxidase., Objective: To increase the potency of APO as an NADPH oxidase inhibitor and its antioxidant and anti-inflammatory activities, we synthesized a compound by combining the structural features of a dihydrocoumarin and APO., Method: The dihydrocoumarin-apocynin derivative (HCA) was synthesized and evaluated in antioxidant and cell-based bioassays and compared with APO., Results: We found that HCA (IC50 = 10 µM) acted as an inhibitor of NADPH oxidase (ex vivo assays) and was more potent than APO (EC50 10 µM). The inhibitory effect on NADPH oxidase was not related to simple radical scavenger activity. HCA was also a more effective radical scavenger than APO, as verified in the DPPH (EC50 = 50.3 versus EC50100 µM), triene degradation (slope AUC/concentration 759 ± 100 versus 101 ± 15) and FRAP (slope 0.159 versus 0.015) assays. The tested compound demonstrated a similar activity as an inhibitor of the oxidative damage provoked by peroxyl radicals in erythrocyte membranes., Conclusion: HCA showed superior capacity as inhibitor of NADPH oxidase and antioxidant activity. These findings show that HCA could be an improved substitute for APO and deserves further in vivo anti-inflammatory studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: With the ultimate goal of identifying new compounds active against root-knot nematodes, a set of 14 substituted chalcones were synthesised, starting from acetophenones. These chalcones and various acetophenones were tested in vitro against Meloidogyne incognita., Results: The most potent acetophenones were 4-nitroacetophenone and 4-iodoacetophenone, with EC(50/24 h) values of 12 ± 5 and 15 ± 4 mg L(-1) respectively, somewhat weaker than that of the chemical control fosthiazate in our previous experiments (EC(50/24 h) 0.4 ± 0.3 mg L(-1)). When we converted the acetophenones to chalcones, the nematicidal activity differed, based on their substitution pattern. The condensation of 4-nitroacetophenone with 2,4,6-trihydroxybenzaldehyde to give the corresponding chalcone (E)-1-(4-nitrophenyl)-3-(2,4,6-trihydroxyphenyl)prop-2-en-1-one led to a slight reduction in activity (EC(50/24 h) value 25 ± 17 mg L(-1)). Moreover, (E)-3-(2-hydroxy-5-iodophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one showed better activity (EC(50/24) h value 26 ± 15 mg L(-1)) than 4-methoxyacetophenone (EC(50/24 h) value 43 ± 10 mg L(-1))., Conclusions: Acetophenones and chalcones may represent good leads in the discovery of new nematicidal compounds and may have potential use in crop management as active ingredients., (© 2015 Society of Chemical Industry.)

A series of 17 simple 1-(2,4-dihydroxyphenyl) ethanones were synthesised, and their structures characterised by (1)H, (13)C NMR and ESI-MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi including Glomerella cingulate, Botrytis cirerea, Fusarium graminearum, Curvularia lunata and Fusarium oxysporum f. sp. vasinfectum by the mycelial growth inhibition assay. Compounds 2g and 2h exhibited broad-spectrum inhibitory activity against the mycelial growth of the tested pathogens with IC50 values in the range of 16-36 μg/mL, and in particular being more active to G. cingulate, with IC50 values of 16.50 and 19.25 μg/mL, respectively, than the other pathogens. Preliminary SAR indicated that an α,β-unsaturated ketone unit of the alkyl chain of the compounds is the structure requirement for fungicidal action. The results suggested that 2g and 2h may be promising leads in the development of new antifungal agents.

The first total synthesis of rottlerin is described. The methodology allows the development of potential novel protein kinase C δ (PKCδ) analogues for better treatment of various diseases. Kamalachalcone A and dimeric rottlerin were synthesized in a very practical and economical way using FeCl3 as a catalyst.

Aim: To obtain some chalcones and their dibrominated analogues and to evaluate their antimicrobial potential., Material and Methods: Eight chalcones were synthesized using the Claisen-Schmidt condensation of acetophenone/4-bromo-acetophenone and different benzaldehyde derivatives. These chalcones were further brominated using two different bromination agents: molecular bromine and pyridinium tribromide. The antimicrobial activity was tested using the disk diffusion method., Results and Discussions: The classical bromination technique was compared to the eco-friendly one using pyridinium tribromide. Pyridinium tribromide bromination did not improve the reaction yields (except for one compound), but it had the advantage of being a stable, non-corrosive and non-toxic salt. The results of the antimicrobial assessment indicated that the bromination of the double bond slightly increased the antimicrobial potential in some cases, but the results obtained during the antimicrobial evaluation were modest, some of the derivatives being active especially on Sarcina lutea ATCC 9341 and Bacillus cereus ATCC 14579., Conclusions: In this study, eight chalcones and their dibrominated analogues were synthesized, four of the α,β-dibromochalcones being reported for the first time. Pyridinium tribromide was used as an alternative for liquid bromine, the main advantage of this method being related to the reduced toxicity of the reagents. The synthesized compounds did not exhibit a very good antimicrobial potential.

Based on a previous report that substituted 2-acetylphenols may be promising leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5-substituted 2-acetylphenol analogs (15) and related compounds (two) were synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the study compounds exhibited inhibitory activities against both MAO-A and MAO-B, with selectivity for the B isoform. Among the compounds evaluated, seven compounds exhibited IC50 values <0.01 µM for MAO-B inhibition, with the most selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform. Analyses of the structure-activity relationships for MAO inhibition show that substitution on the C5 position of the 2-acetylphenol moiety is a requirement for MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this regard. This study concludes that C5-substituted 2-acetylphenol analogs are potent and selective MAO-B inhibitors, appropriate for the design of therapies for neurodegenerative disorders such as Parkinson's disease.

2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethan-1-one (bk-2C-B) has been recently offered for purchase by a variety of Internet retailers. This substance may be considered a cathinone analogue of the phenethylamine 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine (2C-B) which suggests that it may have psychoactive effects in humans. A test purchase of bk-2C-B was carried out and its identity was confirmed by a range of analytical techniques including nuclear magnetic resonance spectroscopy, gas and liquid chromatography, and high-resolution mass spectrometry. Confirmation was also obtained from the synthesis of bk-2C-B based on the implementation of the Delépine reaction in which the α-brominated intermediate was reacted with hexamethylenetetramine to afford the primary amine. Analysis of underivatized bk-2C-B by gas chromatography-mass spectrometry (GC-MS) showed that there was potential for artificial formation of 1-(4-bromo-2,5-dimethoxyphenyl)ethanone and a pyrazine dimer, these substances were not detected when employing liquid chromatographic analysis. Ion chromatography and X-ray crystallography analysis confirmed that the purchased bk-2C-B consisted of a hydrochloride and hydrobromide salt mixture, which indicated that it might have been prepared by the hexamethylenetetramine route followed by hydrochloric acid hydrolysis of the quaternary ammonium salt. X-ray crystallography also revealed that the purchased (mixed HCl/HBr salt) and synthesized bk-2C-B (HCl salt) exists as polymorphs., (Copyright © 2014 John Wiley & Sons, Ltd.)

A novel oligomer p-bromoacetophenone-formaldehyde (OPBAF) was prepared by condensation polymerization in the presence of an acid as catalyst. It was characterized by FT-IR, NMR, pyrolysis GC/MS, XRD, GPC, and TG-DTG. The crystallographic parameters and space group for hexagonal OPBAF were a = b = 2.0810 Å and c = 9.2340 Å and P3̅m1, respectively. The degradation activation energy of the oligomer was studied by the Kissinger method. The kinetic parameters were also obtained. Halogen bonding interactions in the crystalline oligomers are identified between halogen···carbonyl and halogen···halogen. Little correlation was found in the halogen bonding motifs exhibited as a function of bromine present in this oligomer, and a unique bifurcated Br···Br/Br···O═C halogen bonding synthon was identified. This newly developed oligomer may be used as an interesting material for the development of 3D-designed structural products.