Chalcone Scaffold Research Articles

3D-QSAR, Pharmacophore Modeling, ADMET, and DFT Studies of Halogenated Conjugated Dienones as Potent MAO-B Inhibitors.

It has been reported that the extension of conjugation in chalcone scaffolds considerably enhanced the potency, selectivity, reversibility, and competitive mode of MAO-B inhibition. In this study, using the experimental results of IC50 values of fifteen halogenated conjugated dienone derivatives (MK1-MK15) against MAO-B, we developed a 3DQSAR model. Further, we created a 3D pharmacophore model in active compounds in the series. The built model selected three variables (G2U, RDF115m, RDF155m) among the 653 AlvaDesc molecular descriptors, with a r2 value of 0.87 and a Q2 cv for cross-validation equal to 0.82. The three variables were mostly associated with the direction of symmetry and the likelihood of discovering massive atoms at great distances. The evaluated molecules exhibited a good correlation between experimental and predicted data, indicating that the IC50 value of the structure MK2 was related to the interatomic distances of 15.5 Å between bromine and chloro substituents. Furthermore, the molecules in the series with the highest activity were those with enhanced second component symmetry directional index from the 3D representation, which included the structures MK5 and MK6. Additionally, a pharmacophore hypothesis was developed and validated using the decoy Schrodinger dataset, with an ROC score of 0.87 and an HHRR 1 fitness score that ranged from 2.783 to 3.00. The MK series exhibited a significant blood-brain barrier (BBB) permeability, according to exploratory analyses and in silico projections, and almost all analogues were expected to have strong BBB permeability. Further DFT research revealed that electrostatics were important in the interactions with MAO-B.

Significance of Chalcone Scaffolds in Medicinal Chemistry.

Chalcone is a simple naturally occurring α,β-unsaturated ketone with biological importance, which can also be easily synthesized in laboratories by reaction between two aromatic scaffolds. In plants, chalcones occur as polyphenolic compounds of different frameworks which are bioactive molecules that have been in traditional medicinal practice for many years. Chalcone-based lead molecules have been developed, possessing varied potentials such as antimicrobial, antiviral, anti-inflammatory, anticancer, anti-oxidant, antidiabetic, antihyperurecemic, and anti-ulcer effects. Chalcones contribute considerable fragments to give important heterocyclic molecules with therapeutic utilities targeting various diseases. These characteristic features have made chalcone a topic of interest among researchers and have attracted investigations into this widely applicable structure. This review highlights the extensive exploration carried out on the synthesis, biotransformations, chemical reactions, hybridization, and pharmacological potentials of chalcones, and aims to provide an extensive, thorough, and critical review of their importance, with emphasis on their properties, chemistry, and biomedical applications to boost future investigations into this potential scaffold in medicinal chemistry.

Flavonoid and Chalcone Scaffolds as Inhibitors of BACE1: Recent Updates.

Flavonoids and chalcones are two major classes of chemical moieties that have a vast background of pharmacological activities. Chalcone is a subclass of flavonoids whose therapeutic potential has been implicated due to an array of bioactivities. A lot of research works have shown interest in investigating the neuroprotective effect of these molecules, and have revealed them to be much more potent molecules that can be used to treat neurodegenerative disorders. Beta-site APP cleaving enzyme (BACE1), which is majorly found in the brain, is one of the reasons behind the development of Alzheimer's disease (AD). Flavonoids and chalcones have proven clinical data that they inhibit the production of Aβ plaques that are involved in the progression of AD. In this article, we have provided a detailed chronological review of the research work on the BACE1 inhibiting potency of both flavonoids and chalcones. Almost all the flavonoids and chalcones mentioned in this article have shown very good in vitro and in vivo BACE1 inhibiting activity. The docking studies and the structural importance of some BACE1-inhibiting flavonoids, as well as chalcones, are also mentioned here.

A Comprehensive Review of the Docking Studies of Chalcone for the Development of Selective MAO-B Inhibitors.

Monoamine oxidase B is a crucial therapeutic target for neurodegenerative disorders like Alzheimer's and Parkinson's since they assist in disintegrating neurotransmitters such as dopamine in the brain. Pursuing efficacious monoamine oxidase B inhibitors is a hot topic, as contemporary therapeutic interventions have many shortcomings. Currently available FDA-approved monoamine oxidase inhibitors like safinamide, selegiline and rasagiline also have a variety of side effects like depression and insomnia. In the quest for a potent monoamine oxidase B inhibitor, sizeable, diverse chemical entities have been uncovered, including chalcones. Chalcone is a renowned structural framework that has been intensively explored for its monoamine oxidase B inhibitory activity.The structural resemblance of chalcone (1,3-diphenyl-2-propen-1-one) based compounds and 1,4-diphenyl- 2-butene, a recognized MAO-B inhibitor, accounts for their MAO-B inhibitory activity. Therefore, multiple revisions to the chalcone scaffold have been attempted by the researchers to scrutinize the implications of substitutions onthe molecule's potency. In this work, we outline the docking investigation results of various chalcone analogues with monoamine oxidase B available in the literature until now to understand the interaction modes and influence of substituents. Here we focused on the interactions between reported chalcone derivatives and the active site of monoamine oxidase B and the influence of substitutions on those interactions. Detailed images illustrating the interactions and impact of the substituents or structural modifications on these interactions were used to support the docking results.

Potent Anthelmintic Activity of Chalcones Synthesized by an Effective Green Approach.

There is currently an urgent need for new anthelmintic agents due to increasing resistance to the limited available drugs. The chalcone scaffold is a privileged structure for developing new drugs and has been shown to exhibit potential antiparasitic properties. We synthesized a series of chalcones via Claisen-Schmidt condensation, introducing a novel recoverable catalyst derived from biochar obtained from the pyrolysis of tree pruning waste. Employing microwave irradiation and a green solvent, this approach demonstrated significantly reduced reaction times and excellent compatibility with various functional groups. The result was the generation of a library of functionalized chalcones, exhibiting exclusive (E)-selectivity and high to excellent yields. The chalcone derivatives were evaluated on the free-living nematode Caenorhabditis elegans. The chalcone scaffold, along with two derivatives incorporating a methoxy substituent in either ring, caused a concentration-dependent decrease of worm motility, revealing potent anthelmintic activity and spastic paralysis not mediated by the nematode levamisole-sensitive nicotinic receptor. The combination of both methoxy groups in the chalcone scaffold resulted in a less potent compound causing worm hypermotility at the short term, indicating a distinct molecular mechanism. Through the identification of promising drug candidates, this work addresses the demand for new anthelmintic drugs while promoting sustainable chemistry.

Design, Synthesis, and In vitro Anti-cervical Cancer Activity of a Novel MDM2-p53 Inhibitor Based on a Chalcone Scaffold.

Several novel fluorinated chalcone derivatives were synthesized, and their in vitro anticervical cancer activity and mechanism of action were investigated using the parent nucleus of licorice chalcone as the lead compound backbone and MDM2-p53 as the target. In this study, 16 novel chalcone derivatives (3a-3r) were designed and synthesized by molecular docking technology based on the licorice chalcone parent nucleus as the lead compound scaffold and the cancer apoptosis regulatory target MDM2-p53. The structures of these compounds were confirmed by 1H-NMR, 13C-NMR, and HR-ESI-MS. The inhibitory effects of the compounds on the proliferation of three human cervical cancer cell lines (SiHa, HeLa, and C-33A) and two normal cell lines (H8 and HaCaT) were determined by MTT assay, and the initialstructure-activity relationship was analyzed. Transwell and flow cytometry were used to evaluate the effects of target compounds on the inhibition of cancer cell migration and invasion, apoptosis induction, and cell cycle arrest. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to detect the effects of candidate compounds on mRNA, p53, and Murine double minute 2 (MDM2) protein expression. The binding characteristics of the target compounds to the MDM2 protein target in the p53-MDM2 pathway were evaluated by molecular docking technology. The target compounds had considerable inhibitory activity on the proliferation of three cervical cancer cell lines. Among them, compound 3k (E)-3-(4-(dimethylamino)phenyl)-2-methyl-1-(3-(trifluoromethyl)phenyl) prop-2-en-1-one) showed the highest activity against HeLa cells (IC50=1.08 μmol/L), which was better than that of the lead compound Licochalcone B, and 3k showed lower toxicity to both normal cells. Compound 3k strongly inhibited the migration and invasion of HeLa cells and induced apoptosis and cell cycle arrest at the G0/G1 phase. Furthermore, compound 3k upregulated the expression of p53 and BAX and downregulated the expression of MDM2, MDMX, and BCL2. Moreover, molecular docking results showed that compound 3k could effectively bind to the MDM2 protein (binding energy: -9.0 kcal/mol). These results suggest that the compounds may activate the p53 signaling pathway by inhibiting MDM2 protein, which prevents cancer cell proliferation, migration, and invasion and induces apoptosis and cell cycle arrest in cancer cells. This study provides a new effective and low-toxicity drug candidate from licochalcone derivatives for treating cervical cancer.

Design, synthesis and in silico molecular docking evaluation of novel 1,2,3-triazole derivatives as potent antimicrobial agents

Chalcone and triazole scaffolds have demonstrated a crucial role in the advancement of science and technology. Due to their significance, research has proceeded on the design and development of novel benzooxepine connected to 1,2,3-triazolyl chalcone structures. The new chalcone derivatives produced by benzooxepine triazole methyl ketone 2 and different aromatic carbonyl compounds 3 are discussed in this paper. All prepared compounds have well-established structures to a variety of spectral approaches, including mass analysis, 1H NMR, 13C NMR, and IR. Among the tested compounds, hybrids 4c, 4d, 4i, and 4k exhibited exceptional antibacterial susceptibilities with MIC range of 3.59–10.30 μM against the tested S. aureus strain. Compounds 4c, 4d displayed superior antifungal activity against F. oxysporum with MIC 3.25, 4.89 μM, when compared to fluconazole (MIC = 3.83 μM) respectively. On the other hand, analogues 4d, 4f, and 4k demonstrated equivalent antitubercular action against H37Rv strain with MIC range of 2.16–4.90 μM. The capacity of ligand 4f to form a stable compound on the active site of CYP51 from M. tuberculosis (1EA1) was confirmed by docking studies using amino acids Leu321(A), Pro77(A), Phe83(A), Lys74(A), Tyr76(A), Ala73(A), Arg96(A), Thr80(A), Met79(A), His259(A), and Gln72(A). Additionally, the chalcone‒1,2,3‒triazole hybrids ADME (absorption, distribution, metabolism, and excretion), characteristics of molecules, estimations of toxicity, and bioactivity parameters were assessed.

Novel furan chalcone modulates PHD-2 induction to impart antineoplastic effect in mammary gland carcinoma.

Normoxic inactivation of prolyl hydroxylase-2 (PHD-2) in tumour microenvironment paves the way for cancer cells to thrive under the influence of HIF-1α and NF-κB. Henceforth, the present study is aimed to identify small molecule activators of PHD-2. A virtual screening was conducted on a library consisting of 265,242 chemical compounds, with the objective of identifying molecules that exhibit structural similarities to the furan chalcone scaffold. Further, PHD-2 activation potential of screened compound was determined using in vitro 2-oxoglutarate assay. The cytotoxic activity and apoptotic potential of screened compound was determined using various staining techniques, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, 4',6-diamidino-2-phenylindole (DAPI), 1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), and acridine orange/ethidium bromide (AO/EB), against MCF-7 cells. 7,12-Dimethylbenz[a]anthracene (DMBA) model of mammary gland cancer was used to study the in vivo antineoplastic efficacy of screened compound. [(E)-1-(4-fluorophenyl)-3-(furan-2-yl) prop-2-en-1-one] (BBAP-7) was screened and validated as a PHD-2 activator by an in vitro 2-oxo-glutarate assay. The IC50 of BBAP-7 on MCF-7 cells is 18.84 µM. AO/EB and DAPI staining showed nuclear fragmentation, blebbing and condensation in MCF-7 cells following BBAP-7 treatment. The red-to-green intensity ratio of JC-1 stained MCF-7 cells decreased after BBAP-7 treatment, indicating mitochondrial-mediated apoptosis. DMBA caused mammary gland dysplasia, duct hyperplasia and ductal carcinoma in situ. Carmine staining, histopathology, and scanning electron microscopy demonstrated that BBAP-7, alone or with tirapazamine, restored mammary gland surface morphology and structural integrity. Additionally, BBAP-7 therapy significantly reduced oxidative stress and glycolysis. The findings reveal that BBAP-7 activates PHD-2, making it a promising anticancer drug.

Development of multi-targetable chalcone derivatives bearing N-aryl piperazine moiety for the treatment of Alzheimer's disease

The multi-target directed ligand (MTDL) discovery has been gaining immense attention in the development of therapeutics for Alzheimer’s disease (AD). The strategy has been evolved as an auspicious approach suitable to combat the heterogeneity and the multifactorial nature of AD. Therefore, multi-targetable chalcone derivatives bearing N-aryl piperazine moiety were designed, synthesized, and evaluated for the treatment of AD. All the synthesized compounds were screened for thein vitro activityagainst acetylcholinesterase (AChE), butylcholinesterase (BuChE), β-secretase-1 (BACE-1), and inhibition of amyloid β (Aβ) aggregation. Amongst all the tested derivatives, compound 41bearing unsubstituted benzylpiperazine fragment and para-bromo substitution at the chalcone scaffold exhibited balanced inhibitory profile against the selected targets. Compound 41 elicited favourable permeation across the blood–brain barrier in the PAMPA assay. The molecular docking and dynamics simulation studies revealed the binding mode analysis and protein–ligand stability ofthe compound with AChE and BACE-1. Furthermore,itameliorated cognitive dysfunctions and signified memory improvement in thein-vivobehavioural studies (scopolamine-induced amnesia model). Theex vivobiochemical analysis of mice brain homogenates established the reduced AChE and increased ACh levels. The antioxidant activity of compound 41 was accessed with the determination of catalase (CAT) and malondialdehyde (MDA) levels. The findings suggested thatcompound 41, containing a privileged chalcone scaffold, can act as a lead molecule for developing AD therapeutics.

Antibacterial activity of structurally diverse natural prenylated isobavachalcone derivatives.

Isobavachalcone (IBC) is a natural prenylated flavonoid containing chalcone and prenyl chain moieties with a wide range of biological and pharmacological properties. In this work, we synthesized structurally diversified derivatives (IBC-2 to IBC-10) from the natural prenylated chalcone IBC isolated from Psoralea corylifolia and assessed their antibacterial potency against the Gram-positive and Gram-negative bacterial strains S. aureus ATCC 29213, MRSA ATCC 15187, E. coli ATCC25922 and P. aeruginosa ATCC 27853. IBC and IBC-2 exhibited a minimum inhibition concentration (MIC) of 5.0 μM against S. aureus ATCC 29213, whereas IBC-3 exhibited a broad-spectrum activity against Gram-positive and Gram-negative pathogens. Cytotoxicity assessments on the murine RAW 264.7 macrophage cell line revealed minimal to moderate cytotoxicity for IBC-2 and IBC-3 with a favorable selectivity index (>10). Time- and concentration-dependent studies further supported the bactericidal nature of the compounds, as IBC, IBC-2, and IBC-3 exhibited concentration-dependent killing of S. aureus in a time-dependent manner. Furthermore, combination studies, SEM analysis, and PI staining suggest that IBC-3's mechanism of action targets the bacteria's cytoplasmic membrane or cell wall. The bioactive compounds displayed promising drug-like characteristics and a favorable pharmacokinetic profile (ADME-Tox), indicating a projected high oral bioavailability. Structure-activity relationships (SARs) drawn from this study reveal that a prenyl chain at the A-ring and hydroxy functional groups attached to the aromatic rings of chalcone scaffolds are responsible for this antibacterial potential, which will be helpful in the future discovery and development of antibiotics from natural products to overcome the antibiotic resistance crisis.

Visible‐light‐switchable Chalcone‐Flavylium Photochromic Systems in Aqueous Media

AbstractThe chalcone‐flavylium photochromic system switches in aqueous media. However, the chalcone→flavylium conversion requires detrimental ultra‐violet (UV) light for the switching which deters their applications in the biological domain. To address this issue, we have synthesized strategically modified chalcone scaffolds that can be reversibly switched to the flavylium forms with visible light ranging from 456 nm (blue) to 640 nm (red).

Visible-light-switchable Chalcone-Flavylium Photochromic Systems in Aqueous Media.

The chalcone-flavylium photochromic system switches in aqueous media. However, the chalcone→flavylium conversion requires detrimental ultra-violet (UV) light for the switching which deters their applications in the biological domain. To address this issue, we have synthesized strategically modified chalcone scaffolds that can be reversibly switched to the flavylium forms with visible light ranging from 456 nm (blue) to 640 nm (red).

Synthesis, Docking Studies and Evaluation of Chalcones as Anti-Helicobacter pylori and antitumoral Agents.

Helicobacter pylori colonizes the gastric epithelium of 50 % of world population and it is the main etiological agent of human chronic gastritis, peptic ulcer, and gastric cancer. In this study, we synthesized and characterized a series of 14 chalcones and evaluated their anti-H. pylori, NO inhibition (in vitro and in silico), and AGS cells cytotoxic effects. Compounds 3b and 3h showed MIC of 8 μg/mL. We observed structure-activity relationships, mainly related to the influence of methoxy substituent at C-2 (3b) and the nitro group at C-4 (3h) in chalcone scaffold. The fourteen chalcones inhibited the NO production in LPS-stimulated macrophages and showed potential for interaction on the active site of the iNOS enzyme. Finally, 3b and 3h showed the highest selectivity to the AGS cell lines. Thus, ours results suggest 3b and 3h as potential candidates for design of new and effective agents against H. pylori and related diseases.

Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic Approach through Urease Inhibition, Molecular Docking and Structure-Activity Relationship.

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a-s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were achieved in moderate to good yields (40-70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a-s were condensed with acetophenone via Claisen-Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a-s in excellent yields (85-92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a-s were furnished in good yield (65-90%). Furan chalcone structural motifs 4a-s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a-s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one 4h with an IC50 value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2'-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure-activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones.

Design, Synthesis, Crystal Structure, Biological Activity and Molecular Modeling of Novel Schiff Bases Derived from Chalcones and 5-Hydrazino-1,3-Dimethyl-4-Nitropyrazole as Anticancer Agents

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H2SO4. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC50 among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC50. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents.

Design, Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs.

In search for SDHIs fungicides, twenty-five novel carboxamides containing a chalcone scaffold were designed, synthesized, and evaluated for antifungal activities against five pathogenic fungi. The results showed that compound 5 k exhibited outstanding antifungal activity against R. solani with an EC50 value of 0.20 μg/mL, which was much better than that of commercial SDHIs Boscalid (EC50 =0.74 μg/mL). Moreover, compound 5 k also displayed promising antifungal activities against S. sclerotiorum, B. cinerea, and A. alternate (IC50 =2.53-4.06 μg/mL), indicating that 5 k had broad-spectrum antifungal activity. Additionally, in vivo antifungal activities results showed that 5 k could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (57.78 %) and curative efficacy (58.45 %) at 100 μg/mL, both of which were much better than those of Boscalid, indicating a promising application prospect. Moreover, SEM analysis showed that compound 5 k could remarkably disrupt the typical structure and morphology of R. solani hyphae. Further SDH enzyme inhibition assay and molecular docking study revealed that lead compound 5 k had a similar mechanism of action as commercial SDHI Boscalid. These results indicated that compound 5 k showed potential as a SDHIs fungicide and deserved further investigation.

Newer chalcone scaffolds with reactive functional groups: Process, spectral and single crystal XRD studies

Chalcones are versatile scaffolds for the synthesis of various heterocyclic systems with commercial utility. This work describes the synthesis of five novel chalcone derivatives. Syntheses were performed by a simple one-pot, straightforward Claisen-Schmidt condensation catalyzed with pyrrolidine and KOH. The chalcones were prepared by condensation of 4-formylbenzonitrile with different aromatic ketones at room temperature. The structures of all compounds have been investigated by FT-IR, NMR, and HR-MS spectroscopy. In addition, one chalcone structure was characterized by single-crystal XRD study. Crystal data for C21H15NO2 (Ch2): monoclinic, space group P21/c (no. 14), a = 6.5694(3) Å, b = 33.2697(15) Å, c = 7.4516(4) Å, β = 97.563(2)°, V = 1614.47(14) Å3, Z = 4, T = 293(2) K, μ(MoKα) = 0.083 mm-1, Dcalc = 1.289 g/cm3, 16000 reflections measured (4.898° ≤ 2Θ ≤ 49.99°), 2822 unique (Rint = 0.0249, Rsigma = 0.0196) which were used in all calculations. The final R1 was 0.0484 (I > 2σ(I)) and wR2 was 0.1257 (all data). The absorption maxima of all novel products were evaluated by UV-visible spectroscopy. These well-established structures of all newly prepared chalcone scaffolds with reactive functional groups (i.e. nitrile and 2-propenone) can be exploited as a crucial intermediate in the synthesis of new heterocyclic scaffolds with fluorescence and other applications.

Study on novel biphenyl chalcone scaffolds: A dual spectroscopic approach for efficient sensing of hydrazine with low concentration

Hydrazine and its derivatives, as harmful substances, seriously risk the health of humans and the environment. On the basis of the admirable luminescent properties and low biological harmfulness of the biphenyl moiety, a biphenyl moiety can be combined with a naphthalene ring via the chalcone scaffold easily traced by a nucleophilic group. Therefore, biphenyl chalcones (BPCs) decorated with various naphthalene systems as fluorescent sensors for hydrazine are synthesised by Claisen-Schmidt condensation. The present work describes the comparative studies of two different protocols for the synthesis of three different BPCs. The structures of all novel BPCs were investigated by FT-IR, NMR, and HRMS spectroscopy. These BPCs show a red shift with a fluorescent peak and an enhancement in intensity with increasing solvent polarity from hexane to methanol. Methanol shows strong fluorescence emission; therefore, methanol is used as the solvent in hydrazine sensing experiments. The BPCs display fluorescent variation from yellow to blue fluorescence after binding with hydrazine. These BPCs sensors are able to identify hydrazine in a fast response rate and 5 min response time. The screening study of hydrazine in various soil samples by prepared BPCs is highly efficient. A study of the pH dependence of these probes shows excellent sensitivity in the pH range of 5 to 10.

Antileishmanial activities of three chalcone derivatives and their association with plasma membrane rigidity as assessed by EPR spectroscopy

Novel chalcone-like compounds, LQFM332 (4), LQFM333 (5), and LQFM341 (6), were synthesized and their activity against Leishmania (L.) amazonensis was evaluated and compared. Compound 4 was synthesized from the molecular hybridization of vanillin (9) and butylated hydroxytoluene (BHT), forming a chalcone scaffold. BHT was replaced by another apocynin to give compound 5, while for compound 6 the Michael acceptor double bond from compound 4 was reduced. The IC50 values for compounds 4, 5, and 6 against the Leishmania parasite were 7, 20, and 16 µM for the promastigote form, and 19, 11, and 1 µM for the amastigote form inside infected macrophages, respectively. Electron paramagnetic resonance (EPR) spectroscopy of a lipid spin label incorporated into the parasite plasma membrane demonstrated that treatment with these compounds in culture medium causes membrane rigidity in a concentration-dependent manner, owing to oxidative processes. From the IC50 values with different cell concentrations, the membrane-water partition coefficient (KM/W) of the compounds could be estimated, as well as their concentrations in the membrane (cm50) and in the aqueous culture medium (cw50) that reduce antiproliferative activity by 50%. Values for these biophysical parameters were similar to those reported for the antileishmanial drug, miltefosine. KM/W values indicated that the compounds have high affinity for the parasite membrane, with the compound containing the BHT group having the highest affinity. Compound 5, which contained a two 4-OH-3-methoxybenzene scaffold, showed the lowest values of cw50 and cm50. Compound 6 showed that the reduction of the double bond decreased the membrane affinity and the cw50 value, but maintained the cm50, demonstrating the same activity as compound 4 for assays with higher concentration of cells. As cytotoxic activities were modulated by effects on the cell membrane, our results suggest that the primary action of the compounds is on the parasite membrane.

Analysis of multi-target directed novel non-peptidic chalcone scaffold as potential malaria plasmodium proteases inhibitors

Analysis of multi-target directed novel non-peptidic chalcone scaffold as potential malaria plasmodium proteases inhibitors