A non-cyclic tetrameric structure has been suggested for calcichrome (calcion). This structure is consistent with its mass spectrum, proton NMR spectrum, elemental composition and complexing ability with polyaromatic hydrocarbons in water. The stability constants of the 1:1 complexes formed between calcichrome and seven polyaromatic hydrocarbons in water at room temperature have been measured.
The genus Garcinia is reported to possess antimicrobial, anti-inflammatory, anticancer, hepatoprotective and anti-HIV activities. Garcinia hombroniana in Malaysia is used to treat itching and as a protective medicine after child birth. This study was aimed to isolate the chemical constituents from the bark of G. hombroniana and explore their possible pharmacological potential. Ethyl acetate extract afforded one new (1) and six (2-7) known 3 → 8 rotameric biflavonoids. Their structures were elucidated by UV, IR and NMR (1D and 2D) spectroscopy together with electron ionization/ESI mass spectrometric techniques and were identified as (2R, 3S) volkensiflavone-7-O-rhamnopyranoside (1), volkensiflavone (2), 4″-O-methyl-volkensiflavone (3), volkensiflavone-7-O-glucopyranoside (4), morelloflavone (5), 3″-O-methyl-morelloflavone (6) and morelloflavone-7-O-glucopyranoside (7). The absolute configuration of compound 1 was assigned by circular dichroism spectroscopy as 2R, 3S. The coexistence of conformers of isolated biflavonoids in solution at 25 °C in different solvents was confirmed by variable temperature NMR studies. At room temperature (25 °C), compounds 1-7 exhibited duplicate NMR signals, while at elevated temperature (90 °C), a single set of signals was obtained. Compound 5 showed significant in vitro antioxidant activities against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis-3-ethyl benzthiazoline-6-sulfonic acid radicals. The antibacterial studies showed that compounds 5 and 6 are the most active against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compounds 3 and 6 also showed moderate antituberculosis activity against H38 Rv. Based on the research findings, G. hombroniana could be concluded as a rich source of flavanone-flavone (3 → 8) biflavonoids that exhibit rotameric behaviour at room temperature and display significant antioxidant and antibacterial activities.
Human Epidermal Growth Factor Receptor-1 (EGFR), a transmembrane tyrosine kinase receptor (RTK), has been associated with several types of cancer, including breast, lung, ovarian, and anal cancers. Thus, the receptor was targeted by a variety of therapeutic approaches for cancer treatments. A series of chalcone derivatives are among the most highly potent and selective inhibitors of EGFR described to date. A series of chalcone derivatives were proposed in this study to investigate the intermolecular interactions in the active site utilizing molecular docking and molecular dynamics simulations. After a careful analysis of docking results, compounds 1a and 1d were chosen for molecular dynamics simulation study. Extensive hydrogen bond analysis throughout 7 ns molecular dynamics simulation revealed the ability of compounds 1a and 1d to retain the essential interactions needed for the inhibition, especially MET 93. Finally, MM-GBSA calculations highlight on the capability of the ligands to bind strongly within the active site with binding energies of -44.04 and -56.6 kcal/mol for compounds 1a and 1d, respectively. Compound 1d showed to have a close binding energy with TAK-285 (-66.17 kcal/mol), which indicates a high chance for compound 1d to exhibit inhibitory activity, thus recommending to synthesis it to test its biological activity. It is anticipated that the findings reported here may provide very useful information for designing effective drugs for the treatment of EGFR-related cancer disease.
Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo (6a-j) and azo-azo (8a-j). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates 2a-e with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound 6i with the nitro terminal substituent showed the highest LOI value of 27.54%.
A series of new hexasubstituted cyclotriphosphazene compounds (4a-j) consisting of two Schiff base linking units and different terminal substituents was successfully synthesized and characterized. The structures of these compounds were confirmed using Fourier Transform Infra-Red (FTIR), Nuclear Magnetic Resonance (NMR), and CHN elemental analysis. Polarized optical microscopy (POM) was used to determine their liquid-crystal behavior, which was then further confirmed using differential scanning calorimetry (DSC). Compounds 4a-i with heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, 4-carboxyphenyl, chloro, and nitro terminal ends, respectively, showed the liquid-crystal properties, whereas compound 4j with the amino group was found to be non-mesogenic. The attachment of an electron-donating group in 4j eventually give a non-mesogenic product. The study of the fire-retardant properties of these compounds was done using the limiting oxygen index (LOI). In this study, polyester resin (PE) was used as a matrix for moulding, and the LOI value of pure PE was 22.53%. The LOI value increased to 24.71% when PE was incorporated with 1 wt.% of hexachlorocyclotriphosphazene (HCCP), thus indicating that HCCP has a good fire-retardant properties. The result showed that all the compounds have good agreement in their LOI values. Compound 4i with a nitro terminal group gave the highest LOI value of 28.37%.
Acid-responsive fluorescent compounds were prepared by introducing an ortho-hydroxyphenyl to pyrazoline with a benzothiazole backbone. These compounds demonstrated normal fluorescence photoinduced electron transfer (PET) under neutral conditions but the addition of trifluoroacetic acid showed an arctic blue fluorescence, we verified that a protonation process of nitrogen in the thiazole ring which weakened the ability of thiazole to donate electrons to the pyrazoline and changed the photoinduced electron transfer led to photoinduced electron transfer (PET), which was the mechanism of the fluorescence quenching phenomenon under strongly acidic conditions. The photophysical properties of Benzothiazole pyrazoline exhibited blue emission at 421 nm in aqueous DMSO. The blue shift in the emission was switched by acid in DMSO, showing the compound's distinct fluorescence peak at 554 nm. To investigate solvatochromism, eight different solvents were used. The red-shift emission observed in enhancing the polarity of solvents and emission in DMSO suggested the conformation of the molecule which led to the intramolecular charge transfer by color and emission changes. Furthermore, the probe was also applied using the High-performance liquid chromatography (HPLC) with a UV detector to determine the trifluoroacetic acid in water samples. Interestingly, the method was found to be linear over the range of 10.0 µg L-1 to 250.0 µg L-1 (0.999). Under the optimum condition, the separation of trifluoroacetic acid was achieved in 20 min with the LOD of 1.3 µg L-1 and LOQ of 5.1 µg L-1. This proposed method also showed satisfactory results when applied for the analysis of trifluoroacetic acid in a water sample.
Nucleophilic substitution reaction between 4-hydroxybenzaldehyde and hexachlorocyclotriphosphazene, HCCP formed hexakis(4-formlyphenoxy)cyclotriphosphazene, 1. Intermediates 2a-e was formed from the alkylation reaction of methyl 4-hydroxybenzoate with alkyl bromide which further reduced to form benzoic acid intermediates. Further reaction of 2a-e and other substituted benzoic acid formed 3a-h, which then reduced to give subsequent amines, 4a-h. Other similar reaction was used to synthesis 4i. Condensation reaction between 1 and 4a-i yielded hexasubstituted cyclotriphosphazene compounds, 5a-i having Schiff base and amide linking units, and these compounds consist of different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxy, carboxy, chloro, and nitro groups, respectively. Compound 5j with amino substituent at terminal end was formed from the reduction of 5i. All the intermediates and compounds were characterized using Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and CHN elemental analysis. Mesophase texture of these compounds were determined using Polarized Optical Microscope (POM) and their mesophase transition were further confirmed using Differential Scanning Calorimetry (DSC). Only compounds 5a-e with alkoxy chains exhibited smectic A phase while other intermediates (1, 2a-e, 3a-h, and 4a-i) and final compounds (5f-j) are found to be non-mesogenic with no liquid crystal behaviour. The confirmation of the identity of the SmA phase was determined using XRD analysis. The study on the structure-properties relationship was conducted in order to determine the effect of the terminal group, length of the chains and linking units to the mesophase behaviour of the compounds. Moreover, the fire retardant properties of these compounds were determined using Limiting Oxygen Index (LOI) testing. Polyester resin with LOI value of 22.53% was used as matrix for moulding in the study. The LOI value increased to 24.71% when this polyester resin incorporated with 1 wt% of HCCP. Generally, all the final compounds showed a positive results with LOI value above 27% and the highest LOI value was belonged to compound 5i with 28.53%. The high thermal stability of the Schiff base molecules and the electron withdrawing group of the amide bonds and nitro group enhanced the fire retardant properties of this compound.
A series of liquid crystal molecules with two Schiff base linking units and a cinnamaldehyde core with different terminal groups were synthesized and characterized. The intermediates of 4-heptyloxybenzaldehyde (1a) and 4-dodeyloxybenzaldehyde (1b) were synthesized through the alkylation of 4-hydroxybenzaldehyde with a series of bromoalkane. A condensation reaction of cinnamaldehyde, 1,4-phenylenediamine and a series of substituted benzaldehydes with different terminal groups such as bromo, chloro, hydroxy, cinnamaldehyde, hydrogen, methoxy, heptyloxy and dodecyloxy produced a series of new cinnamaldehyde-based compounds, 2-9, respectively. All these compounds were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and CHN elemental analysis. The liquid crystal properties of these compounds were determined using polarized optical microscopy (POM), and their transitions were further confirmed using differential scanning calorimetry (DSC). Compounds with chloro, bromo, methoxy, heptyloxy, and dodecyloxy substituents are mesogenic compounds with nematic phase behavior. However, the other compounds were found to be non-mesogenic without any mesophase transitions. The structure-property relationship was investigated in order to study the effect of different terminal groups and Schiff base linking units on the liquid crystalline behavior of these compounds.
The title chalcone derivative, C19H20O5, adopts a trans configuration with respect to the olefinic C=C double bond. The 2-hy-droxy-4-methyl-phenyl ring is coplanar with the attached enone bridge [torsion angle = -179.96 (14)°], where this plane is nearly perpendicular to the 2,4,6-tri-meth-oxy-phenyl ring [dihedral angle = 75.81 (8)°]. In the crystal, mol-ecules are linked into chains propagating along [010] by an O-H⋯O hydrogen bond. These chains are further connected into centrosymmetric dimer chains via weak C-H⋯O inter-actions. The conformations of related chalcone derivatives are surveyed and all of these structures adopt a skeleton with two almost orthogonal aromatic rings.
A triflavanone, Garcineflavanone A (1) and a biflavonol, Garcineflavonol A (2) have been isolated from the stem bark of Garcinia atroviridis (Clusiaceae), collected in Peninsular Malaysia. Their structures were established using one and two-dimensional NMR, UV, IR and mass spectrometry and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Molecular docking studies of the isolated compounds were performed using docking procedure of AutoDock to disclose the binding interaction and orientation of these molecules into the active site gorge.
The use of pseudo-infinite methanol in increasing the rate of esterification and transesterification reactions was studied using oil palm trunk (OPT) and sugarcane bagasse (SCB) derived solid acid catalysts. The catalysts were prepared by incomplete carbonisation at 400°C for 8h, followed by sulfonation at 150°C for 15h and characterised using TGA/DTA, XRD, FT-IR, SEM-EDS, EA and titrimetric determinations of acid sites. Under optimal reaction conditions, the process demonstrated rapid esterification of palmitic acid, with FAME yields of 93% and 94% in 45min for OPT and SCB catalysts, respectively. With the process, moisture levels up to 16.7% accelerated the conversion of low FFA oils by sulfonated carbon catalysts, through moisture-induced violent bumping. Moisture assisted transesterification of palm olein containing 1.78% FFA and 8.33% added water gave FAME yield of 90% in 10h, which was two folds over neat oil.
A structural study of epoxidized natural rubber (ENR-50) and its cyclic dithiocarbonate derivative was carried out using NMR spectroscopy techniques. The overlapping (1)H-NMR signals of ENR-50 at δ 1.56, 1.68-1.70, 2.06, 2.15-2.17 ppm were successfully assigned. In this work, the C=S and quaternary carbon of cyclic dithiocarbonate. All other (1)H- and (13)C-NMR chemical shifts of the derivative remain unchanged with respect to the ENR-50.
A series of new mesogenic azomethine diols were successfully synthesized by condensation reactions between various chloroalkanols and N,N'-bis(4-hydroxy)-benzylidene-o-toluidine (1). The structures of these compounds were confirmed by CHN, FT-IR, (1)H-NMR, and (13)C-NMR spectrophotometer. Their thermotropic liquid crystalline behavior was studied using differential scanning calorimetry (DSC) and polarizing optical microscope (POM). 4,4'-di(4-Hydroxybutoxy)-N-benzylidine-o-tolidine (2a) does not exhibit liquid crystalline properties. A nematic texture was observed for mesogenic diols 2b, and 2d, whereas the diol 2c exhibits a smectic mesophase. The increase of terminal alkyl chain in these mesogenic diols leads to a decrease in the transition temperature.
Rhizomes of Curcuma caesia are traditionally used to treat cancer in India. The aim is to isolate chemical constituents from C. caesia rhizomes through bioassay-guided fractionation. The extract, hexanes and chloroform fractions showed effect on MCF-7 and MDA-MB-231cells in cell viability assay. The chromatographic separation afforded germacrone (1), zerumbone (2), furanodienone (3), curzerenone (4), curcumenol (5), zederone (6), curcumenone (7), dehydrocurdione (8) from hexanes fraction and curcuminol G (9), curcuzederone (10), (1S, 10S), (4S,5S)-germacrone-1 (10), 4-diepoxide (11), wenyujinin B (12), alismoxide (13), aerugidiol (14), zedoarolide B (15), zedoalactone B (16), zedoarondiol (17), isozedoarondiol (18) from chloroform fraction. This is first report of compounds 2, 9-13, 15-18 from C. caesia. The study demonstrated compounds 1-4 and 10 are the bioactive compounds. The effect of curcuzederone (10) on MDA-MB-231 cell migration showed significant inhibition in scratch and Transwell migration assays. The results revealed that curcuzederone could be a promising drug to treat cancer.
4-Hydroxytamoxifen (4-OHT), the most common hormone used for the treatment of breast cancer, is a selective estrogen receptor modulator (SERM) inhibitor that acts as an antagonist in breast tissue and a partial agonist in the endometrium. However, the detailed molecular mechanism of 4-OHT structure modification has not been well investigated to date. Herein, molecular docking, molecular dynamics simulations and free energy calculations were performed to explore the mechanisms of the molecular interactions between newly designed benzophenone imines (BIs) and the three forms apo, antagonist and agonist of the human estrogen receptor hERα. The proposed inhibitors were designed by replacing the triarylethylene estrogenic scaffold found in 4-OHT with Schiff base triarylimine derivatives. The antiestrogen scaffold i.e. the O-alkyl side chain in 4-OHT was developed by incorporating an alanine amino acid side chain functionality into the triarylimine scaffold. Docking results reveal that the newly designed BIs bind to the hydrophobic open pocket of the apo and antagonist hERα conformations with higher affinity as compared to the natural and synthetic estrogen estradiol (E2) and 4-OHT. The analysis of the molecular dynamics simulation results based on six different systems of the best docked BI (5c) with hERα receptors demonstrates stable interactions, and the complex undergoes fewer conformational fluctuations in the open apo/antagonist hERα receptors as compared to the case of the closed agonist. In addition, the calculated binding free energies indicate that the main factor that contributes to the stabilization of the receptor-inhibitor complexes is hydrophobic interactions. This study suggests that the development of these Schiff base derivatives may be worth exploring for the preparation of new 4-OHT analogues.
Compounds with a chalcone scaffold-based structure have demonstrated promising anticancer biological activity. However, the molecular interactions between chalcone scaffold-based compounds and breast cancer-associated proteins remain unclear. Through network pharmacology, molecular docking, and molecular dynamics (MD) simulation analyses, compounds with a chalcone scaffold-based structure were evaluated for their interaction with potential breast cancer targets. The compounds were retrieved from the ASINEX database, resulting in 575,302 compounds. A total of 342 compounds with chalcone scaffold-based structures were discovered. From the 342 compounds that was analysed, ten were chosen due to their adherence to Lipinski's rule, having an appropriate range of lipophilicity (LOGP), and topological polar surface area (TPSA), and absence of any toxicity. Based on target intersection, 50 target genes were found and subjected to protein-protein interaction (PPI), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Four target genes were found to be involved in the breast cancer pathway. Consequently, molecular docking was utilised to analyse the molecular interactions between the compounds and four target protein receptors. Compound 211 exhibited the highest binding affinities for the epidermal growth factor receptor (EGFR), fibroblast growth factor receptor 1 (FGFR1), oestrogen receptor (ESR1), and cyclin dependent kinase 6 (CDK6) with values of -8.95 kcal/mol, -8.60 kcal/mol, -10.33 kcal/mol, and -9.90 kcal/mol, respectively. During MD simulation, compound 211 and its respective proteins were stable, compact, and had minimal flexibility. The findings provide foundations for future studies into the interaction underlying the anti-breast cancer potential of compounds with chalcone-based scaffold structures.Communicated by Ramaswamy H. Sarma.
The study aims to investigate various aspects of synthesized mono-chalcone compounds 5 and 8 concerning breast cancer, including network pharmacology, molecular docking, molecular dynamics (MD) simulations, antiproliferative effects, and gene expressions. Initially, the compounds underwent a network pharmacology analysis targeting breast cancer-related targets, with MalaCards, SwissTargetPrediction, and PharmMapper identifying 70 breast cancer target receptors. Subsequently, protein-protein interaction (PPI) network analysis revealed two distinct target gene clusters. Survival analysis identified seven significant target genes following Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) evaluation. Molecular docking and MD simulations were conducted on these seven target genes (AKT2, BRAF, ESR1, FGFR1, IGF1, IGF1R, and KIT), revealing that compound 8 exhibited the highest binding affinities, as well as better stability and compactness when interacting with the targeted proteins. Next, the compounds underwent cell viability assay and gene expression analysis to validate the in silico findings. Both compounds demonstrated the ability to suppress breast cancer proliferation, with compound 8 showing increased selectivity in targeting breast cancer cells while causing minimal harm to normal breast cells. The suppression of breast cancer cell proliferation was attributed to decreased expression levels of AKT2, BRAF, FGFR1, IGF1, IGF1R, KIT, and ESR1. Hence, the results provide insights into the molecular interaction responsible for the anti-breast cancer capabilities of mono-chalcone compounds.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-024-03991-y.
(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-κB signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.
Garcinia species are reported to possess antimicrobial, anti-inflammatory, anticancer, anti-HIV and anti-Alzheimer's activities. This study aimed to investigate the in vitro cholinesterase enzyme inhibitory activities of garcihombronane C (1), garcihombronane F (2), garcihombronane I (3), garcihombronane N (4), friedelin (5), clerosterol (6), spinasterol glucoside (7) and 3β-hydroxy lup-12,20(29)-diene (8) isolated from Garcinia hombroniana, and to perform molecular docking simulation to get insight into the binding interactions of the ligands and enzymes. The cholinesterase inhibitory activities were evaluated using acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. In this study, compound 4 displayed the highest concentration-dependent inhibition of both AChE and BChE. Docking studies exhibited that compound 4 binds through hydrogen bonds to amino acid residues of AChE and BChE. The calculated docking and binding energies also supported the in vitro inhibitory profiles of IC50. In conclusion, garcihombronanes C, F, I and N (1-4) exhibited dual and moderate inhibitory activities against AChE and BChE.