ABSTRACT
Global agricultural production is significantly hampered by insect pests, and the demand for natural pragmatic pesticides with environmental concern remains unfulfilled. Ageratina adenophora (Spreng.) also known as Crofton weed, is an invasive perennial herbaceous plant that is known to possess multiple bioactive compounds. In our study, two isomers of ageraphorone metabolites i.e, 10â¯Hα-9-oxo-ageraphorone (10HA) and 10â¯Hß-9-oxo-ageraphorone (10HB), were identified from Crofton weed, exhibiting potent antifeedant and larvicidal activities against Plutella xylostella. For antifeedant activity, the median effective concentration (EC50) values for 10HA and 10HB in the choice method were 2279â¯mg/L and 3233â¯mg/L, respectively, and for the no choice method, EC50 values were 1721â¯mg/L and 2394â¯mg/L, respectively. For larvicidal activity, lethal concentration (LC50) values for 10HA and 10HB were 2421â¯mg/L and 4109â¯mg/L at 48â¯h and 2101â¯mg/L and 3550â¯mg/L at 72â¯h. Furthermore, both in- vivo and in-vitro studies revealed that the isomers 10HA and 10HB exhibited potent detoxifying enzymes inhibition activity such as carboxylesterase and glutathione S-transferases. Molecular docking and MD simulation analysis provide insight into the possible interaction between isomers of ageraphorone metabolites and Carboxylic Ester Hydrolase protein (Gene: pxCCE016b) of P. xylostella, which led to a finding that CarEH protein plays a significant role in the detoxification of the two compounds in P. xylostella. Finally, our findings show that the primary enzymes undergoing inhibition by isomers of ageraphorone metabolites, causing toxicity in insects, are Carboxylesterase and glutathione S-transferase.
Subject(s)
Ageratina , Moths , Sesquiterpenes , Ageratina/chemistry , Moths/drug effects , Animals , Insecticides/chemistry , Insecticides/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Larva/drug effects , Molecular Docking Simulation , Binding Sites , Molecular Conformation , Isomerism , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Esterases/chemistry , Esterases/metabolism , Glutathione Transferase/chemistry , Glutathione Transferase/metabolism , Feeding Behavior/drug effectsABSTRACT
Three new spatane diterpenoids (1-3) were isolated from the brown alga Stoechospermum marginatum together with three known compounds (4-6). The structures of these compounds were determined by the detailed NMR spectroscopic and Mass spectrometric analyses. All the isolated compounds were screened for their cytotoxic potentials against a panel of four human cancer cell lines, which include DU145 (Prostate), B16F10 (Melanoma), MDA MB-231 (Breast), and HeLa (Cervical) along with a normal cell line (HEK). The screening results indicated that compounds 1, 4 and 5 displayed significant activities against B16F10 [IC50, 6.21 ± 0.14, 5.88 ± 0.21, 5.31 ± 0.24 µM] and MDA MB-231 [9.25 ± 0.61, 4.59 ± 0.14, 4.19 ± 0.13 µM] cell lines, respectively. In view of their significant activity, these compounds 1, 4 and 5 were further taken up for detailed fluorescence assays, scratch assay and flow cytometry analysis, which revealed that they diminished proliferation and arrested cell cycle in the S phase and G2/M phase, which induced cell death by apoptosis. Overall, based on their considerable results, these compounds could serve as lead molecules in the development of anticancer drug candidates.
Subject(s)
Apoptosis , Diterpenes , Phaeophyceae , Diterpenes/pharmacology , Diterpenes/isolation & purification , Diterpenes/chemistry , Humans , Molecular Structure , Cell Line, Tumor , Phaeophyceae/chemistry , Apoptosis/drug effects , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , China , Antineoplastic Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/chemistryABSTRACT
Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2-12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b, 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions.
Subject(s)
Immunomodulating Agents , Phytochemicals , Tinospora , Tinospora/chemistry , Molecular Structure , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Animals , Mice , Immunomodulating Agents/pharmacology , Immunomodulating Agents/isolation & purification , Coumaric Acids/pharmacology , Coumaric Acids/isolation & purification , Immunologic Factors/pharmacology , Immunologic Factors/isolation & purification , RAW 264.7 Cells , Macrophages/drug effects , Plant Extracts/pharmacology , Plant Extracts/chemistry , Interleukin-6ABSTRACT
The present study was intended for the identification of secondary metabolites in acetone extract of the lichen Hypotrachyna cirrhata using UPLC-ESI-QToF-MS/MS and the detection of bioactive compounds. This study led to the identification of 22 metabolites based on their MS/MS spectra, accurate molecular masses, molecular formula from a comparison of the literature database (DNP), and fragmentation patterns. In addition, potent antioxidant and α-glucosidase inhibitory potentials of acetone extract of H. cirrhata motivated us to isolate 10 metabolites, which were characterized as salazinic acid (11), norlobaridone (12), atranorin (13), lecanoric acid (14), lichesterinic acid (15), protolichesterinic acid (16), methyl hematommate (17), iso-rhizonic acid (18), atranol (19), and methylatratate (20) based on their spectral data. All these isolates were assessed for their free radicals scavenging, radical-induced DNA damage, and intestinal α-glucosidase inhibitory activities. The results indicated that norlobaridone (12), lecanoric acid (14), methyl hematommate (17), and atranol (19) showed potent antioxidant activity, while depsidones (salazinic acid (11), norlobaridone (12)) and a monophenolic compound (iso-rhizonic acid, (18)) displayed significant intestinal α-glucosidase inhibitory activities (p < 0.001), which is comparable to standard acarbose. These results were further correlated with molecular docking studies, which indicated that the alkyl chain of norlobaridione (12) is hooked into the finger-like cavity of the allosteric pocket; moreover, it also established Van der Waals interactions with hydrophobic residues of the allosteric pocket. Thus, the potency of norlobaridone to inhibit α-glucosidase enzyme might be associated with its allosteric binding. Also, MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energies of salazinic acid (11) and norlobaridone (12) were superior to acarbose and may have contributed to their high activity compared to acarbose.
Subject(s)
Antioxidants , Lichens , Antioxidants/chemistry , Lichens/metabolism , Acarbose , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Plant Extracts/pharmacology , Plant Extracts/chemistry , Tandem Mass Spectrometry , Acetone , Glycoside Hydrolase Inhibitors/chemistryABSTRACT
(+)-Usnic acid (UA), a natural dibenzofuran derivative, abundantly produced by lichens and possess wide number of biomedical applications including antibacterial, anti-inflammatory, anti-oxidant and anticancer activities. In the present study, as series of usnic acid derivatives (3a-3i) were synthesised using Mannich reaction assessed for their antioxidant, α-glucosidase, and anticancer activities. The in vitro antioxidant activity showed that compound 3d displayed potent antioxidant activity by scavenging the activities of DPPH and ABTS+. The compounds 3d and 3e showed potent cytotoxic activity against HepG2 cancer cells by arresting the cell cycle at S phase and regulating the Bax/BcL2 expression and subsequently induce the apoptosis. Overall, the results clearly indicated that (+)-usnic acid derivatives bearing secondary amines are useful scaffolds for the development of drug candidates for treatment of oxidative stress mediated cancer and metabolic disorders.
ABSTRACT
A series of 1, 2, 3- triazole hybrids (9a-9n) were synthesised from major phenolic constituent, 4-methoxy ethyl cinnamate (5) isolated from rhizomes of Hedychium spicatum (Sm), a traditional medicinal plant used in variety of disease conditions. All the synthesised analogues were tested for their in vitro antiproliferative potential against HCT 116 (colon cancer), A549 (lung cancer), DU-145 (prostate cancer), Hep G2 (hepatoma) and HEK-293 (normal) cell lines. Among the compounds tested, compounds 9i and 9k potently arrested proliferation of DU-145 (prostate cancer) cell line. Compound 9i displayed 20 times better antiproliferative potential than parent compound and almost identical inhibitory activity to that of the standard drug, doxorubicin. The flow cytometric analysis revealed that 9i arrested cells in G2/M phase of cell cycle and induced apoptosis. Overall, the hybrid derivative 9i was found to be a potential antiproliferative lead against prostate cancer.
Subject(s)
Antineoplastic Agents , Prostatic Neoplasms , Male , Humans , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Triazoles , HEK293 Cells , Rhizome , Cell Proliferation , Drug Screening Assays, Antitumor , Apoptosis , Prostatic Neoplasms/drug therapy , Structure-Activity RelationshipABSTRACT
In connection with our continuous efforts in the synthesis of derivatives from major compounds isolated from traditional medicinal plants, in the present study we have attempted to synthesize the furan-conjugated aloe-emodin derivatives (5a-j) using a three-component reaction. The synthesized derivatives were assessed for anticancer activity against five different cancer cell lines using the in vitro MTT assay and the results showed that most of the derivatives are potent against cancer cells comparing with the control. Compounds 5a and 5e showed excellent activity against all the cancer cells with less than 12.5 µM and arrested the cell cycle at the G0/G1 phase in both CAL27 and SCC9 cells. Compound 5e induces the early apoptosis in CAL27 cells and compounds 5a and 5e induce early and late apoptosis, respectively, in SCC9 cells. Moreover, compounds 5b, 5c, 5i, and 5j showed excellent anti-inflammatory activity in LPS-stimulated RAW 264.7 cells by inhibiting IL-6 production. The molecular docking studies revealed that compound 5e has strong interaction with the CLK kinase and protein kinase II through hydrogen binding Asp325 and Lys290.
Subject(s)
Aloe , Antineoplastic Agents , Emodin , Rheum , Rheum/chemistry , Aloe/chemistry , Rhizome , Molecular Docking Simulation , Anthraquinones/pharmacology , Anthraquinones/chemistry , Antineoplastic Agents/pharmacology , Anti-Inflammatory Agents/pharmacologyABSTRACT
In this study, we propose ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-QToF-MS/MS)-guided metabolite isolation as a choice analytical approach to the ongoing structure−activity investigations of chemical isolates from the edible lichen, Ramalina conduplicans Vain. This strategy led to the isolation and identification of a new depside (5) along with 13 known compounds (1−4, 6−14), most of which being newly described in this lichen species. The structures of the isolates were established by detailed analysis of their spectral data (IR, NMR, and Mass). The acetone extract was further analyzed by UPLC-Q-ToF-MS/MS in a negative ionization mode, which facilitated the identification and confirmation of 18 compounds based on their fragmentation patterns. The antioxidant capacities of the lichen acetone extract (AE) and isolates were measured by tracking DPPH and ABTS free radical scavenging activities. Most isolates displayed marked radical scavenging activities against ABTS while moderate activities were observed against DPPH radical scavenging. Except for atranol (14), oxidative DNA damage was limited by all the tested compounds, with a marked protection for the novel isolated compound (5), as previously noted for the acetone extract (p < 0.001). Furthermore, compound (4) and acetone extract (AE) have inhibited intestinal α-glucosidase enzyme significantly (p < 0.01). Although some phytochemical studies were already performed on this lichen, this study provided new insights into the isolation and identification of bioactive compounds, illustrating interest in future novel analytical techniques.
Subject(s)
Antioxidants , Tandem Mass Spectrometry , Acetone , Antioxidants/chemistry , Ascomycota , Chromatography, High Pressure Liquid/methods , Depsides/analysis , Free Radicals , Hypoglycemic Agents , Phytochemicals/analysis , Plant Extracts/chemistry , alpha-GlucosidasesABSTRACT
BACKGROUND: The fingerprinting and quantification of marker compounds from medicinal plants is a domain of the herbal industry for quality/quantity control parameters. OBJECTIVE: The main objective of this study is the application of the in situ ReactIR technique for measuring the concentration of different components during the extraction process of different medicinal plants. METHOD: In this study we have performed the extraction of two-marker compounds, viz. piperine from Piper nigrum and curcumin from Curcuma longa plants, using various solvents (dichloromethane and methanol). The progress of extraction was monitored using an in situ Fourier transform infrared (FTIR) probe instrument and an automated reactor. RESULTS: In this communication, using the in situ ReactIR technique we developed a method which demonstrates the relative quantification of marker analytes, optimizes extraction time and type of solvents to be used for different analytes during the extraction process. CONCLUSIONS: To the best of our knowledge, this is the first report of relative quantification and structural information of marker compounds during the process of extraction using in situ FTIR. HIGHLIGHTS: The present study highlights the real-time monitoring, in situ quantification, and structural information of marker compounds during the process of extraction of medicinal plants using in situ FTIR.
Subject(s)
Curcumin , Piper nigrum , Plants, Medicinal , Biomarkers , CurcumaABSTRACT
In connection with our continuous efforts to generate new derivatives from lead compounds isolated from traditional medicinal plants, a series of aloe-emodin derivatives (6a-6e) were synthesized and assessed for their potential anticancer activity against a panel of cancer cell lines. The results showed that most of the derivatives are more active than the aloe-emodin and particularly, 6b and 6e manifested potent activity with IC50 values of 1.32 & 1.6 µM and 0.99 & 2.68 µM against MDA-MB-231 and MCF-7 cells, respectively. Moreover, 6b and 6e induce early and late apoptosis as well as arrest the cell cycle at the G2/M phase in MDA-MB-231 cells. In conclusion, the results confirmed that the aloe-emodin derivatives could be a potential drug candidate for better treatment of breast cancer.
ABSTRACT
BACKGROUND: Entada phaseoloides (Linn.) Merr. (Family: Fabaceae) is a well-known, traditional, medicinal plant that has been extensively used in the Ayurvedic system of medicine for centuries to combat a wide range of ailments. OBJECTIVE: The goal of this work was to investigate the bioactive constituents from n-butanol extracts of Entada. phaseoloides and develop a method for the comprehensive characterization of saponins using liquid chromatography with an electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS). METHODS: A hyphenated technique, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), has been proposed to integrate LC and MS together with NMR for structural elucidation. This method allowed comprehensive characterization of saponin glycosides from E. phaseoloides based on their MS/MS fragmentation study. RESULTS: The phytochemical study of E. phaseoloides resulted in the isolation and identification of three bio-active constituents. Further, the UPLC-QTOF-MS/MS method led the structure elucidation of saponin constituents directly from crude extracts via comparison of the exact molecular masses from their MS/MS spectra. Identified common fragments m/z 648, 630, 498, 366, and 204 were used for the screening of saponin components. CONCLUSIONS: The present study summarizes the isolation and identification of bio-compounds from n-butanol extract and the demonstration of UPLC-QTOF-MS/MS analysis for the characterization of compounds in complex crude extracts. To the best of our knowledge, this is the first systematic study in structural characterization on complex saponins and other metabolites from crude extract of E. phaseoloides using UPLC-ESI-QTOF-MSE. HIGHLIGHTS: Rapid analysis and characterizations of three new saponins from E. phaseoloides using UPLC-ESI-QTOF-MSE were tentatively identified based on the mass fragmentation study.
Subject(s)
Fabaceae , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Plant Extracts , Seeds , Spectrometry, Mass, Electrospray IonizationABSTRACT
This study depicts the use of a fiber-optic coupled Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) probe for the in-depth study of arene diazonium salt formation and their utilization in the Heck-Matsuda reaction. The combination of these chemical reactions and in situ IR spectroscopy enabled us to recognize the optimum parameters for arene diazonium salt formation and to track the concentrations of reactants, products and intermediates under actual reaction conditions without time consuming HPLC analysis and the necessity of collecting the sample amid the reaction. Overall advantages of the proposed methodology include precise reaction times as well as identification of keto enol tautomerization in allylic alcohols supporting the 'path a' elimination mechanism in the Heck-Matsuda reaction.
Subject(s)
Diazonium Compounds/chemistry , Diazonium Compounds/chemical synthesis , Spectroscopy, Fourier Transform InfraredABSTRACT
BACKGROUND: Entada phaseoloides is a well-known medicinal plant traditionally used in Ayurvedic medicine for centuries. OBJECTIVE: To evaluate the anti-stress activity of seeds of E. phaseoloides in endoplasmic reticulum stress during chronic restrain stress in mice, based on our preliminary screening. MATERIALS AND METHODS: Mice (n = 6/group) were restrained daily for 6 h in 50 ml polystyrene tubes for 28 days. Methanolic extract of E. phaseoloides (MEEP) (100 and 200 mg/kg, p.o.) and standard drug, imipramine (10 mg/kg i.p.) were administered daily 45 min prior to restrain from day 22-28. Then, forced swim test (FST) was performed to assess despair behavior. Lipid peroxidation (LPO) and antioxidant enzymes Reduced glutathione (GSH), Superoxide dismutase (SOD) were measured in the hippocampus of mice. 78 kDa Glucose-regulated Protein, 94 kDa Glucose-regulated Protein, C/EBP homologous protein, Caspase-12 expression were quantified by Real Time PCR. RESULTS: MEEP significantly reduced the immobility time in FST (P < 0.001). Significant reduction of LPO (P < 0.05) level and restored antioxidant enzymes viz. GSH (P < 0.001) and SOD towards vehicle control group were observed. Down-regulation of genes GRP 78, GRP 94 (P < 0.001), CHOP and Caspase-12 (P < 0.001) as compared to the chronic restrain stress group was evident, which were upregulated following treatment. Isolation of the active components of the seeds revealed the presence of Oleic acid (1), Entadamide A (2), Entadamide A-beta-d-glucopyranoside (3) and 1-O-protocatechuoyl-ß-d-glucose. CONCLUSION: MEEP altered endoplasmic reticulum stress in chronic restrain stressed mice; however, as an antidepressant it showed a weaker response.
ABSTRACT
Bioassay-guided separation of acetone extract from lichen Parmotrema tinctorum (Delise ex Nyl.) Hale led to the isolation of six major phenolic constituents (1-6). Compounds structures were established using NMR and mass spectral techniques. Further, to develop libraries on these scaffolds, a series of semi-synthetic derivatives were prepared (1a-1f, 2a-2b, 3a, 5a) and investigated for their free-radicals (2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)) scavenging and advanced glycation end products (AGEs) formation inhibitory activities. Amongst tested derivatives, 1a, 1d, 1e, 2a, and 5a showed strong ABTS scavenging potentials comparable to Trolox. In addition, these derivatives also manifested moderate AGEs formation inhibitory activities. [Formula: see text].
Subject(s)
Antioxidants , Lichens , Glycation End Products, Advanced , Molecular Structure , Phenols , Plant ExtractsABSTRACT
In continuation of our investigation of pharmacologically-motivated natural products, we have isolated bergenin (1) as a major compound from Mallotus philippensis, which is deployed in different Indian traditional systems of medicine. Here, a series of bergenin-1,2,3-triazole hybrids were synthesized and evaluated for their potentials against a panel of cancer cell lines. Several of the hybrid derivatives were found more potent in comparison to parent compound bergenin (1). Among them, 4j demonstrated potent activity against A-549 and HeLa cell lines with IC50 values of 1.86⯵M and 1.33⯵M, respectively, and was equipotent to doxorubicin. Cell cycle analysis showed that 4j arrested HeLa cells at G2/M phase and lead to accumulation of Cyclin B1 protein. Cell based tubulin polymerization assays and docking studies demonstrated that 4j disrupts tubulin assembly by occupying colchicine binding pocket of tubulin.
Subject(s)
Antimitotic Agents/pharmacology , Antineoplastic Agents/pharmacology , Benzopyrans/chemistry , Chromones/chemical synthesis , Chromones/pharmacology , Mitosis , Triazoles/chemistry , Tubulin Modulators/pharmacology , Tubulin/chemistry , Antimitotic Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Drug Design , Humans , Molecular Docking Simulation , Molecular Structure , Polymerization , Structure-Activity Relationship , Tubulin Modulators/chemical synthesisABSTRACT
Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen Usnea longissima. From our study, 19 compounds were tentatively identified through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and comparison with literature data. In addition, potent cytotoxic activity of U. longissima extract prompted us to isolate four compounds, 18R-hydroxy-dihydroalloprotolichesterinic acid (19), neuropogolic acid (20), barbatic acid (21), and usnic acid (22) from this extract which were adequately identified through mass spectrometry and NMR spectroscopy. All four compounds displayed cytotoxic activity. Barbatic acid (21) manifested doxorubicin equivalent activity against A549 lung cancer cell line with IC50 of 1.78 µM and strong G0/G1 accumulation of cells. Poly ADP-ribose polymerase (PARP) cleavage confirmed that it induced cytotoxic activity via apoptosis. Finally, our work has discerned the depside, barbatic acid (21) from crude extract as a candidate anti-cancer molecule, which induces cell death by stepping up apoptosis.
Subject(s)
Ascomycota/drug effects , Ascomycota/metabolism , Chromatography, High Pressure Liquid , Metabolomics , Phthalic Acids/pharmacology , Secondary Metabolism , Spectrometry, Mass, Electrospray Ionization , Acetone , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line , Chromatography, High Pressure Liquid/methods , Dose-Response Relationship, Drug , Humans , Metabolomics/methods , Molecular Conformation , Molecular Structure , Phthalic Acids/chemistry , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
Boswellia serrata is a widely used herb in Indian systems of medicine and is well known for its potential medicinal properties. A chromatographic method was developed for the analysis and quantification of six boswellic acid marker compounds, i.e., keto boswellic acid (1), 3-O-Acetyl 11-keto ß-boswellic acid (2), É-Boswellic acid (3), ß-Boswellic acid (4), 3-O-Acetyl-É-boswellic acid (5) and 3-O-Acetyl-ß-boswellic acid (6) in commercial herbal products containing B. serrata as an ingredient. Combining UPLC with Q-Tof-MS/MS makes the better identification of secondary metabolites and adulterants in the herbal formulations containing B. serrata in rapid time using fragmentation approach than the traditional approaches. In this study quantification of boswellic acids with UPLC-PDA method was performed as per the pharmacopeia guidelines. Furthermore, minor phytochemical constituents were identified and characterized with the help of LC-Q-Tof-MS/MS fragmentation data and various isoforms of boswellic acids and tirucallic acids in B. serrata oleo-gum-resin extract were identified.
ABSTRACT
Boswellia serrata is a widely used herb in Indian systems of medicine and is well known for its potential medicinal properties. A chromatographic method was developed for the analysis and quantification of six boswellic acid marker compounds, i.e., keto boswellic acid (1), 3-O-Acetyl 11-keto β-boswellic acid (2), ɑ-Boswellic acid (3), β-Boswellic acid (4), 3-O-Acetyl-ɑ-boswellic acid (5) and 3-O-Acetyl-β-boswellic acid (6) in commercial herbal products containing B. serrata as an ingredient. Combining UPLC with Q-Tof-MS/MS makes the better identification of secondary metabolites and adulterants in the herbal formulations containing B. serrata in rapid time using fragmentation approach than the traditional approaches. In this study quantification of boswellic acids with UPLC-PDA method was performed as per the pharmacopeia guidelines. Furthermore, minor phytochemical constituents were identified and characterized with the help of LC-Q-Tof-MS/MS fragmentation data and various isoforms of boswellic acids and tirucallic acids in B. serrata oleo-gum-resin extract were identified.
ABSTRACT
Comparative phytochemical analysis of five lichen species [Parmotrema tinctorum (Delise ex Nyl.) Hale, P. andinum (Mull. Arg.) Hale, P. praesorediosum (Nyl.) Hale, P. grayanum (Hue) Hale, P. austrosinense (Zahlbr.) Hale] of Parmotrema genus were performed using two complementary UPLC-MS systems. The first system consists of high resolution UPLC-QToF-MS/MS spectrometer and the second system consisted of UPLC-MS/MS in Multiple Reaction Monitoring (MRM) mode for quantitative analysis of major constituents in the selected lichen species. The individual compounds (47 compounds) were identified using Q-ToF-MS/MS, via comparison of the exact molecular masses from their MS/MS spectra, the comparison of literature data and retention times to those of standard compounds which were isolated from crude extract of abundant lichen, P. tinctorum. The analysis also allowed us to identify unknown peaks/compounds, which were further characterized by their mass fragmentation studies. The quantitative MRM analysis was useful to have a better discrimination of species according to their chemical profile. Moreover, the determination of antioxidant activities (ABTS+ inhibition) and Advance Glycation Endproducts (AGEs) inhibition carried out for the crude extracts revealed a potential antiglycaemic activity to be confirmed for P. austrosinense.
Subject(s)
Lichens/chemistry , Phytochemicals/analysis , Plant Extracts/analysis , Antioxidants/analysis , Antioxidants/chemistry , Antioxidants/pharmacology , Benzothiazoles/chemistry , Chromatography, High Pressure Liquid , Glycation End Products, Advanced/chemistry , Hypoglycemic Agents/analysis , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , India , Lichens/classification , Molecular Structure , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Sulfonic Acids/chemistry , Tandem Mass SpectrometryABSTRACT
A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38⯵M which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.