3.3 Chemie

Publikationen

1.

Chemical, molecular and structural studies of Boswellia species: β-Boswellic Aldehyde and 3-epi-11β-Dihydroxy BA as precursors in biosynthesis of boswellic acids.

The distribution and biosynthesis of boswellic acids (BAs) is scarce in current literature. Present study aims to elucidate the BAs biosynthetic and its diversity in the resins of Boswellia sacra and Boswellia papyrifera. Results revealed the isolation of new (3β, 11β-dihydroxy BA) and recently known (as new source, β-boswellic aldehyde) precursors from B. sacra resin along with α-amyrin. Following this, a detailed nomenclature of BAs was elucidated. The quantification and distribution of amyrins (3-epi-α-amyrin, β-amyrin and α-amyrin) and BAs in different Boswellia resins showed highest amyrin and BAs in B. sacra as compared with B. serrata and B. papyrifera. Distribution of BAs significantly varied in the resin of B. sacra collected from dry mountains than coastal trees. In B. sacra, high content of α-amyrin was found in the roots but it lacked β-amyrin and BAs. The leaf part showed traces of β-ABA and AKBA but was deficient in amyrins. This was further confirmed by lack of transcript accumulation of amyrin-related biosynthesis gene in leaf part. In contrast, the stem showed presence of all six BAs which are attributed to existence of resin-secretory canals. In conclusion, the boswellic acids are genus-specific chemical constituents for Boswellia species albeit the variation of the amounts among different Boswellia species and grades.

PLoS One. 2018;13(6):e0198666.
PMID: 29912889 [PubMed - as supplied by publisher]

2.

Optimal Processing Conditions of Birdw. Using Response Surface Methodology.

Background: Bridw. is being widely used for its anti-inflammatory properties, as well as for wound healing, antimicrobial, and immunomodulatory properties, and boswellic acids (BAs) are considered to be the main active constituents.

Objectives: To investigate optimal conditions of stir-baking process for the resin of with vinegar of using response surface methodology (RSM).

Materials and Methods: The concentration of acetic acid, heating temperature, and heating time were set as influential factors, and the yields of chemical compounds were the response values which were optimally designed by a Box-Behnken design. The amounts of 11-keto-β-boswellic acid (KBA) and α-boswellic acid (αBA) in resin were quantified using high-performance liquid chromatography analysis.

Results: Maximum amounts of KBA and αBA in resin were obtained using 6% acetic acid for 10 min at 90°C in preliminary test. Two factor interactions, such as acetic acid concentration-heating temperature and heating temperature-heating time, were significantly observed by multiple regression analysis. Optimal processing conditions from RSM were 5.83% for acetic acid concentration, 9.56 min for heating time, and 89.87°C for heating temperature. Under the modified conditions, the experimental value of the response was 11.25 mg/g, which was similar to the predicted value.

Conclusions: The results suggest that the optimal conditions for the stir-baking process of resin were determined by RSM, which was reliable and applicable to practical processing of herbal medicine.

SUMMARY: The resin of was macerated in aqueous acetic acid and heated using an oven for stir baking processThe interaction between heating temperature and heating time was the most significantOptimal conditions for processing resin were determined as 5.83% acetic acid, 9.56 min for heating time, and 89.87°C for heating temperature. BAs: Boswellic acids; KBA: 11 keto β boswellic acid; αBA: α boswellic acid; BBD: Box-Behnken design; RSM: Response surface method; HPLC: High performance liquid chromatography; LOD: Limits of determination; LOQ: Limits of quantification; RSD: Relative standard deviation; ANOVA: Analysis of variance.

Pharmacogn Mag. 2018 Apr-Jun;14(54):235-241.
PMID: 29720838 [PubMed - as supplied by publisher]

3.

New α-Glucosidase inhibitors from the resins of Boswellia species with structure-glucosidase activity and molecular docking studies.

Phytochemical investigation of the oleo-gum resins from Boswellia papyrifera afforded one new triterpene, named 3α-hydroxyurs-5:19-diene (1) together with twelve known compounds including eight triterpenoids (2-9), two diterpenoids (10 and 11) and two straight chain alkanes (12 and 13). Similarly ten more known compounds were isolated from the resin of Boswellia sacra including one triterpene (20) and nine boswellic acids (14-19 and 21-23). Herein the compound 2 was first time reporting from natural source along with complete NMR assignment, while compounds 3-11 are known, but reported for the first time from the resin of B. papyrifera. The structure elucidation was done by advance spectroscopic D and D NMR techniques viz., H, C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. All compounds were evaluated for their α-glucosidase inhibitory activity and as result eight of them 1, 3, 10, 11, 15, and 17-19 were found significantly active against α-glucosidase with an IC value ranging from 15.0 ± 0.84 to 80.3 ± 2.33 µM, while 21 exhibited moderate activity with IC of 799.9 ± 4.98 µM. Furthermore, two compounds 24 and 25 were synthesised from 16 and 17 to see the effect of carboxyl group in structural-activity relationship (SAR) study. Compounds 24 and 25 retained good α-glucosidase inhibition as compared to 16 and 17, indicating that carboxylic group play a key role in SAR. In addition, the aforementioned activity of all the active compounds was first time reported for their α-glucosidase inhibition potential. The molecular docking studies showed that all the active compounds well accommodate in the active site of the enzyme. Moreover pharmacokinetic properties of the compounds were predicted in silico, suggesting that the compounds possess drug like properties and excellent ADMET profile.

Bioorg Chem. 2018 Sep;79():27-33.
PMID: 29715636 [PubMed - as supplied by publisher]

4.

Conformational analysis of macrocyclic frankincense (Boswellia) diterpenoids.

Frankincense oleoresin has been used in traditional medicine for more than 5000 years. The phytochemistry of frankincense (Boswellia spp.) resins includes triterpenoids (including boswellic acids and their derivatives), diterpenoids (cembrenoids and cneorubenoids), and essential oils. The macrocyclic cembrene diterpenoids may play a part in the biological activities of frankincense resin, but neither the biological targets nor the modes of interaction with the targets are currently known. How these macrocycles interact with biological macromolecules likely depends on what conformation(s) are energetically available to them. In this work, a conformational analysis of 15 Boswellia cembrene diterpenoids and 1 verticillane diterpenoid was carried out at the B3LYP/6-31G* and M06-2X/6-31G* levels of theory, including the SM8 aqueous solvation model. The lowest-energy conformations of boscartin B and incensole oxide were the same as the previously reported X-ray crystal structures, while the lowest-energy conformations of boscartins A and C were very similar to the crystal structures. Boscartins D-H and isoincensole oxide showed only one low-energy conformation for each compound and are predicted to be conformationally locked. Incensole, isoincensolol, and serratol are predicted to be conformationally mobile with several low-energy forms. The conformational mobility of Boswellia cembrenoid diterpenoids depends largely on the degree of epoxidation, either oxirane or tetrahydrofuran rings.

J Mol Model. 2018 Mar;24(3):74.
PMID: 29492734 [PubMed - indexed for MEDLINE]

5.

Chemical Composition and Monoterpenoid Enantiomeric Distribution of the Essential Oils from Apharsemon (Commiphora gileadensis).

(Hebrew: apharsemon) has been used since Biblical times to treat various ailments, and is used today in the traditional medicine of some Middle Eastern cultures. The essential oils from the stem bark, leaves, and fruits of -collected at the Ein Gedi Botanical Garden, Israel-were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. In addition, the enantiomeric distributions of the monoterpenoids in the essential oils have been determined by chiral gas chromatography. The essential oils were dominated by monoterpene hydrocarbons, followed by oxygenated monoterpenoids. The major components in oils were the monoterpenes α-pinene (11.1-18.4%), sabinene (15.8-35.9%), β-pinene (5.8-18.0%), -cymene (4.8-8.4%), limonene (1.3-6.2%), γ-terpinene (0.7-8.1%), and terpinen-4-ol (5.3-18.5%). The (-)-enantiomers predominated for α-pinene, sabinene, β-pinene, limonene, and terpinen-4-ol. The chemical compositions of the essential oils from Israel are markedly different from previously reported samples, which were rich in sesquiterpenoids. Likewise, the enantiomeric distribution of monoterpenoids is very different from spp. essential oils.

Medicines (Basel). 2017 Sep;4(3):.
PMID: 28930280 [PubMed - as supplied by publisher]

6.

New water soluble glycosides of 11-keto-β-boswellic acid: A paradigm.

Though several glycosides of various triterpenes are known, but surprisingly no boswellic acid glycosides are reported so far. With a view to make water soluble boswellic acids, prepared glycosides of 11-keto boswellic acid for the first time. Naturally occurring boswellic acids which are anti-inflammatory agents are lipophylic in nature and thus, become a limiting factor in terms of their bioavailability. Among boswellic acids, 11-keto-β-boswellic acid is found to exhibit superior biological activity and hence successfully prepared its glucosyl and maltosyl derivatives viz., 11-keto-β-boswellic acid-24-O-β-D-glucopyranoside (9) and 11-keto-β-boswellic acid-24-O-α-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (15) which are water soluble. Both these compounds are soluble in water to the extent of 10% (w/w) which is very significant.

Nat Prod Res. 2018 Jan;32(2):154-161.
PMID: 28627258 [PubMed - indexed for MEDLINE]

7.

Extraction and purification of five terpenoids from olibanum by ultrahigh pressure technique and high-speed countercurrent chromatography.

Five terpenoids, including two new ones, 3,7-dioxo-tirucalla-8,24-dien-21-oic acid (2) and 3α-acetoxyl-7-oxo-tirucalla-8,24-dien-21-oic acid (3), and three known ones, boscartol A (1), 11-keto-β-boswellic acid (4), and acetyl-11-keto-boswellic acid (5), have been extracted by the ultrapressure extraction and purified by pH-zone-refining countercurrent chromatography and high-speed countercurrent chromatography from olibanum. For ultrapressure extraction, the optimal condition including 200 MPa of extraction pressure, ethyl acetate of extraction solvent, 1:20 (g/mL) of solid/liquid ratio, and 2 min of extraction time were obtained. For the separation, from 1.5 g of the terpenoid extract, 220.1 mg of 4, 255.5 mg of 5, and 212.3 mg of the mixture of 1, 2, and 3 were obtained by pH-zone-refining countercurrent chromatography under the solvent system of chloroform/ethyl acetate/methanol/water (3:1:3:2, v/v/v/v) with aqueous ammonia and trifluoroacetic acid as retention and eluter agents. The enriched mixture (210 mg) was further separated by conventional high-speed countercurrent chromatography with petroleum ether/ethyl acetate/methanol/water (1:0.8:1.1:0.6, v/v/v/v), yielding 30.1 mg of 1, 35.5 mg of 2, 12.3 mg of 3. The structures of these five terpenoids were elucidated by extensive spectroscopic methods.

J Sep Sci. 2017 Jul;40(13):2732-2740.
PMID: 28544633 [PubMed - indexed for MEDLINE]

8.

Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities.

A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (H, C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC: 19.53, 20.31 and 44.14μg/mL). The computational studies revealed that selectivity of AKBA is due to its fitment into the 5-LOX receptor, which is missing for the other enzymes like 12-LOX, COX-1 and COX-2. Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position.

Bioorg Med Chem. 2017 02;25(4):1374-1388.
PMID: 28110820 [PubMed - indexed for MEDLINE]

9.

Design and synthesis of novel 2-substituted 11-keto-boswellic acid heterocyclic derivatives as anti-prostate cancer agents with Pin1 inhibition ability.

A series of novel acetyl-11-keto-β-boswellic acid (AKBA) derivatives with a different electron-withdrawing group on ring A and a nitrogen heterocycle at C-24 were designed and synthesized. These semi-synthetic compounds showed improved anti-proliferative activity against prostate cancer cells over AKBA. Compound 8f bearing 2-cyano-3,11-dioxo moiety and piperazine was the most potent to inhibit growth of prostate cancer PC-3 (IC = 0.04 μM) and LNCaP (IC = 0.27 μM) cell lines. 8f caused cell cycle arrest in G2/M and induced apoptosis. 8f decreased the protein levels of anti-apoptosis protein Mcl-1, c-FLIP and cell cycle regulating protein cyclin D1. 8f inhibited the activity of Pin1, a peptidyl-prolyl cis-trans isomerase to stabilize cyclin D1. 8f represented a compound with improved anti-proliferative effects for prostate cancer therapy working through new mechanisms.

Eur J Med Chem. 2017 Jan;126():910-919.
PMID: 27997878 [PubMed - indexed for MEDLINE]

10.

Ring A-modified Derivatives from the Natural Triterpene 3-O-acetyl-11-keto-β-Boswellic Acid and their Cytotoxic Activity.

BACKGROUND: Natural triterpene boswellic acids (BAs) have attracted much interest due to their anticancer activity, but more chemical modification is necessary to explore their pharmacological value. In addition to subtle functionalization, transformations that alter the triterpene skeleton are viewed as an alternative approach.

OBJECTIVE: In this study, transformations altering ring A of 3-O-acetyl-11-keto-β-boswellic acid (AKBA) were performed to obtain A-lactone, A-lactam, A-seco and A-contracted derivatives.

METHOD: Thirty-two new derivatives were synthesized, and their structures were confirmed by NMR and MS. Their anticancer activity against human cancer cell lines K562, PC3, A549 and HL60 was screened.

RESULTS: Biological evaluation indicated that the ring A cleavage or contraction transformations themselves did not significantly enhance the cytotoxic activity, but most of the derivatives based on these ring A-modified skeletons exhibited good cytotoxic activity. Significantly improved cytotoxicity was discovered for the esterified analogues of the A-lactone and A-lactam series and the amidated analogues of the A-seco and ring A contracted series, especially those bearing two nitrogen-containing substituents. Among them, compounds 6a, 11b, 12k and 18e showed strong cytotoxic activity, with IC50 values of 5.0~3.5 μM against K562 cells, almost ninefold stronger than that of AKBA. Further study proposed that the antiproliferative activities of 6a, 11b, 12k and 18e may be due to apoptosis induction.

CONCLUSION: The transformations of the ring A skeleton of AKBA provide new platforms to discover anticancer candidates.

Anticancer Agents Med Chem. 2017;17(8):1153-1167.
PMID: 27928954 [PubMed - indexed for MEDLINE]

11.

Chemical constituents from twigs of Euonymus alatus.

To investigate the chemical compounds from the twigs of Euonymus alatus, nine compounds were isolated and identified as(+)-delta(2,11)-enaminousnic acid(1), 11-keto-beta-boswellic acid(2), acetyl 11-keto-beta-boswellic acid(3), camaldulenic acid(4), betulinic acid(5), 6beta-hydroxy-stigmast-4-en-3-one(6), 5-hydroxy-6,7-dimethoxyflavone(7), ethyl 2,4-dihydroxy-6-methylbenzoate(8), 4,4'-dimethoxy-1,1'-biphenyl(9). Their structures were elucidated by extensive spectroscopic analysis. Among them, compound 1 was a new natural product. Compounds 2-4 and 7-9 were obtained from the Euonymus genus for the first time. In vitro study showed that compounds 2 and 3 showed significant anti-tumor activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1). The inhibition rate of compound 2 was 61.78% and 68.29%, whereas the inhibition rate of compound 3 had reached to 70.91% and 84.07%.

Zhongguo Zhong Yao Za Zhi. 2015 Jul;40(13):2612-6.
PMID: 26697687 [PubMed - indexed for MEDLINE]

12.

Synthesis of β-boswellic acid derivatives as cytotoxic and apoptotic agents.

A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of apoptosis confirmed by loss of mitochondrial membrane potential, DAPI staining, Western blotting and ROS generation.

Bioorg Med Chem Lett. 2016 Jan;26(1):76-81.
PMID: 26608550 [PubMed - indexed for MEDLINE]

13.

Combination of quantitative analysis and chemometric analysis for the quality evaluation of three different frankincenses by ultra high performance liquid chromatography and quadrupole time of flight mass spectrometry.

Frankincense has gained increasing attention in the pharmaceutical industry because of its pharmacologically active components such as boswellic acids. However, the identity and overall quality evaluation of three different frankincense species in different Pharmacopeias and the literature have less been reported. In this paper, quantitative analysis and chemometric evaluation were established and applied for the quality control of frankincense. Meanwhile, quantitative and chemometric analysis could be conducted under the same analytical conditions. In total 55 samples from four habitats (three species) of frankincense were collected and six boswellic acids were chosen for quantitative analysis. Chemometric analyses such as similarity analysis, hierarchical cluster analysis, and principal component analysis were used to identify frankincense of three species to reveal the correlation between its components and species. In addition, 12 chromatographic peaks have been tentatively identified explored by reference substances and quadrupole time-of-flight mass spectrometry. The results indicated that the total boswellic acid profiles of three species of frankincense are similar and their fingerprints can be used to differentiate between them.

J Sep Sci. 2015 Oct;38(19):3324-30.
PMID: 26228790 [PubMed - indexed for MEDLINE]

14.

Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents.

Methyl esters of the β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) obtained from Boswellia serrata resin were subjected to Steglich esterification with the different non-steroidal anti-inflammatory drugs (NSAID) viz., ibuprofen, naproxen, diclophenac and indomethacin. The novel hybrids of methyl boswellate (5-8) and that of methyl 11-keto boswellate (9-12) were evaluated for anti-inflammatory activity by carrageenan-induced rat hind paw edema model and anti-arthritic activity by Complete Freund's Adjuvant (CFA) induced arthritis in Wister albino rat. Significant inhibition on carrageenan-induced paw edema has been observed with 5, 6 and 10 where as in CFA induced rats, hybrids 5, 8, 9 and 12 exhibited pronounced antiarthritic activity. Hybrid molecules 5 and 9 have been found to be more effective in inhibiting in-vivo COX-2 than ibuprofen by itself, thus showing the synergistic effect. Hybrid 5 and 9 tested for in-vitro lipoxygenase and cyclooxygenase-2 (LOX/COX-2) inhibitory activity. The studies revealed that both 5 and 9 inhibited COX-2 relatively better than LOX enzyme.

Eur J Med Chem. 2015 Jun;98():170-8.
PMID: 26010018 [PubMed - indexed for MEDLINE]

15.

Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study.

CONTEXT: Boswellic acid consists of a series of pentacyclic triterpene molecules that are produced by the plant Boswellia serrata. The potential applications of Bowsellic acid for treatment of cancer have been focused here.

AIMS: To predict the property of the bowsellic acid derivatives as anticancer compounds by various computational approaches.

MATERIALS AND METHODS: In this work, all total 65 derivatives of bowsellic acids from the PubChem database were considered for the study. After energy minimization of the ligands various types of molecular descriptors were computed and corresponding two-dimensional quantitative structure activity relationship (QSAR) models were obtained by taking Andrews coefficient as the dependent variable.

STATISTICAL ANALYSIS USED: Different types of comparative analysis were used for QSAR study are multiple linear regression, partial least squares, support vector machines and artificial neural network.

RESULTS: From the study geometrical descriptors shows the highest correlation coefficient, which indicates the binding factor of the compound. To evaluate the anticancer property molecular docking study of six selected ligands based on Andrews affinity were performed with nuclear factor-kappa protein kinase (Protein Data Bank ID 4G3D), which is an established therapeutic target for cancers. Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound.

CONCLUSIONS: Along with QSAR study and docking result, it was predicted that bowsellic acid can also be treated as a potential anticancer compound.

J Pharm Bioallied Sci. 2015 Jan-Mar;7(1):21-5.
PMID: 25709332 [PubMed - as supplied by publisher]

16.

Synthesis and antitumor activity of ring A modified 11-keto-β-boswellic acid derivatives.

Beta-boswellic acids are interesting triterpenoic acids that show different biological activities. Their cytotoxic potential, as well as that of their derivates remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-β-boswellic acid that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Thus, the introduction of an amino group at position C-2 led to a significantly improved cytotoxic activity of amine 18. An apoptotic effect of compound 18 was determined using DNA laddering and trypan blue staining experiments.

Eur J Med Chem. 2015 Mar;92():700-11.
PMID: 25618017 [PubMed - indexed for MEDLINE]

17.

Genomic sequencing and microsatellite marker development for Boswellia papyrifera, an economically important but threatened tree native to dry tropical forests.

Microsatellite (or simple sequence repeat, SSR) markers are highly informative DNA markers often used in conservation genetic research. Next-generation sequencing enables efficient development of large numbers of SSR markers at lower costs. Boswellia papyrifera is an economically important tree species used for frankincense production, an aromatic resinous gum exudate from bark. It grows in dry tropical forests in Africa and is threatened by a lack of rejuvenation. To help guide conservation efforts for this endangered species, we conducted an analysis of its genomic DNA sequences using Illumina paired-end sequencing. The genome size was estimated at 705 Mb per haploid genome. The reads contained one microsatellite repeat per 5.7 kb. Based on a subset of these repeats, we developed 46 polymorphic SSR markers that amplified 2-12 alleles in 10 genotypes. This set included 30 trinucleotide repeat markers, four tetranucleotide repeat markers, six pentanucleotide markers and six hexanucleotide repeat markers. Several markers were cross-transferable to Boswellia pirrotae and B. popoviana. In addition, retrotransposons were identified, the reads were assembled and several contigs were identified with similarity to genes of the terpene and terpenoid backbone synthesis pathways, which form the major constituents of the bark resin.

AoB Plants. 2015 Jan;7():.
PMID: 25573702 [PubMed - as supplied by publisher]

18.

Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death.

The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.

Bioorg Med Chem Lett. 2014 Oct;24(19):4729-4734.
PMID: 25176189 [PubMed - indexed for MEDLINE]

19.

Retracted: Chemistry and biology of essential oils of genus boswellia.


Evid Based Complement Alternat Med. 2014;2014():605304.
PMID: 25024730 [PubMed - as supplied by publisher]

20.

Micropropagation and non-steroidal anti-inflammatory and anti-arthritic agent boswellic acid production in callus cultures of Boswellia serrata Roxb.

Micropropagation through cotyledonary and leaf node and boswellic acid production in stem callus of a woody medicinal endangered tree species Boswellia serrata Roxb. is reported. The response for shoots, roots and callus formation were varied in cotyledonary and leafy nodal explants from in vitro germinated seeds, if inoculated on Murshige and Skoog's (MS) medium fortified with cytokinins and auxins alone or together. A maximum of 8.0 ± 0.1 shoots/cotyledonary node explant and 6.9 ± 0.1 shoots/leafy node explants were produced in 91 and 88 % cultures respectively on medium with 2.5 μM 6-benzyladenine (BA) and 200 mg l(-1) polyvinylpyrrolidone (PVP). Shoots treated with 2.5 μM IBA showed the highest average root number (4.5) and the highest percentage of rooting (89 %). Well rooted plantlets were acclimatized and 76.5 % of the plantlets showed survival upon transfer to field conditions. Randomly amplified polymorphic DNA (RAPD) analysis of the micropropagated plants compared with mother plant revealed true-to-type nature. The four major boswellic acid components in calluses raised from root, stem, cotyledon and leaf explants were analyzed using HPLC. The total content of four boswellic acid components was higher in stem callus obtained on MS with 15.0 μM IAA, 5.0 μM BA and 200 mg l(-1) PVP. The protocol reported can be used for conservation and exploitation of in vitro production of medicinally important non-steroidal anti-inflammatory metabolites of B. serrata.

Physiol Mol Biol Plants. 2013 Jan;19(1):105-16.
PMID: 24381442 [PubMed - as supplied by publisher]

21.

11α-Ethoxy-β-boswellic acid and nizwanone, a new boswellic acid derivative and a new triterpene, respectively, from Boswellia sacra.

A new boswellic acid derivative, 11α-ethoxy-β-boswellic acid (EBA; 1) and a new ursane-type triterpene, named nizwanone (2), were isolated from Omani frankincense Boswellia sacra Flueck. together with two known compounds papyriogenin B and rigidenol. The structures of 1 and 2 were elucidated by detailed spectroscopic analysis using (1) H- and (13) C-NMR, (1) H,(1) H-COSY, HMQC, HMBC, and HR-EI-MS techniques. The relative configurations of 1 and 2 were assigned by comparative analysis of the NMR spectral data with those of known analogs together with NOESY experiments. Structures of known compounds were identified by comparison with the reported data.

Chem Biodivers. 2013 Aug;10(8):1501-6.
PMID: 23939798 [PubMed - indexed for MEDLINE]

22.

Chemistry and biology of essential oils of genus boswellia.

The properties of Boswellia plants have been exploited for millennia in the traditional medicines of Africa, China, and especially in the Indian Ayurveda. In Western countries, the advent of synthetic drugs has obscured the pharmaceutical use of Boswellia, until it was reported that an ethanolic extract exerts anti-inflammatory and antiarthritic effects. Frankincense was commonly used for medicinal purposes. This paper aims to provide an overview of current knowledge of the volatile constituents of frankincense, with explicit consideration concerning the diverse Boswellia species. Altogether, more than 340 volatiles in Boswellia have been reported in the literature. In particular, a broad diversity has been found in the qualitative and quantitative composition of the volatiles with respect to different varieties of Boswellia. A detailed discussion of the various biological activities of Boswellia frankincense is also presented.

Evid Based Complement Alternat Med. 2013;2013():140509.
PMID: 23533463 [PubMed - as supplied by publisher]

23.

Synthesis of an antitumor active endoperoxide from 11-keto-beta-boswellic acid.

An endoperoxide was synthesized starting from 11-keto-beta-boswellic acid and screened for antitumor activity in a panel of 15 human cancer cell lines by an SRB assay. The compound induces apoptosis and shows an average IC(50) value of 0.4-4.5 microM.

Eur J Med Chem. 2010 Sep;45(9):3840-3.
PMID: 20538386 [PubMed - indexed for MEDLINE]

24.

Comparative study of the chemical composition and antioxidant activity of six essential oils and their components.

The antioxidant activities and the determined major components of six popular and commercially available herb essential oils, including lavender (Lavendular angustifolia), peppermint (Mentha piperita), rosemary (Rosmarius officinalis), lemon (Citrus limon), grapefruit (Citrus paradise), and frankincense (Boswellia carteri), were compared. The essential oils were analysed by GC-MS and their antioxidant activities were determined by testing free radical-scavenging capacity and lipid peroxidation in the linoleic acid system. The major components of the essential oils of lavender, peppermint, rosemary, lemon, grapefruit, and frankincense were linalyl acetate (28.2%), menthol (33.4%), 1,8-cineole (46.1%), limonene (64.5 and 94.2%), and p-menth-2-en-ol (34.5%), respectively. The highest DPPH radical-scavenging activity was obtained by the lavender essential oil and limonene, with RC50 values of 2.1 +/- 0.23% and 2.1 +/- 0.04%, respectively. Radical-scavenging activity against the ABTS radical was highest in peppermint essential oil (1.6 +/- 0.09). Lavender oil was most effective for inhibiting linoleic acid peroxidation after 10 days.

Nat Prod Res. 2010;24(2):140-51.
PMID: 20077307 [PubMed - indexed for MEDLINE]

25.

Absolute stereostructures of olibanumols A, B, C, H, I, and J from olibanum, gum-resin of Boswellia carterii, and inhibitors of nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages.

Three new monoterpenes, olibanumols A (1), B (2), and C (3), and three new triterpenes, olibanumols H (4), I (5), and J (6), were isolated from olibanum, the exuded gum-resin from Boswellia carterii BIRDW. Their structures including the absolute configuration were determined by chemical and physicochemical evidence. Among the constituents, olibanumols A (1), H (4), and I (5), and isofouquierol (12) exhibited nitric oxide production inhibitory activity in lipopolysaccharide-activated mouse peritoneal macrophages.

Chem Pharm Bull (Tokyo). 2009 Sep;57(9):957-64.
PMID: 19721256 [PubMed - indexed for MEDLINE]

26.

Chemical modifications of natural triterpenes - glycyrrhetinic and boswellic acids: evaluation of their biological activity.

Synthetic analogues of naturally occurring triterpenoids; glycyrrhetinic acid, arjunolic acid and boswellic acids, by modification of A-ring with a cyano- and enone- functionalities, have been reported. A novel method of synthesis of α-cyanoenones from isoxazoles is reported. Bio-assays using primary mouse macrophages and tumor cell lines indicate potent anti-inflammatory and cytotoxic activities associated with cyanoenones of boswellic acid and glycyrrhetinic acid.

Tetrahedron. 2008 Dec;64(51):11541-11548.
PMID: 20622928 [PubMed - as supplied by publisher]

27.

Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids.

4-Amino analogues prepared from beta-boswellic acid and 11-keto-beta-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules. The same molecules also exhibited apoptotic activity by inducing DNA fragmentation.

Bioorg Med Chem Lett. 2007 Dec;17(23):6411-6.
PMID: 17950603 [PubMed - indexed for MEDLINE]

28.

Chemistry and immunomodulatory activity of frankincense oil.

The yield of steam distillation of frankincense essential oil (3%); and its physicochemical constants were determined. Capillary GC/MS technique was used for the analysis of the oil. Several oil components were identified based upon comparison of their mass spectral data with those of reference compounds published in literature or stored in a computer library. The oil was found to contain monoterpenes (13.1%), sesquiterpenes (1%), and diterpenes (42.5%). The major components of the oil were duva-3,9,13-trien-1,5alpha-diol-1-acetate (21.4%), octyl acetate (13.4%), o-methyl anisole (7.6%), naphthalene decahydro-1,1,4a-trimethyl-6-methylene-5-(3-methyl-2-pentenyl) (5.7%), thunbergol (4.1%), phenanthrene-7-ethenyl-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydro-1,1,4a,7-tetramethyl (4.1%), alpha-pinene (3.1%), sclarene (2.9%), 9-cis-retinal (2.8%), octyl formate (1.4%), verticiol (1.2%) decyl acetate (1.2%), n-octanol (1.1%). The chemical profile of the oil is considered as a chemotaxonomical marker that confirmed the botanical and geographical source of the resin. Biologically, the oil exhibited a strong immunostimulant activity (90% lymphocyte transformation) when assessed by a lymphocyte proliferation assay.

Z Naturforsch C. 2003 Mar-Apr;58(3-4):230-8.
PMID: 12710734 [PubMed - indexed for MEDLINE]

29.

3-Acetoxy group of genuine AKBA (acetyl-11-keto-beta-boswellic acid) is alpha-configurated.

The pentacyclic triterpenoid 3-acetyl-11-keto-beta-boswellic acid (AKBA) from the resin of Boswellia spec. is a potent inhibitor of 5-lipoxygenase (5-LO). We noticed discrepancies in the nomenclature and stereochemistry of the 3-acetoxy group of boswellic acids. Isolation of AKBA under mild conditions and the data from the first X-ray crystallography study evidence the 3 alpha-orientation of AKBA's acetoxy function.

Planta Med. 2000 Dec;66(8):781-2.
PMID: 11199146 [PubMed - indexed for MEDLINE]

30.

Synthesis of beta-Boswellic acid analogues with a carboxyl group at C-17 isolated from the bark of Schefflera octophylla.


J Org Chem. 2000 Sep;65(19):6278-82.
PMID: 10987979 [PubMed - indexed for MEDLINE]

31.

Workup-dependent formation of 5-lipoxygenase inhibitory boswellic acid analogues.

Pentacyclic triterpenes from the 11-keto-boswellic acid series were identified as the active principal ingredients of Boswellia resin, inhibiting the key enzyme of leukotriene biosynthesis, 5-lipoxygenase (5-LO). Of the genuine boswellic acids hitherto characterized, 3-O-acetyl-11-keto-beta-boswellic acid, AKBA (1), proved to be the most potent inhibitor of 5-LO. In the course of purification of further boswellic acid derivatives from Boswellia resin, we observed the degradation of the natural compound 3-O-acetyl-11-hydroxy-beta-boswellic acid (2) to the thermodynamically more stable product 3-O-acetyl-9, 11-dehydro-beta-boswellic acid (4). The metastable intermediate of this conversion, under moderate conditions of workup in methanolic solutions, was identified as 3-O-acetyl-11-methoxy-beta-boswellic acid (3). The novel artifactual boswellic acid derivatives inhibited 5-LO product formation in intact cells with different characteristics: 4 almost totally abolished 5-LO activity, with an IC(50) of 0.75 microM, whereas 3 and 9,11-dehydro-beta-boswellic acid (5), the deacetylated analogue of 4, were incomplete inhibitors. The data suggest that the conditions chosen for the workup of Boswellia extracts could significantly influence the potency of their biological actions and their potential therapeutic effectiveness.

J Nat Prod. 2000 Aug;63(8):1058-61.
PMID: 10978197 [PubMed - indexed for MEDLINE]

32.

Structure-activity relationships of the nonredox-type non-competitive leukotriene biosynthesis inhibitor acetyl-11-keto-β-boswellic acid.

Acetyl-11-keto-β-boswellic acid (AKBA) from Boswellia serrata Roxb. and italics Boswellia carterii Birdw. is the first selective, direct, non-competitive and non-redox-type inhibitor of 5-lipoxygenase, the key enzyme for leukotriene biosynthesis (Safayhi et al., 1992). Previously, we showed that AKBA interacts with the 5-lipoxygenase via a pentacyclic triterpene selective effector site (Safayhi et al., 1995). In order to study the impact of AKBA's functional groups on enzyme inhibition, natural and synthetic analogues of this boswellic acid were tested for 5-lipoxygenase inhibition in intact rat neutrophils (Sailer et al., 1996 a). The results reveal that the carboxylic group of AKBA combined with the 11-keto-group is essential for enzyme inhibition, whereas the acetoxy-group on position C-3 α increases the affinity of AKBA to its effector site. Furthermore, other experiments demonstrated that minor structural modifications could cause a total loss of binding affinity and/or inhibitory activity of these compounds.

Phytomedicine. 1996 May;3(1):73-4.
PMID: 23194865 [PubMed - as supplied by publisher]

33.

Isolation and structure of a 4-O-methyl-glucuronoarabinogalactan from Boswellia serrata.


Carbohydr Res. 1992 Jan;223():321-7.
PMID: 1596930 [PubMed - indexed for MEDLINE]

34.

CHEMICAL STANDARDIZATION OF 'KUNDUR' (Oleo-Gum-Resin of Boswellia serrata Roxb).

A comparative study of the original and market samples of the KUNDUR (Oleo-Gum-Resin of Boswellia serrata Roxb.) with special reference to its chemical standardization and the qualitative and quantitative studies have been discussed here.

Anc Sci Life. 1984 Jul;4(1):48-50.
PMID: 22557448 [PubMed - as supplied by publisher]