Publikation
Khan, M. F.; Nasr, F. A.; Noman, O. M.; Alyhya, N. A.; Ali, I.; Saoud, M.; Rennert, R.; Dube, M.; Hussain, W.; Green, I. R.; Basudan, O. A. M.; Ullah, R.; Anazi, S. H.; Hussain, H.; Cichorins D–F: Three New Compounds from Cichorium intybus and Their Biological Effects Molecules 25, 4160, (2020) DOI: 10.3390/molecules25184160
Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., β-sitosterol (4), β-sitosterol β-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing’s sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1–3 did not show any promising anthelmintic effects.
Publikation
Jouda, J.-B.; Njoya, E. M.; Fobofou, S. A. T.; Zhou, Z. Y.; Qiang, Z.; Mbazoa, C. D.; Brandt, W.; Zhang, G.-l.; Wandji, J.; Wang, F.; Natural Polyketides Isolated from the Endophytic Fungus
Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating
the ERK/IκBα Signaling Pathways Planta Med. 86, 1032-1042, (2020) DOI: 10.1055/a-1212-2930
AbstractThree previously undescribed natural products, phomopsinin A – C
(1 – 3), together with three known compounds, namely,
cis-hydroxymellein (4), phomoxanthone A (5) and
cytochalasin L-696,474 (6), were isolated from the solid culture of
Phomopsis sp. CAM212, an endophytic fungus obtained from Garcinia
xanthochymus. Their structures were determined on the basis of
spectroscopic data, including IR, NMR, and MS. The absolute configurations of
1 and 2 were assigned by comparing their experimental and
calculated ECD spectra. Acetylation of compound 1 yielded 1a, a
new natural product derivative that was tested together with other isolated
compounds on lipopolysaccharide-stimulated RAW 264.7 cells. Cytochalasin
L-696,474 (6) was found to significantly inhibit nitric oxide production,
but was highly cytotoxic to the treated cells, whereas compound 1
slightly inhibited nitric oxide production, which was not significantly
different compared to lipopolysaccharide-treated cells. Remarkably, the
acetylated derivative of 1, compound 1a, significantly inhibited
nitric oxide production with an IC50 value of 14.8 µM and no
cytotoxic effect on treated cells, thereby showing the importance of the acetyl
group in the anti-inflammatory activity of 1a. The study of the mechanism
of action revealed that 1a decreases the expression of inducible nitric
oxide synthase, cyclooxygenase 2, and proinflammatory cytokine IL-6 without an
effect on IL-1β expression. Moreover, it was found that 1a exerts
its anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7
macrophage cells by downregulating the activation of ERK1/2 and by preventing
the translocation of nuclear factor κB. Thus, derivatives of phomopsinin
A (1), such as compound 1a, could provide new anti-inflammatory
leads.
Publikation
Hussain, H.; Ali, I.; Elizbit, .; Hussain, W.; Mamadalieva, N. Z.; Hussain, A.; Ali, M.; Ahmed, I.; Ullah, I.; Green, I. R.; Synthetic Studies towards Fungal glycosides: An Overview Curr. Org. Chem. 24, 2865-2901, (2020) DOI: 10.2174/1385272824999201105160034
Fungi have provided intriguing chemical diversity and have additionally proven to
be a tremendous source for a great variety of therapeutic molecules. Various fungal glycosides
have been reported from fungi and the majority of these metabolites possess cytotoxic and
antimicrobial effects. Although natural products are obtained in most cases in small amounts
from the specific natural source, total syntheses of these valuable commodities remain one of
the most important ways of obtaining them on a large scale for more detailed and comprehensive
biological studies. In addition, the total synthesis of secondary metabolites is a useful
tool, not only for the disclosure of novel complex pharmacologically active molecules but also
for the establishment of cutting-edge methodologies in synthetic chemistry. Numerous fungal
glycosides have been synthesized in the last four decades regarding the following natural
product classes viz., tetramic acid glycosides (epicoccamides A and D), polyketide glycosides (TMC-151C), 2-pyrone
glycosides (epipyrone A), diterpene glycosides (sordarin), depside glycosides (CRM646-A and –B, KS-501 and KS-
502), caloporosides (caloporoside A), glycolipids (emmyguyacins A and B, acremomannolipin A), and cerebrosides
(cerebroside B, Asperamide B, phalluside-1, Sch II). The current literature review about fungal glycoside synthetic
studies is, therefore, of interest for a wide range of scientists and researchers in the field of organic, natural product,
and medicinal chemists as it outlines key strategies of fungal glycosides and, in particular, glycosylation, the known
biological and pharmacological effects of these natural compounds have afforded a new dimension of exposure.
Publikation
Hussain, W.; Batool, S.; Bahar, S.; Shahida, B.; Bangash, B.; Ali, A.; Hussain, H.; Ali, I.; Ali, M.; Bussmann, R. W.; Ethnopharmacological survey of herbal remedies used in the treatment of hepatitis Ethnobot. Res. App. 20, 1-29, (2020) DOI: 10.32859/era.20.24.1-29
Background: Hepatitis is a serious illness and can be fatal, which has
caused a dangerous ratio round the globe especially in the developed and underdeveloping countries. About 1.4 million deaths are reported each year from the different types of hepatitis especially hepatitis B virus (HBV) and hepatitis C virus (HCV) which cause 90% mortality and the other 10% deaths are caused due to all other hepatitis types. Methods: By using different online database such as Google scholar, Science Direct Navigator, ISI Web of Knowledge, Elsevier, springer link, Test databases, research gate and PubMed, date were retrieved by giving different keywords. Various keywords were used on plants used
traditionally to treat hepatitis. Results: A total of 128 medicinal
plant species were identified, belonging to 108 genera and 61 botanical
families by reviewing 220 research articles. From the study, it showed
that the medicinal plants are used from the very ancient time to cure
hepatitis worldwide. These medicinal plants are used in different parts
of the world as a traditional herbal medicine for the control of
hepatitis. Conclusion: Our literature review will help the scientific
communities to identify anti-hepatitis plant in order to isolate novel
anti-hepatitis natural products.
Publikation
Hussain, H.; Ali, I.; Wang, D.; Mamadalieva, N. Z.; Hussain, W.; Csuk, R.; Loesche, A.; Fischer, L.; Staerk, D.; Anam, S.; AlZain, M. N.; Mushtaq, M.; Ul-Haq, Z.; Ullah, R.; Noman, O. M.; Abbas, G.; Green, I. R.; 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects Biomolecules 10, 1562, (2020) DOI: 10.3390/biom10111562
Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), β-sitosterol (6), and β-sitosterol β-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki′ of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).
Publikation
Humpierre, A. R.; Zanuy, A.; Saenz, M.; Garrido, R.; Vasco, A. V.; Pérez-Nicado, R.; Soroa-Milán, Y.; Santana-Mederos, D.; Westermann, B.; Vérez-Bencomo, V.; Méndez, Y.; García-Rivera, D.; Rivera, D. G.; Expanding the Scope of Ugi Multicomponent Bioconjugation to Produce Pneumococcal Multivalent Glycoconjugates as Vaccine Candidates Bioconjugate Chem. 31, 2231-2240, (2020) DOI: 10.1021/acs.bioconjchem.0c00423
Conjugate vaccines against encapsulated pathogens like Streptococcus pneumoniae face many challenges, including the existence of multiple serotypes with a diverse global distribution that constantly requires new formulations and higher coverage. Multivalency is usually achieved by combining capsular polysaccharide–protein conjugates from invasive serotypes, and for S. pneumoniae, this has evolved from 7- up to 20-valent vaccines. These glycoconjugate formulations often contain high concentrations of carrier proteins, which may negatively affect glycoconjugate immune response. This work broadens the scope of an efficient multicomponent strategy, leading to multivalent pneumococcal glycoconjugates assembled in a single synthetic operation. The bioconjugation method, based on the Ugi four-component reaction, enables the one-pot incorporation of two different polysaccharide antigens to a tetanus toxoid carrier, thus representing the fastest approach to achieve multivalency. The reported glycoconjugates incorporate three combinations of capsular polysaccharides 1, 6B, 14, and 18C from S. pneumoniae. The glycoconjugates were able to elicit functional specific antibodies against pneumococcal strains comparable to those shown by mixtures of the two monovalent glycoconjugates.
Publikation
Holzmeyer, L.; Hartig, A.-K.; Franke, K.; Brandt, W.; Muellner-Riehl, A. N.; Wessjohann, L. A.; Schnitzler, J.; Evaluation of plant sources for antiinfective lead compound discovery by correlating phylogenetic, spatial, and bioactivity data Proc. Natl. Acad. Sci. U.S.A. 117, 12444-12451, (2020) DOI: 10.1073/pnas.1915277117
The continued high rates of using antibiotics in healthcare and livestock, without sufficient new compounds reaching the market, has led to a dramatic increase in antimicrobial resistance, with multidrug-resistant bacteria emerging as a major public health threat worldwide. Because the vast majority of antiinfectives are natural products or have originated from them, we assessed the predictive power of plant molecular phylogenies and species distribution modeling in the search for clades and areas which promise to provide a higher probability of delivering new antiinfective compound leads. Our approach enables taxonomically and spatially targeted bioprospecting and supports the battle against the global antimicrobial crisis.
Publikation
Guerra, T.; Schilling, S.; Hake, K.; Gorzolka, K.; Sylvester, F.-P.; Conrads, B.; Westermann, B.; Romeis, T.; Calcium‐dependent protein kinase 5 links calcium‐signaling with N‐Hydroxy‐L‐pipecolic acid‐ and SARD1‐dependent immune memory in systemic acquired resistance New Phytol. 225, 310-325, (2020) DOI: 10.1111/nph.16147
Systemic acquired resistance (SAR) prepares infected plants for faster and stronger defense activation upon subsequent attacks. SAR requires an information relay from primary infection to distal tissue and the initiation and maintenance of a self‐maintaining phytohormone salicylic acid (SA)‐defense loop.In spatial and temporal resolution, we show that calcium‐dependent protein kinase CPK5 contributes to immunity and SAR. In local basal resistance, CPK5 functions upstream of SA synthesis, perception, and signaling. In systemic tissue, CPK5 signaling leads to accumulation of SAR‐inducing metabolite N‐hydroxy‐L‐pipecolic acid (NHP) and SAR marker genes, including Systemic Acquired Resistance Deficient 1 (SARD1)Plants of increased CPK5, but not CPK6, signaling display an ‘enhanced SAR’ phenotype towards a secondary bacterial infection. In the sard1‐1 background, CPK5‐mediated basal resistance is still mounted, but NHP concentration is reduced and enhanced SAR is lost.The biochemical analysis estimated CPK5 half maximal kinase activity for calcium, K50 [Ca2+], to be c. 100 nM, close to the cytoplasmic resting level. This low threshold uniquely qualifies CPK5 to decode subtle changes in calcium, a prerequisite to signal relay and onset and maintenance of priming at later time points in distal tissue. Our data explain why CPK5 functions as a hub in basal and systemic plant immunity.
Publikation
Gladchuk, A.; Shumilina, J.; Kusnetsova, A.; Bureiko, K.; Billig, S.; Tsarev, A.; Alexandrova, I.; Leonova, L.; Zhukov, V. A.; Tikhonovich, I. A.; Birkemeyer, C.; Podolskaya, E.; Frolov, A.; High-Throughput Fingerprinting of Rhizobial Free Fatty Acids by Chemical Thin-Film Deposition and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Methods Protoc. 3, 36, (2020) DOI: 10.3390/mps3020036
Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and signaling compounds in cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative content of free fatty acids (FFAs). In this context, nitrogen-fixing bacteria (order Rhizobiales), the symbionts of legumes, are particularly interesting. Indeed, the FA profiles influence the structure of rhizobial nodulation factors, required for successful infection of plant root. Although FA patterns can be assessed by gas chromatography—(GC-) and liquid chromatography—mass spectrometry (LC-MS), sample preparation for these methods is time-consuming and quantification suffers from compromised sensitivity, low stability of derivatives and artifacts. In contrast, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by combination of Langmuir technology and MALDI-TOF-MS featuring a high sensitivity, accuracy and precision of quantification. We describe a step-by-step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. As a case study, a comparison of the FFA metabolomes of two rhizobia species—Rhizobium leguminosarum and Sinorhizobium meliloti, demonstrates the analytical potential of the protocol.
Publikation
Fellenberg, C.; Corea, O.; Yan, L.; Archinuk, F.; Piirtola, E.; Gordon, H.; Reichelt, M.; Brandt, W.; Wulff, J.; Ehlting, J.; Constabel, C. P.; Discovery of salicyl benzoate UDP‐glycosyltransferase, a central enzyme in poplar salicinoid phenolic glycoside biosynthesis Plant J. 102, 99-115, (2020) DOI: 10.1111/tpj.14615
The salicinoids are anti‐herbivore phenolic glycosides unique to the Salicaceae (Populus and Salix). They consist of a salicyl alcohol glucoside core, which is usually further acylated with benzoic, cinnamic, or phenolic acids. While salicinoid structures are well known, their biosynthesis remains enigmatic. Recently, two enzymes from poplar, salicyl alcohol benzoyl transferase and benzyl alcohol benzoyl transferase, were shown to catalyze the production of salicyl benzoate, a predicted potential intermediate in salicinoid biosynthesis. Here, we used transcriptomics and co‐expression analysis with these two genes to identify two UDP‐glucose dependent glycosyltransferases (UGT71L1 and UGT78M1) as candidate enzymes in this pathway. Both recombinant enzymes accepted only salicyl benzoate, salicyl aldehyde, and 2‐hydroxycinnamic acid as glucose acceptors. Knocking out the UGT71L1 gene by CRISPR/Cas9 in poplar hairy root cultures led to the complete loss of salicortin, tremulacin, and tremuloidin, and a partial reduction of salicin content. This demonstrated that UGT71L1 is required for synthesis of the major salicinoids, and suggested that an additional route can lead to salicin. CRISPR/Cas9 knockouts for UGT78M1 were not successful, and its in vivo role thus remains to be determined. Although it has a similar substrate preference and predicted structure as UGT71L1, it appears not to contribute to the synthesis of salicortin, tremulacin, and tremuloidin, at least in roots. The demonstration of UGT71L1 as an enzyme of salicinoid biosynthesis will open up new avenues for the elucidation of this pathway.