
Guido PauliUniversity of Illinois Chicago | UIC · Department of Medicinal Chemistry and Pharmacognosy
Guido Pauli
Dr. rer. nat.
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Publications (442)
The therapeutic potential of plant‐derived proanthocyanidins (PACs) interacting with mammalian collagen is extensive, notably in strengthening specialized extracellular matrix like the dentin matrix, crucial for reparative dental treatments. This study unveils an additional facet of PACs beyond their recognized chemical and biomechanical advantages...
This exploratory study was designed to identify factors implicating microbial influence on medicinal plant metabolomes. Utilizing a whole-microbiome approach, amplicon sequencing was used to identify the makeup of fungal and bacterial assemblages from endophytic (interior) and epiphytic (external) environments in two different sets of congeneric ho...
Quantum mechanics (QM)-driven ¹Hiterative functionalized spin analysis produces HifSA profiles, which encode the complete ¹H spin parameters (“nuclear genotype”) of analytes of interest. HifSA profiles enable the establishment of digital reference standards (dRS) that are portable, FAIR (findable - accessible - interoperable - reusable), and fit fo...
Three unique linear oligomeric depsipeptides, designated as cavomycins A–C (1–3), were identified from Streptomyces cavourensis, a gut bacterium associated with the annelid Paraleonnates uschakovi. The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including m...
Flavan‐3‐ol monomers are the building blocks of proanthocyanidins (PACs), natural compounds from plants shown to mediate specific biologic activities on dentin. While the stereochemistry of the terminal flavan‐3‐ols, catechin (C) versus epicatechin (EC), impacts the biomechanical properties of the dentin matrix treated with oligomeric PACs, structu...
In botanical extracts, highly abundant constituents can mask or dilute the effects of other and often more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredien...
Breast cancer risk continues to increase post menopause. Anti-estrogen therapies are available to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer prevention. Natural products such as hops (Humulus lupulus) and three pharmacopeial licorice (Glycyrrhiza)...
CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whe...
Monoterpenoids are integral to the chemical composition of the widely used adaptogenic dietary supplement Rhodiola rosea. The present study expands the chemical space and stereochemical information about these taxon-specific constituents from the isolation and characterization of five geraniol-derived glucosides, 1-5. While 1 and 2 exhibited almost...
Monoclonal antibody-drug conjugates (ADCs) are an expanding therapeutic class of biomolecules for which relatively few analytical and preparative separation options exist. Purification of ADCs with a specific drug antibody ratio is even more challenging. We report the first application of countercurrent separation (CCS) to this problem. An ADC mimi...
Investigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric seco B-type procyanidin derivatives, 1-5. This includes scalemic mixtures of gambiriin A1 (1a) and A2 (2a) and their newly described optical antipodes, ent-gambiriin A1 (1b) and ent-gambiriin A2 (2b), respectively,...
Licorice, the roots and rhizomes of Glycyrrhiza glabra L., has been used as a medicinal herb, herbal adjuvant, and flavoring agent since ancient times. Recently, licorice extracts have become popular as dietary supplements used by females to alleviate menopausal symptoms. Exposure to licorice products containing high levels of glycyrrhizic acid can...
Four new rufomycins, compounds 1-4, named rufomycins 56, 57, 58, and 61, respectively, exhibiting new skeletal features, were obtained from Streptomyces atratus strain MJM3502 and were fully characterized. Compounds 1 and 2 possess a 4-imidazolidinone ring not previously encountered in this family of cyclopeptides, thereby resulting in a [5,17] bic...
Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges for data access, both within the discipline and for...
Aim:
Grape seed extract contains a complex mixture of proanthocyanidins (PACs), a plant biopolymer used as a biomaterial to improve reparative and preventive dental therapies. Co-polymerization of PACs with type I collagen mechanically reinforces the dentin extracellular matrix. This study assessed the biocompatibility of PACs from grape seed extr...
Breast cancer risk continues to rise post menopause. Endocrine therapies are employed to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer preventionatural products such as hops ( Humulus lupulus ) and pharmacopoeial licorice ( Glycyrrhiza ) species, whic...
The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake. Therefore, any instrumental method of analysis applicable to the impurity analysis should be able to detect and quantify the analytes at those levels. This investigation was designed...
Introduction: Breast cancer risk continues to rise following menopause, despite the cessation of ovarian estrogen synthesis. High risk women are often hesitant to take anti-endocrine therapies for breast cancer prevention. Therefore, alternative strategies with greater acceptability are needed. Popular botanicals for menopausal health such as licor...
To enable the further exploration of structure-activity relationships (SARs) of proanthocyanidins (PACs) with dentin biomodification abilities, Cinnamomum verum was selected for scaled-up purification of mixed A-/B-type, medium-size PAC oligomers. Sequential purification by centrifugal partition chromatography (CPC), Sephadex LH-20, and semiprep HP...
The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after...
Much confusion exists about the chemical composition of widely sold Cannabis sativa products that utilize the cannabidiol (CBD) acronym and related terms such as "CBD oil", "CBD plus hemp oil", "full spectrum CBD", "broad spectrum CBD", and "cannabinoids". Their rational chemical and subsequent biological assessment requires both knowledge of the c...
Flavonoids are a vast group of metabolites that are essential for vascular plant physiology and, thus, occur ubiquitously in plant-based/-derived foods. The solitary designation of thousands of known flavonoids hides the fact that their metabolomes are structurally highly diverse, consist of disparate subgroups, yet undergo a certain degree of meta...
With the recent explosion of information, Natural Products (NP) research critically needs efficient ways to access and share knowledge, also to save precious knowledge being lost [1]. The reporting and sharing of NP occurrences in biological organisms are relevant to numerous scientific fields ranging from drug discovery to chemical ecology or chem...
Rufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins...
An extract from Artemisia dracunculus L. (termed PMI-5011) improves glucose homeostasis by enhancing insulin action and reducing ectopic lipid accumulation, while increasing fat oxidation in skeletal muscle tissue in obese insulin resistant male mice. A chalcone, DMC-2, in PMI-5011 is the major bioactive that enhances insulin signaling and activati...
The goal of the qNMR Summit is to take stock of the status quo and the recent developments in qNMR research and applications in a timely and accurate manner. It provides a platform for both advanced and novice qNMR practitioners to receive a well-rounded update and discuss potential qNMR-related applications and collaborations. For over a decade, s...
Objective:
To elucidate the structure-activity relationships (SARs) of proanthocyanidins (PACs) with type I collagen using sixteen chemically defined PACs with degree of polymerization (DP) 2-6.
Methods:
Under a dentin model, the biomimicry of PACs with type I collagen was investigated by dynamic mechanical analysis (DMA) and infrared spectrosco...
Nontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4/5/6/7 (Rufomycin 4–7), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1/...
The importance of Trifolium pratense L. as a dietary supplement and its use in traditional medicine prompted the preparation of a thorough metabolite profile. This included the identification and quantitation of principal constituents as well as low abundant metabolites that constitute the residual complexity (RC) of T. pratense bioactives. The pur...
Classical 1D 1H NMR spectra are prototypic for NMR spectroscopy in that they represent a wealth of chemical information encoded into convoluted graphs or patterns that contain complex features (aka multiplets), even for seemingly simple molecules. Accordingly, the utility of NMR depends on the theoretical and visual skills required to extract all t...
Classical 1D 1H NMR spectra are prototypic for NMR spectroscopy in that they represent a wealth of chemical information encoded into convoluted graphs or patterns that contain complex features (aka multiplets), even for seemingly simple molecules. Accordingly, the utility of NMR depends on the theoretical and visual skills required to extract all t...
p>Introduction: our purpose was to define if licorice and its main bioactive compounds can suppress aromatase expression/activity and Nrf2 dependent detoxification pathways in the postmenopausal breast. This chemopreventive potential has not previously been reported in preclinical models of high-risk postmenopausal breast.
Methods: Inhibition of a...
Plant‐derived proanthocyanidins (PACs) mediate physicochemical modifications to the dentin extracellular matrix (ECM). The structure–activity relationships of PACs remain largely unknown, mostly due to the varied complex composition of crude extracts, as well as the challenges of purification and mechanistic assessment. To assess the role of galloy...
Prenyl moieties are commonly encountered in the natural products of terpenoid and mixed biosynthetic origin. The reactivity of unsaturated prenyl motifs is less recognized and shown here to affect the acyclic Rhodiola rosea monoterpene glycoside, kenposide A (8), which oxidizes readily on silica gel when exposed to air. The major degradation produc...
Two new diprenylated coumaric acid isomers (1a and 1b) and two known congeners, capillartemisin A (2) and B (3), were isolated from Artemisia scoparia as bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D...
Curcuma longa (turmeric) has an extensive history of ethnomedical use for common ailments, and "curcumin"-containing dietary supplements (CDS) are a highly visible portion of today's self-medication market. Owing to raw material cost pressure, CDS products are affected by economically motivated, nefarious adulteration with synthetic curcumin ("sync...
The rapid spread of COVID-19 underscores the need for new treatments. Here we report that cannabidiol (CBD), a compound produced by the cannabis plant, inhibits SARS-CoV-2 infection. CBD and its metabolite, 7-OH-CBD, but not congeneric cannabinoids, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after cellular infection, i...
Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges to data access, either within the discipline or to...
Favipiravir is an established antiviral currently assessed as an investigational drug for the treatment of COVID‐19. Favipiravir is strikingly similar to two molecules that WHO lists as essential medicines, which also consist of a six‐membered aromatic N‐heterocycle bearing a carboxamide function: the anti‐tuberculosis agent, pyrazinamide, and nico...
Optimal parameters for the auto-hydrolysis of (iso)flavone glycosides to aglycones in ground Trifolium pratense L. plant material were established as a “green” method for the production of a reproducible red clover extract (RCE). The process utilized 72-h fermentation in DI water at 25 and 37 °C. The aglycones obtained at 25 °C, as determined by UH...
The present study demonstrates the relationship between conventional and quantum mechanical (QM) NMR spectroscopic analyses, shown here to assist in building a convincingly orthogonal platform for the solution and documentation of demanding structures. Kaempferol-3-O-robinoside-7-O-glucoside, a bisdesmosidic flavonol triglycoside and botanical mark...
Introduction: Breast cancer risk continues to rise following menopause, despite the cessation of ovarian estrogen synthesis. Pathways involving increased aromatase activity and inflammation in the breast microenvironment are implicated. Their concerted disruption could be protective against breast cancer. Popular botanicals for menopausal health, s...
Quantitative 1H nuclear magnetic resonance (qHNMR) is a highly regarded analytical methodology for purity determination as it balances metrological rigor, practicality, and versatility well. While ideal for intrinsically mass-limited samples, external calibration (EC) qHNMR is overshadowed by the prevalence of internal calibration and perceived rat...
Purpose
Dentin endogenous proteases are involved in the progression of dental caries. This study investigated the proteolytic activity of endogenous enzymes of carious and sound dentin of primary teeth and the potential selective inhibitory effect of plant-derived proanthocyanidins (PACs).
Methods
Carious and sound dentin from forty extracted prim...
The seeds of the akuamma tree (Picralima nitida) have been used as a traditional treatment for pain and fever. Previous studies have attributed these effects to a series of indole alkaloids found within the seed extracts; however, these pharmacological studies were significantly limited in scope. Herein, an isolation protocol employing pH-zone-refi...
Objectives
To develop a protocol for assessment of the bulk viscoelastic behavior of dentin extracellular matrix (ECM), and to assess relationships between induced collagen cross-linking and viscoelasticity of the dentin ECM.
Methods
Dentin ECM was treated with agents to induce exogenous collagen cross-linking: proanthocyanidins (PACs) from Vitis...
Extracts of red clover (Trifolium pratense L.), containing estrogenic isoflavones like genistein and daidzein and the proestrogenic isoflavones formononetin and biochanin A, are used by women as dietary supplements for the management of menopausal symptoms. Although marketed as a safer alternative to hormone therapy, red clover isoflavones have bee...
Proanthocyanidins (PACs) are near-ubiquitous and chemically complex metabolites, prototypical of higher plants. Their roles in food/feed/nutrition and ethnomedicine are widely recognized but poorly understood. With the analysis of evidence that underlies this challenge, this perspective identifies shortcomings in capturing and delineating PAC struc...
The present study elucidated the structures of three A-type tri- and tetrameric proanthocyanidins (PACs) isolated from Cinnamomum verum bark to the level of absolute configuration and determined their dental bioactivity using two therapeutically relevant bioassays. After selecting a PAC oligomer fraction via a biologically diverse bioassay-guided p...
Curcuma longa (turmeric) has a long ethnomedical background for common ailments, and Dietary Supplements (DS) labelled as “Curcumin” (CDS) are a highly visible portion of today’s selfmedication market. Due to cost pressure, these CDS products are affected by economically motivated adulteration with synthetic curcumin and are associated with unexpec...
Curcuma longa (turmeric) has a long ethnomedical background for common ailments, and Dietary Supplements (DS) labelled as “Curcumin” (CDS) are a highly visible portion of today’s selfmedication market. Due to cost pressure, these CDS products are affected by economically motivated adulteration with synthetic curcumin and are associated with unexpec...
Botanical dietary supplements (BDS) containing hops are sold as women's health supplements due to the potent hop phytoestrogen, 8-prenylnaringenin (8-PN), and the cytoprotective chalcone, xanthohumol. Previous studies have shown a standardized hop extract to beneficially influence chemical estrogen carcinogenesis in vitro by fostering detoxified 2-...
p>The seeds of the akuamma tree ( Picralima nitida ) have been used as a traditional treatment for pain and fever. Previous studies have attributed these effects to a series of indole alkaloids found within the seed extracts; however, these pharmacological studies were significantly limited in scope. Herein, an isolation protocol employing pH-zone-...
Many botanicals used for women's health contain estrogenic (iso)flavonoids. The literature suggests that estrogen receptor beta (ERβ) activity can counterbalance estrogen receptor alpha (ERα)-mediated proliferation, thus providing a better safety profile. A structure-activity relationship study of (iso)flavonoids was conducted to identify ERβ-prefe...
In the last two decades, quantitative NMR (qNMR) has become increasingly important for the analysis of pharmaceuticals, chemicals, and natural products including dietary supplements. For the purpose of quality control and chemical standardization of a large variety of pharmaceutical, chemical, and medicinal products, qNMR has proven to be a valuabl...
Issues related to pharmaceutical quality are arising at an alarming rate. Pharmaceutical quality concerns both the Active Pharmaceutical Ingredients (APIs) and the Finished Drug Product/ Formulation. Recently, there has been a significant increase in the number of reports of harmful impurities in marketed drug formulations. Impurities range from so...
This Miniperspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labelled health products, and associated health claims, lack a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other “natural” panaceas, where valid et...
An investigation of the dental bioactive proanthocyanidin (PAC) oligomer fractions led to three structurally distinct new PACs (1-3) from pine bark. Pinutwindoublin (1) is the first reported trimer with double A-type interflavanyl linkages (2α→O→5,4α→6 and 2α→O→7,4α→8). Pinuspirotetrin (2) represents the first reported PAC tetramer with a heterodim...
The ¹H NMR spectra of crude extracts from a total of 33 Actaea samples were acquired and analyzed for their species- and plant part-specific metabolomic characteristics by identifying fingerprint resonances via visual observation as well as a chemometric approach using principal component analysis (PCA). The main study subjects were the roots/rhizo...
Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2 and 4-6), seven trimers (10-16), and six tetramers (17-22). New...
NMR- and MS-guided metabolomic mining for new phytoconstituents from a widely used dietary supplement, Rhodiola rosea, yielded two new (+)-myrtenol glycosides, 1 and 2, and two new cuminol glycosides, 3 and 4, along with three known analogues, 5-7. The structures of the new compounds were determined by extensive spectroscopic data analysis. Quantum...
Chlorophylls are present in all extracts from the aerial parts of green plant materials. Chlorophylls may act as in vitro bioassay nuisance compounds, possibly preventing the reproducibility and accurate measurement of readouts due to their UV/vis absorbance, fluorescence properties, and tendency to precipitate in aqueous media. Despite the diversi...
div>Isolation of underivatized PACs led to three new, structurally unique PACs ( 1 - 3 ) from pine bark. Pinutwindoublin ( 1 ) is the first known trimer with double A-type interflavanyl linkages (2α→O→5,4α→6 and 2α→O→7,4α). Pinuspirotetrin ( 2 ) represents the first PAC tetramer with a heterodimeric framework consisting of one spiro-type and one A-...
The biological processes related to protein homeostasis in Mycobacterium tuberculosis, the etiologic agent of tuberculosis, have recently been established as critical pathways for therapeutic intervention. Proteins of particular interest are ClpC1 and the ClpC1–ClpP1–ClpP2 proteasome complex. The structure of the potent antituberculosis macrocyclic...
Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2, 4–6), seven trimers (10–16), and six tetramers (17–22). New out...
Botanical dietary supplements produced from hops (Humulus lupulus) containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Due to the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated a...
Objectives
Proanthocyanidins (PACs) are biocompounds mimicking native collagen cross-links. The effective and practical delivery of any biocompound is pivotal for clinical usage. The aim was to investigate the dentin biomodification and effective formation of dentin-resin biointerfaces of two highly bioactive PAC-rich extracts, Vitis vinifera Vv an...
In the 1930s, it was discovered that the ability of synthetic Vitamin C to treat scurvy was inferior to plant extracts containing Vitamin C. This observation led to the proposal of Vitamin P (permeability), as an essential phytochemical dietary nutrient. Subsequent attempts to isolate and characterize Vitamin P led to confusing and sometimes irrepr...
NMR- and MS-guided metabolomic mining for new phytoconstituents from a widely used dietary supplement, Rhodiola rosea , yielded two new (+)-myrtenol glycosides, 1 and 2 , and two new cuminol glycosides ( 3 and 4 ), along with three known analogues ( 5 – 7 ). The structures of the new compounds were determined by extensive spectroscopic analysis. Qu...
Utilizing the distinct HMBC crossed-peak patterns of lower-field range (LFR; 11.80‒14.20 ppm) hydroxyl singlets, presented NMR methodology characterizes flavonoid metabolomes both qualitatively and quantitatively. It enables simultaneous classification of the structural types of 5-OH flavonoids and biogenetically related 2'-OH chalcones, as well as...
This study represents a systematic chemical and biological study of the rufomycin (RUF) class of cyclic heptapeptides, which our anti-TB drug discovery efforts have identified as potentially promising anti-TB agents that newly target the caseinolytic protein C1, ClpC1. Eight new RUF analogues, rufomycins NBZ1–NBZ8 (1–8), as well as five known pepti...
Quantitative correlations between the contents of the flavonolignans silychristin A and silybins A/B provide biosynthetic clues that support a pathway in which one mesomeric form of a taxifolin radical is undergoing an oxidative coupling with a coniferyl alcohol radical. The flavonolignan content and patterns reported in the literature for 53 sampl...
A dentin biomodification strategy with selective proanthocyanidin (PAC)-enriched extracts reinforces dentin and dentin-resin interfaces. Enrichment of the extracts according to the degree of polymerization allows exploration of bioactive principles of PACs and structure-activity relationships. This study investigated the sustained dentin matrix bio...
While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and requi...
Complementing classical drug discovery, phytochemicals act on multiple pharmacological targets, especially in botanical extracts, where they form complex bioactive mixtures. The reductionist approach used in bioactivity-guided fractionation to identify single bioactive phytochemicals is inadequate for capturing the full therapeutic potential of the...
The cycloartane triterpene content in the roots/rhizomes (RR) and aerial parts (PX) of Actaea racemosa (AR), A. podocarpa (AP), and A. cordifolia (AC) have been investigated by quantitative 1H NMR (qHNMR). Thereby, it was demonstrated that qHNMR represents a powerful methodology for the analysis of crude plant extracts as it does not rely on the ra...