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Publications (130)
Research progress from mainly over the last five years is described for a multidisciplinary collaborative program project directed toward the discovery of potential anticancer agents from a broad range of taxonomically defined organisms. Selected lead compounds with potential as new antitumor agents that are representative of considerable structura...
The known solid-tumor-selective cytotoxin aulosirazole (1) was identified from bioactive extracts from the culture medium of the cyanobacterium Nostoc sp. UIC 10771. Here, we demonstrate that 1 induces the nuclear accumulation of FOXO3a in OVCAR3 using both Western blot analysis and immunofluorescence confocal microscopy. We also report the discove...
A new linear lipopeptide, phormidepistatin (1), containing an epi-statine amino acid was isolated from cf. Phormidium sp. strain UIC 10484. The planar structure was elucidated by 1D and 2D NMR experimentation. The relative configuration was determined by J-based configurational analysis and the absolute configuration by advanced Marfey's analysis....
Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. Pseudovibrio bacteria have attracted attention because they are part of the microbiome of healthy marine sponges. Two-thirds of Pseudovibrio genomes contain a member of a nonribosomal peptide synthetase-polyketide s...
Pseudovibrio are α-proteobacteria proposed to contribute to marine sponge health. Lack of reverse genetics have hindered exploration of the ecological and biotechnological potential of Pseudovibrio. Here we describe reverse genetics methods that enabled identification of 12 pseudovibriamides, which we show affect motility and biofilm behavior of Ps...
Collective behavior is a common feature of life. Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. We have identified a link between motility/biofilms and a nonribosomal peptide synthetase-polyketide synthase gene cluster family ( ppp ) conserved in Pseudovibrio an...
Two laxaphycin type-B cyclic dodecapeptides, laxaphycins B5 and B6, were obtained from UIC 10484, a freshwater cf. Phormidium sp. Analysis using the 16S rRNA sequence found UIC 10484 to clade with UIC 10045, a known laxaphycin type-A and -B producer, and MS/MS analysis revealed the presence of two novel laxaphycin type-B compounds. The structures o...
Stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by Stig cyclases through a three‐step cascade involving Cope rearrangement, 6‐exo‐trig cyclization, and a final electrophilic aromatic substitution. Reported here is a comprehensive study of all currently annotated Stig cyclases, revealing that these proteins...
Stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by Stig cyclases through a three‐step cascade involving Cope rearrangement, 6‐exo‐trig cyclization, and a final electrophilic aromatic substitution. Reported here is a comprehensive study of all currently annotated Stig cyclases, revealing that these proteins...
Cyanobactins are a large family of cyanobacterial ribosomally synthesized and post‐translationally modified peptides (RiPPs) often associated with biological activities, such as cytotoxicity, antiviral, and antimalarial activities. They are traditionally described as cyclic molecules containing heterocyclized amino acids. However, this definition h...
p>The stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by the Stig cyclases through a three-step cascade involving Cope rearrangement, 6- exo -trig cyclization and a final electrophilic aromatic substitution. Here we report a comprehensive study of all currently annotated Stig cyclases, and reveal that these...
Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested whether F. prausnitzii and other gut abundant bacteria...
Background. Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. We recently reported a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients. Methods. To determine whether F. prausnitzii and other gut abundant...
Cyanobacteria are a source of chemically diverse metabolites with potential medicinal and biotechnological applications. Rapid identification of compounds is central to expedite the natural product discovery process. Mass spectrometry has been shown to be an important tool for dereplication of complex natural product samples. In addition, chromatog...
Actinomycete bacteria isolated from freshwater environments are an unexplored source of natural products. Here we report the complete genome of the Great Lakes-derived Micromonospora sp. strain B006, revealing its potential for natural product biosynthesis. The 7-megabase pair chromosome of strain B006 was sequenced using Illumina and Oxford Nanopo...
Background:
Prostate cancer presents the highest incidence rates among all cancers in men. Hapalindole H (Hap H), isolated from Fischerella muscicola (UTEX strain number LB1829) as part of our natural product anticancer drug discovery program, was found to be significantly active against prostate cancer cells.
Materials and methods:
In this stud...
The human 20S proteasome inhibitor scytonemide A (1), a macrocyclic imine originally isolated from the cyanobacterium Scytonema hofmanni, was synthesized via a biomimetic solid-phase peptide synthesis (SPPS) approach employing the Weinreb AM resin. Utilizing this approach, cyclization of the protected heptapeptide via formation of the imine bond oc...
Cultured cyanobacteria produce secondary metabolites with a wide range of biological activities and are an important source of natural products. In the context of secondary metabolite discovery, microbial culture conditions are expected to support optimum growth, induce maximum chemical diversity, and be suitable for the majority of cyanobacterial...
The cell extracts of two cultured freshwater Nostoc spp., UIC 10279 and UIC 10366, both from the suburbs of Chicago, showed antiproliferative activity against MDA-MB-231 and MDA-MB-435 cancer cell lines. Bioassay-guided fractionation led to the isolation of five glycosylated cylindrocyclophanes, named ribocyclophanes A–E (1–5) and cylindrocyclophan...
Annual Meeting of the American Society of Pharmacognosy
Merocyclophanes C and D (1 and 2) were isolated from the cell extract of the cultured cyanobacterium UIC 10110. The structures were determined by one-dimensional nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry and confirmed by 2D NMR techniques. The absolute configurations were determined using electro...
Cultured cyanobacteria are an important source of natural products for drug discovery as many of them produce secondary metabolites with therapeutically relevant activities. For the purpose of drug discovery, culture conditions must provide optimum growth and maximum diversity of secondary metabolites. To investigate the effect of culture media on...
Recent progress is described in an ongoing collaborative multidisciplinary research project directed towards the purification, structural characterization, chemical modification, and biological evaluation of new potential natural product anticancer agents obtained from a diverse group of organisms, comprising tropical plants, aquatic and terrestria...
Next-generation sequencing (NGS) of 16S amplicon libraries has become a standard technique to investigate host-associated and environmental microbial communities. The informatics workflow for this technique involves a number of computational steps which typically include sequence pre-processing, operational taxonomic unit (OTU) clustering, and taxo...
Microseiramide (1), a cyclic heptapeptide, was isolated from a sample of the freshwater cyanobacterium Microseira sp. UIC 10445 collected in a shallow lake in Northern Indiana. Taxonomic identification of UIC 10445 was performed by a combination of morphological and phylogenetic characterization. Phylogenetic analysis revealed that UIC 10445 was a...
We have investigated and compared a number of sample conditions on different NMR platforms in the search of maximum SNR and optimal experiment time efficiency for structure elucidation and quantitation of natural products. Using restricted volume 3 mm Shigemi microcell assembly in conjunction with a 900 MHz NMR spectrometer equipped with a 5 mm car...
Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D N...
Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses in...
Abstract Two new (1 and 2) and three known (3–5) carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium Nostoc sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS...
The present study demonstrates the importance of adequate precision when reporting the delta and J parameters of frequency domain H-1 NMR (HNMR) data. Using a variety of structural dasses (terpenoids, phenolics, alkaloids) from different taxa (plants, cyanobacteria), this study develops rationales that explain the importance of enhanced precision i...
The present study was a collaborative research project with the Q'eqchi Maya of Livingston, Izabal, to explore the influence of sociocultural factors on the health and well-being of Q'eqchi women and the role of plant medicines in treating women's health conditions. Data were obtained through participant observation, semi-structured interviews, foc...
The hollow fiber assay (HFA) is a drug discovery tool to aid investigators in the prioritization of lead compounds identified by in vitro testing for further development in animal models of disease. In the HFA, cells are cultured in hollow fibers containing pores of a diameter (500 kDa) large enough for proteins and other macromolecules to enter, b...
The extract of UIC 10035, a strain obtained from a sample collected near the town of Homestead, South Florida, showed antiproliferative activity against MDA-MB-435 cells. Bioassay-guided fractionation led to the isolation of a series of cyclic lipodecapeptides, named minutissamides E-L (1-8). The planar structures were determined by analysis of HRE...
A collaborative project has been undertaken to explore filamentous fungi, cyanobacteria, and tropical plants for anti-cancer drug leads. Through principal component analysis, the chemical space covered by compounds isolated and characterized from these three sources over the last four years was compared to each other and to the chemical space of se...
Sanctolide A (1), a 14-membered polyketide-nonribosomal peptide (PK-NRP) hybrid macrolide, was isolated from the cultured cyanobacterium Oscillatoria sancta (SAG 74.79). The planar structure was determined using various spectroscopic techniques including HRESIMS, and 1D and 2D NMR analyses. The relative configuration was assigned by J-based configu...
Chemical investigation of two cultured cyanobacteria, Westiellopsis sp. (SAG strain number 20.93) and Fischerella muscicola (UTEX strain number LB1829) led to the isolation of three hapalindole-type alkaloids, namely hapalindole X (1), deschloro hapalindole I (2), and 13-hydroxy dechlorofontonamide (3), along with ten known indole alkaloids (hapali...
The cell extract of a cultured terrestrial Nostoc sp. (UIC 10062), obtained from a sample collected at Grand Mere State Park in Michigan, displayed antiproliferative activity against the HT-29 human colon cancer cell line. Bioactivity-guided fractionation of the cell extract, combined with LC-MS analysis, led to the isolation of two cyclophanes, na...
Chemical investigation of the cultured cyanobacterium Fischerella sp. (SAG strain number 46.79) led to the isolation of four nitrile-containing indole alkaloids, namely 12-epi-fischerindole I nitrile (1), deschloro 12-epi-fischerindole I nitrile (2), 12-epi-fischerindole W nitrile (3), and deschloro 12-epi-fischerindole W nitrile (4) along with a k...
Stigonemapeptin (1), a depsipeptide containing an Ahp (3-amino-6-hydroxy-2-piperidone) residue, was isolated from a bloom sample of the freshwater cyanobacterium Stigonema sp. collected from North Nokomis Lake in the Highland Lake District of northern Wisconsin. The planar structure was determined by 1D and 2D NMR experiments as well as HRESIMS ana...
Two anabaenopeptin-type peptides, lyngbyaureidamides A and B, together with two previously reported peptides lyngbyazothrins C and D, were isolated from the cultured freshwater cyanobacterium Lyngbya sp. (SAG 36.91). Their structures were determined by spectroscopic and chemical methods. Lyngbyazothrins C and D were also able to inhibit the 20S pro...
Four cyclic decapeptides, minutissamides A-D (1-4), were isolated from the cultured cyanobacterium Anabaena minutissima (UTEX 1613). The planar structures were determined using various spectroscopic techniques including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the α-amino acid residues were assigned using Marfey's metho...
Cyanobacteria are considered a promising source for new pharmaceutical lead compounds and a large number of chemically diverse and bioactive metabolites have been obtained from cyanobacteria over the last few decades. This review highlights the structural diversity of natural products from freshwater and terrestrial cyanobacteria. The review is div...
A software package, termed "CYANOS", has been developed to facilitate the data management and mining for natural product drug discovery efforts. This system allows for the management of data associated with field collections, culture conditions, harvests, extractions, chemical separations, and biological evaluation. This software utilizes a MySQL d...
Aspilia pruliseta Schweinf. (Asteraceae) is a medicinal plant indigenous to Uganda and the neighboring countries of East Africa. It has been used extensively by the rural population for the treatment of fevers and malaria. During the antimalarial evaluation of this plant, four nontoxic diterpenes were isolated that possessed moderate activity again...
Two cyclic peptides, scytonemides A (1) and B (2), were isolated from the cultured fresh water cyanobacterium Scytonema hofmannii (UTEX 1834) by bioassay-guided fractionation using a proteasome inhibition assay. The planar structures of the compounds were determined by a combination of MS and 1D and 2D NMR spectroscopy. The advanced Marfey's method...
Four hapalindole-related alkaloids, namely fischambiguines A and B, ambiguine P, ambiguine Q nitrile as well as ambiguine G nitrile were identified from the cultured cyanobacterium Fischerella ambigua (UTEX 1903). The structures were determined by spectroscopic analysis including MS, 1D and 2D NMR and X-ray crystallography. The alkaloids possessed...
Material collected from a parkway in the city of Chicago afforded the isolation of a Nostoc species (UIC 10022A). The extract of this strain displayed significant inhibition of the 20S proteasome as well as antiproliferative activity against HT29, MCF7, NCI-H460, and SF268 cancer cell lines. A standardized dereplication protocol allowed for the rap...
Eucapsitrione (1), an anthraquinone derivative with an indeno-anthracene- trione skeleton, was isolated from the cyanobacterium Eucapsis sp. (UTEX 1519) by bioassay-guided fractionation. The chemical structure was determined by analyzing MS and 1D and 2D NMR spectroscopic data. Eucapsitrione (1) showed anti-Mycobacterium tuberculosis activity in th...
Two polyketide metabolites, nhatrangins A (1) and B (2), were isolated from a Vietnamese collection of Lyngbya majuscula. These compounds are related to the aplysiatoxin series of metabolites, which have also been isolated from this species of marine cyanobacterium. The use of 900 MHz cryoprobe NMR allowed the elucidation of the 2D structure of 1 f...
Our previous work has demonstrated that several plants in the Piperaceae family are commonly used by the Q'eqchi Maya of Livingston, Guatemala to treat amenorrhea, dysmenorrhea, and pain. Extracts of Piper hispidum Swingle (Piperaceae), bound to the estrogen (ER) and serotonin (5-HT7) receptors.
To investigate the estrogenic and serotonergic activi...
Scytoscalarol (1), a antimicrobial sesterterpene bearing a guanidino group, was isolated from the cultured cyanobacterium Scytonema sp. (UTEX 1163) by bioassay-guided fractionation. The chemical structure was determined by spectroscopic analysis including MS and 1D and 2D NMR. Scytoscalarol (1) showed antimicrobial activities against Bacillus anthr...
Indolo[2,3-a]carbazole based inhibitors were synthesized from readily available indigo via a seven-step linear synthetic sequence with a moderate overall yield. The inhibitors were selectively and readily functionalized at the nitrogen on the indole portion of the carbazole unit. The synthesized analogs displayed moderate inhibitory activities towa...
Introduction Inhibition of the proteasome has been shown to be an effective cancer treatment with the FDA approval of Bortezomib (Velcade™) and clinical trials of Salinosporamide A. 1,2 In preliminary studies, the extract of a Nostoc sp. (UIC 10022A), collected in Chicago, Illinois, revealed significant proteasome inhibitory activity. The use of a...
Five new antibacterial ambiguine K-O isonitriles (1-5) and eight previously described indole alkaloids were isolated from the cultured cyanobacterium Fischerella ambigua (UTEX 1903) by bioassay-guided fractionation. The planar structures of the new compounds were determined by spectroscopic analysis including MS and 1D and 2D NMR. X-ray crystallogr...
A collaborative multidisciplinary research project is described in which new natural product anticancer drug leads are obtained from a diverse group of organisms, constituted by tropical plants, aquatic cyanobacteria, and filamentous fungi. Information is provided on how these organisms are collected and processed. The types of bioassays are indica...
A culture collection of cyanobacteria has been established at the University of Illinois at Chicago. This collection includes marine, terrestrial, and freshwater strains and contains representatives of the five orders of cyanobacteria: Chroococcales, Pleurocapsales, Oscillatoriales, Nostocales, and Stigonematales. In this study, extracts from a sub...
An LC-MS-NMR platform is demonstrated, which combines two innovations in microscale analysis, nanoSplitter LC-MS and microdroplet NMR, for the identification of unknown compounds found at low concentrations in complex sample matrixes as frequently encountered in metabolomics or natural products discovery. The nanoSplitter provides the high sensitiv...
Cyanobacteria, blue-green algae, are a rich source of bioactive secondary metabolites with many potential applications. The ubiquitin-proteasome proteolytic system plays an important role in selective protein degradation and regulates cellular events including apoptosis. Cancer cells are more sensitive to the proapoptotic effects of proteasome inhi...
A total of 86 lipophilic and hydrophilic extracts obtained from 43 samples of cultured and field collected freshwater and terrestrial cyanobacteria have been screened for their biological activities. Anti-microbial evaluation demonstrated 16.3% to be active against Gram-positive and 5.8% against Gram-negative bacteria, while 10.5% possessed antifun...
Many developing countries have restricted access and use of prescription drugs to treat common health conditions. In Guatemala, for example, it is estimated that between 65-80% of the people use traditional, complementary or alternative medicines as part of their primary health care. In terms of women's health, many of these plant-based medicines h...
Microorganisms comprise the bulk of biodiversity, but only a small fraction of this diversity grows on artificial media. This phenomenon was noticed almost a century ago, repeatedly confirmed, and termed the "great plate count anomaly." Advances in microbial cultivation improved microbial recovery but failed to explain why most microbial species do...