Metabolism of natural and synthetic bioactive compounds in Cunninghamella fungi and their applications in drug discovery.

Investigation of xenobiotic metabolism is a key step for drug discovery. Since the in vivo investigations may be associated with harmful effects attributed to production of toxic metabolites, it is deemed necessary to predict their structure especially at the preliminary clinical studies. Furthermore, the application of microorganisms that are capable of metabolizing drugs mimic human metabolism and consequently may predict possible metabolites.

Papaverinol--Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening.

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico.

Biotransformation of Modified Benzylisoquinoline Alkaloids: Boldine and Berberine and In Silico Molecular Docking Studies of Metabolites on Telomerase and Human Protein Tyrosine Phosphatase 1B.

Natural nitrogen heterocycles biotransformation has been extensively used to prepare synthetic drugs and explore the fate of therapeutic agents inside the body. Herein, the ability of filamentous fungi to biotransform boldine and berberine was investigated. Docking simulation studies of boldine, berberine and their metabolites on the target enzymes: telomerase (TERT) and human protein tyrosine phosphatase 1B (PTP-1B) were also performed to investigate the anticancer and antidiabetic potentials of compounds .

New adipate esters from : isolation, identification, biosynthesis and prediction of potential opioid/anti-opioid and antidiabetic activities.

Metabolites of the fungus NRRL 1382 were investigated under the effect of fusidic acid () feeding. In addition to ergosterol () which is a fungal sterol, two novel adipate esters () were isolated, and their structures were fully investigated using various spectroscopic analyses, including 1 D, 2 D NMR and HRESIMS. biological target prediction and molecular docking investigation revealed a potential agonist/antagonist activity for compound by binding to µ opioid receptor and antidiabetic effect by aldose reductase inhibitory activity for compound .

Microbial transformation of some simple isoquinoline and benzylisoquinoline alkaloids and in vitro studies of their metabolites.

Simple isoquinoline alkaloids (heliamine, dehydroheliamine), a phthalide isoquinoline alkaloid noscapine, and an aporphine alkaloid boldine are biosynthetically derived from an amino acid tyrosine. These substrates and a simple synthetic isoquinoline alkaloid (2-acetyl-7-amino-1,2,3,4-tetrahydroisoquinoline) contain an isoquinoline nucleus. The biotransformation of these substrates via reduction, oxidation, hydroxylation, and N-oxidation reactions with different microorganism produced nine metabolites, namely: N-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl) acetamide (Metabolite 1), heliamine N-oxide (Metabolite 2), 6,7-dimethoxyisoquinoline (Metabolite 3), 3,4-dihydro-6,7-dimethoxy isoquinolin-1-one (Metabolite 4), heliamine (Metabolite 5), dehydroheliamine N-oxide (Metabolite 6), cotarnine (Metabolite 7), 5-hydroxy cotarnine (Metabolite 8), and boldine N-oxide (Metabolite 9).

Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a.

The metabolism of papaverine, the opium benzylisoquinoline alkaloid, with Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968 and Cunninghamella echinulate ATCC 1382 has resulted in O-demethylation, O-methylglucosylation and N-oxidation products. Two new metabolites (4″-O-methyl-β-D-glucopyranosyl) 4'-demethyl papaverine and (4″-O-methyl-β-D-glucopyranosyl) 6-demethyl papaverine, (Metabolites 5 and 6) together with 4'-O-demethylated papaverine (Metabolite 1), 3'-O-demethylated papaverine (Metabolite 2), 6-O-demethylated papaverine (Metabolite 3) and papaverine N-oxide (Metabolite 4) were isolated. The structure elucidation of the metabolites was based primarily on 1D, 2D-NMR analyses and HRMS.

Fucoidan Characterization: Determination of Purity and Physicochemical and Chemical Properties.

Fucoidans are marine sulfated biopolysaccharides that have heterogenous and complicated chemical structures. Various sugar monomers, glycosidic linkages, molecular masses, branching sites, and sulfate ester pattern and content are involved within their backbones. Additionally, sources, downstream processes, and geographical and seasonal factors show potential effects on fucoidan structural characteristics.

Cloning and Overexpression of Strictosidine β-D-Glucosidase Gene Short Sequence from in .

Strictosidine-β-D-glucosidase (SGD) is considered as a key enzyme in the production of bisindole alkaloids in . The present study illustrated the production of a short sequence of this enzyme in without codon optimization. Strictosidine-β-D-glucosidase () gene short sequence (1434 bp), which lacks the conserved sequence KGFFVWS and the localization peptide sequence at the C-terminal, was amplified from cDNA of leaves, cloned and expressed in .

Microbial Oxidation of the Fusidic Acid Side Chain by .

Biotransformation of fusidic acid () was accomplished using a battery of microorganisms including NRRL 1382, which converted fusidic acid () into three new metabolites ⁻ and the known metabolite . These metabolites were identified using 1D and 2D NMR and HRESI-FTMS data. Structural assignment of the compounds was supported via computation of ¹H- and C-NMR chemical shifts.

Antioxidant effect of flavonoids on DCF production in HL-60 cells.

A fluorometric microplate assay was performed for the detection of respiratory burst activity in a human leukaemia cell line HL-60 by assessing oxidation of 2',7'-dichloro fluorescin diacetate (DCFH-DA). This method is based on the detection of DCFH oxidation due to the presence of hydrogen peroxide. In the present study, the antioxidant activity of a number of structurally related flavonoids of plant origin and some of their microbial transformation products (1-18) were evaluated.