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Metabolites of the fungus Cunninghamella echinulata NRRL 1382 were investigated under the effect of fusidic acid (1) feeding. In addition to ergosterol (2) which is a fungal sterol, two novel adipate esters (3, 4) were isolated, and their structures were fully investigated using various spectroscopic analyses, including 1 D, 2 D NMR and HRESIMS. In silico biological target prediction and molecular docking investigation revealed a potential agonist/antagonist activity for compound 3 by binding to µ opioid receptor and antidiabetic effect by aldose reductase inhibitory activity for compound 4. [ABSTRACT FROM AUTHOR]

Isoniazid is a synthetic antimicrobial and one of the most essential first-line drugs used in the treatment of tuberculosis. In addition, isoniazid has been used as a prophylactic drug for patients with latent Mycobacterium tuberculosis infection to prevent the reactivation of the disease. It is a prodrug that is activated by catalase-peroxidase (KatG) enzyme. Catalase peroxidase enzyme converts isoniazid to reactive species. Isoniazid reactive species inhibit enoyl acyl-carrier-protein reductase (InhA) enzyme, which is involved in the biosynthesis of fatty acids of mycobacteria. Isoniazid is metabolized by amidase enzyme into isonicotinic acid and hydrazine. Chronic toxicity of isoniazid results in hepatotoxicity and peripheral neuropathy. For active tuberculosis, isoniazid is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. Multiple extensively and totally drug-resistant strains of Mycobacterium tuberculosis were reported. Due to the development of Mycobacterium tuberculosis resistance to isoniazid, a continuous search for new drugs is a demand to combat this global problem. [ABSTRACT FROM AUTHOR]

Arecoline is a psychoactive alkaloid containing a reduced pyridine nucleus, isolated from Areca catechu L. (Arecaceae) with different biological activities on cardiovascular, digestive, nervous, and endocrine systems. Arecoline is the main toxic component of A. catechu responsible for oral carcinoma. It possesses a variety of pharmacological activities; it exhibits anticancer activity. It was reported that arecoline causes cytotoxicity through apoptosis in human endothelial cells. Moreover, the death of human leukemia K562 cells was induced by arecoline. Biotransformation is a structural modification of compounds such as amino acids, toxins, and drugs by enzymatic chemical reactions within living organisms. According to enzymatic sources, biotransformation is classified into three major types; microbial, plant cell culture, and animal cell culture transformation. It was suggested that microorganisms could be employed as a model of mammalian metabolism. Studying both mammalian and microbial transformation of arecoline is of interest by which we can reduce its toxicity, increase its bioavailability, and produce more active metabolites. [ABSTRACT FROM AUTHOR]

Genus Zamia is a diverse group of cycads belonging to the family Zamiaceae which includes most cycads. It is ranked as the second-largest genus of extant cycads in the new world. In contrast to other cycad species, Zamia species are trunkless, deciduous shrubs. The genus Zamia is by far the most ecologically varied, widely dispersed, and species-rich genus in the Americas. They are dioecious plants with male and female reproductive cones. Zamia plants are considered rich sources of numerous different natural metabolites, which may contribute to various biological activities such as cytotoxic, antimicrobial, antioxidant, and anti-inflammatory activities. These metabolites include flavonoids, biflavonoids, phenolic acids, volatile oils, and lignans that are considered the significant components of the phytochemical profile of Zamia. Zamia is a popular ornamental plant. It is also acknowledged as a therapeutic herb in both conventional and Western medicine. Various Zamia species have traditionally been used to treat a range of ailments by elderly locals in various locations. These ethnobotanical uses have led researchers to discover some valuable pharmacological properties of some Zamia species like cytotoxic, antiprotozoal, antioxidant, antimicrobial, and anti-Alzheimer activities. In this review, we have given an overview of different phytochemicals types present in Zamia species and their reported bioactivities in addition, the pharmacological, and ethnobotanical properties of certain Zamia species. [ABSTRACT FROM AUTHOR]

Cycadaceae is regarded as one of the largest cycad families. It is made up of 120 species of the single genus Cycas. Genus Cycas is found only in tropical and subtropical climates. They are dioecious plants with male and female reproductive cones. Members of Cycadaceae family are excellent suppliers of a wide range of beneficial phytochemicals however, only a few numbers of species had undergone phytochemical and pharmacological research. A wide battery of metabolites, including flavonoids, biflavonoids, phenolic acids, sterols, amino acids, lignans, and fatty acids, have been isolated and structurally identified from various Cycas species. Since biflavonoids are a defining trait of all cycads, we focused in this review on the various biflavonoids nuclei found in Cycadaceae and their distribution in distinct Cycas species among other isolated secondary metabolites. Therefore, we outlined the various biflavonoids nuclei found in Cycadaceae and their distribution in distinct Cycas species in this review. Additionally, we highlighted the diverse pharmacological effects of different Cycas species that their biflavonoid content can be credited with. [ABSTRACT FROM AUTHOR]

Biotransformation of isoniazid produced isonicotinic acid (1), isonicotinic acid N-oxide (2), and isonicotinamide (3) which were isolated by column chromatography using silica gel and Sephadex LH 20 and elucidated using various spectroscopies. This is the first report for isolation of 2. Antituberculosis activity was evaluated against Mycobacterium tuberculosis strains: drug sensitive (DS), multiple drug resistant (MDR) and extensively drug resistant (XDR). 1-3 and isoniazid showed MICs of 63.49, 0.22, 15.98 and 0.88 µM, respectively, against the DS strain. For the MDR strain, 2 and 3 exhibited MICs of 28.06 and > 1000 µM, respectively, while 1 was inactive. Moreover, 2 had an MIC of 56.19 µM against XDR strain, while 1 and 3 were inactive. Docking simulation using enoyl ACP reductase (InhA) revealed favorable protein-ligand interactions. In silico study of pharmacokinetics and hepatotoxicity predicted 1-3 to have good oral bioavailability and 2 to have a lower hepatoxicity probability than isoniazid. [ABSTRACT FROM AUTHOR]

Toxoplasmosis and cancer are life-threatening diseases with worldwide distribution. However, currently used chemosynthetic treatments are not devoid of their own intrinsic problems. Natural metabolites are gaining attention due to their lower side effects. In this study, we investigated for the first time Zamia floridana leaves extract and its different fractions for their toxoplasmocidal activity, using Virulent RH Toxoplasma gondii, and cytotoxic activity against MCF-7 and HCT-116 cancer cell lines using MTT assay. The n-butanol fraction was the most potent fraction against T. gondii with an EC50 of 7.16 ± 0.4 µg/mL compared to cotrimoxazole (4.18 ± 0.3 µg/mL). In addition, the n-BuOH fraction showed a significant cytotoxicity against MCF-7 and HCT-116 with IC50 of 12.33 ± 1.1 and 17.88 ± 1.4 µg/mL, respectively, compared to doxorubicin (4.17 ± 0.2 and 5.23 ± 0.3 µg/mL, respectively), with higher safety index against normal cell line (WISH). Therefore, the n-BuOH fraction was investigated for its phytochemicals using extensive chromatographic techniques, which led to the isolation of six compounds that were fully characterized using different spectroscopic techniques. Three biflavonoids (1, 2 and 4) in addition to two phenolic acid derivatives (3 and 5) and a flavonoid glycoside (6) were isolated. Compounds (1, 3, 5 and 6) were reported for the first time from Z. floridana. In silico docking studies for toxoplasmocidal and cytotoxic effects of these compounds revealed that compounds (1, 2, 4 and 6) have promising inhibition potential of either thymidylate synthase-dihydrofolate reductase (TS-DHFR) or cyclin dependent kinase 2 (CDK2) target proteins. This study is considered the first report of chemical and biological investigation of Z. floridana leaves. [ABSTRACT FROM AUTHOR]

Context: Some studies reported the chemical content and antimicrobial properties of Ocimum basilicum L. (Lamiaceae), relevant to the ecological variations in some areas of Egypt and other countries, yet no research was conducted on the plant cultivated in the central delta region of Egypt. Also, no previous data reported on inhibition of b-lactamases by O. basilicum. Objective: To assess b-lactamases inhibition by O. basilicum extracts and the individual constituents. Materials and methods: Dried aerial parts of O. basilicum were extracted by hydrodistillation for preparation of essential oil and by methanol for non-volatile constituents. Essential oil content and the methanol extract were analysed by GC-MS and UPLC-PDA-MS/MS, respectively. Methyl cinnamate was isolated and analysed by NMR. Broth microdilution method was used to investigate the antimicrobial against resistant clinical isolates of Escherichia coli identified by double disc synergy, combination disc tests and PCR. The most active oil content was further tested with a nitrocefin kit for b-lactamase inhibition and investigated by docking. Results: O. basilicum was found to contain methyl cinnamate as the major content of the essential oil. More interestingly, methyl cinnamate inhibited ESBL b-lactamases of the type CTX-M. The in vitro IC50 using nitrocefin kit was 11.6 mg/mL vs. 8.1 mg/mL for clavulanic acid as a standard b-lactamase inhibitor. Discussion and conclusions: This is the first study to report the inhibitory activity of O. basilicum oil and methyl cinnamate against b-lactamase-producing bacteria. The results indicate that methyl cinnamate could be a potential alternative for b-lactamase inhibition. [ABSTRACT FROM AUTHOR]

Biotransformation of fusidic acid (1) was accomplished using a battery of microorganisms including Cunninghamella echinulata NRRL 1382, which converted fusidic acid (1) into three new metabolites 2–4 and the known metabolite 5. 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 13C-NMR chemical shifts. Compounds 2 and 3 were assigned as the 27-hydroxy and 26-hydroxy derivatives of fusidic acid, respectively. Subsequent oxidation of 3 afforded aldehyde 4 and the dicarboxylic acid 5. Compounds 2, 4 and 5 were screened for antimicrobial activity against different Gram positive and negative bacteria, Mycobacterium smegmatis, M. intercellulare and Candida albicans. The compounds showed lower activity compared to fusidic acid against the tested strains. Molecular docking studies were carried out to assist the structural assignments and predict the binding modes of the metabolites. [ABSTRACT FROM AUTHOR]