Leptochelins A-C, Cytotoxic Metallophores Produced by Geographically Dispersed Leptothoe Strains of Marine Cyanobacteria.

Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus Leptothoe. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three Leptothoe strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.

Assessment of Patients' Knowledge in Managing Side Effects of Chemotherapy: Case of King Abdul-Aziz University Hospital.

Patients education about chemotherapy and its side effects is important. The health-related distress among the patients can be decreased by promoting self-care behaviors. A cross-sectional study was conducted at the King Abdul-Aziz University Hospital with 90 patients from the hospital's oncology department in Jeddah during the period between December 2015 and January 2016. The study was performed by using a self-administered questionnaire among the sample of the study. Eight percent (n = 33) patients scored higher knowledge regarding chemotherapy and its side effects, while 11.1% (n = 8) had low knowledge. Moreover, 36.1% (n = 26) of patients reported complete compliance with the self-care behaviors to manage chemotherapy side effects, 43.1% (n = 31) reported partial compliance, and 20.8% (n = 15) reported less compliance. Physicians were reported as main source of information by 80.6% (n = 58) of their patients. Involving healthcare professionals in educating patients regarding chemotherapy can prove to have positive outcomes.

Level of physicians' awareness of antiepileptic drug adverse effects.

PURPOSE: The study aimed to investigate the level of physicians' awareness regarding the adverse effects of antiepileptic drugs (AEDs) that were reported by their patients and to investigate whether these adverse effects caused by AEDs were documented in patients' files. PRINCIPAL RESULTS: One hundred one patients and 21 physicians were recruited; one patient and 2 physicians did not take part in the study. Sixty-two percent of the patients had epileptic seizures for more than 3 years, and 74% of them had generalized seizures. Sodium valproate, carbamazepine, topiramate, vigabatrin, levetiracetam, and lamotrigine were the most frequently used AEDs by patients; whereas, phenytoin, clonazepam, and pregabalin were the least used. Drowsiness came on top on the adverse effects' list, where its occurrence was about twice the weight gain and almost three times as frequent as movement and behavioral adverse effects. CONCLUSION: Majority of the adverse effects were not documented in the patients' files. However, physicians were aware of majority of the adverse effects associated with AEDs.

Phenolics from Barleria cristata var. Alba as carcinogenesis blockers against menadione cytotoxicity through induction and protection of quinone reductase.

BACKGROUND: There are increasing interests in natural compounds for cancer chemoprevention. Blocking agents represent an important class of chemopreventive compounds. They prevent carcinogens from undergoing metabolic activation and thereby suppressing their interaction with cellular macromolecular targets. METHODS: The effect of phenolic compounds isolated from Barleria cristata var. alba as chemopreventive agent was evaluated. The ethyl acetate fraction of B. cristata was subjected to different chromatographic techniques for isolation of its major phenolic compounds. The isolated compounds were evaluated for their potential to induce the cancer chemopreventive enzyme marker NAD(P)H quinonereductase 1 (NQO1) in murine Hepa-1c1c7 cell model. RESULTS: The ethyl acetate fraction of B. cristata var. alba yielded five known compounds identified as verbascoside (1), isoverbascoside (2), dimethoxyverbascoside (3), p-hydroxy benzoic acid (4), and apigenin-7-O-glucoside (5). Among the tested compounds, isoverbascoside (2) was shown to potently induce the activity of the enzyme in a dose -dependent manner. As a functional assay for detoxification, compound 2 was the strongest to protect Hepa-1c1c7 against the toxicity of menadione, a quinone substrate for NQO1. CONCLUSION: This effect seemed to be attributed to the compound's potential to induce both the catalytic activity and protein expression of NQO1 as revealed by enzyme assay and Western blotting, respectively.

Biologically active compounds from the red sea sponge Suberea sp.

Investigation of the cytotoxic fraction of the extracts of the Red Sea sponge Suberea sp. resulted in the identification of two new compounds, 1-(hydroxy(1H-pyrrol-2-yl)methyl)guanidine and 4-(2-amino-3-methylbut-3-en-1-yl)phenol (1 and 2) together with the previously reported 2-(3,5-dibromo-4-hydroxyphenyl)acetamide (3), subereaphenol C (4), dibromoverongiaquinol (5) and bromochloroverongiaquinol (6). The compounds were assigned by assignment of their one- and two-dimensional NMR and MS spectral data. The cytotoxic activities of the compounds against two cancer cell lines were evaluated. In addition, the antimicrobial activities of the compounds was discussed.

Evaluation of the antiproliferative and cytotoxic activities of marine invertebrates-derived fungi.

The present study focuses on the evaluation of the cytotoxicity and antiproliferative activities of the organic extracts of 70 fungal strains associated with twelve Red Sea marine invertebrates. The fungal strains were obtained 10 sponges, one tunicate and one soft coral. Three different media including Sabouraud dextrose agar, malt extract agar and Czapek-Dox agar were used for the purification of the fungal isolates. The purified fungal isolates were cultured in their corresponding media (Sabouraud dextrose broth, Malt extract broth and Czapek-Dox broth) on shaker for 14 days at 26° C. After that, the cultures were lyophilized and the dried cultures were extracted with methanol. The methanolic extracts of these cultures were evaluated for their in vitro cytotoxicity and antiproliferative activities against three human cancer cell lines including breast adenocarcinoma (MCF-7), liver hepatocellular carcinoma (HepG2) and colorectal carcinoma (HCT-116). Nine extracts displayed potent and selective activity against MCF-7 with IC50 4.96-8.28µ g/mL without any significant effect on the other two cell lines. In addition, six extracts showed strong and selective activity against MCF-7 with IC50 11.37-15.53µ g/mL. On the other hand, most of the fungal extracts were inactive or weakly active against HepG2 and HCT-116.

Synthesis of Some 1,4,6-Trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles and Their Biological Evaluation as Cytotoxic and Antimicrobial Agents.

A series of novel 1,4,6-trisubstituted-2-oxo-1,2-dihydropyridine-3-carbonitriles supported with some functionalities reported to contribute to significant chemotherapeutic potential were synthesized and evaluated for their antimicrobial and/or cytotoxic activities. Thirteen compounds exhibited cytotoxic potential against a panel of three human tumor cell lines. Compounds 15, 23, and 24 proved to be the most active agents with a broad spectrum of cytotoxic activity. Analog 24 was considered as the most active cytotoxic agent, being 2.5 times more active than doxorubicin against the colon HT29 carcinoma cell line. Seventeen compounds were able to exert a variable antimicrobial profile, among which analogs 15, 20, 21, 23, and 24 were prominently active. The highest antimicrobial potential was displayed by analog 24, being equipotent to ampicillin against Staphylococcus aureus and Escherichia coli, together with a considerable antifungal activity comparable with clotrimazole. Collectively, compounds 15, 23, and 24 could be considered as possible dual antimicrobial-anticancer candidates.

Anabolic-androgenic steroids and dietary supplements among resistance trained individuals in western cities of Saudi Arabia.

BACKGROUND: Anabolic-androgenic steroids (AAS) contain testosterone-like androgens and are used as supplements to improve performance, therapeutic measures, appearance, and muscular development. PURPOSE: This study aimed to estimate using anabolic-androgenic steroids (AAS) and good and bad practices about dietary supplements among resistance-trained individuals. It further seeked to determine the use of common drugs and supplements containing anabolic steroids among resistance-trained individuals (who work out at the sports centre) and assess users' knowledge about its side effects. METHODS: A cross-sectional survey was conducted at the sports centres of the western cities of Saudi Arabia. A self-administered questionnaire was used to collect data from 120 male resistance-trained individuals. RESULTS: The majority of the participants (80%) reported that they had not used any hormonal bodybuilding supplement last year, while 20% said they had used such hormonal supplements. Approximately half (52.5%) of participants reported that they always used dietary supplements. A total of 44.2% of participants possessed inadequate knowledge of these products. The main reason behind the use of hormones and supplements was to increase muscle mass. CONCLUSIONS: A minority of resistance-trained individuals in the studied population frequently misused AAS. However, the results cannot be generalised to the whole of Saudi Arabia. AAS consumption can be reduced by enhancing the level of awareness and knowledge of potential adverse health outcomes.

New fatty acids from the Red Sea sponge Mycale euplectellioides.

Chemical investigation of the Red Sea sponge Mycale euplectellioides afforded two new compounds; hexacosa-(6Z,10Z)-dienoic acid methyl ester (1) and hexacosa-(6Z,10Z)-dienoic acid (2), along with two known compounds: icosa-(8Z,11Z)-dienoic acid methyl ester (3) and ß-sitosterol (4). The structures were elucidated by the interpretation of their spectral data. The total methanol extract (TME) of the sponge exhibited potent antimicrobial activity against the different strains at a concentration of 100 mg/mL. All tested fractions did not exhibit any activity against Serratia marcescens and tested fungal strains. The TME and different fractions displayed anti-inflammatory and antipyretic activities at doses of 100 and 200 mg/kg compared with indomethacin (8 mg). The TME exhibited a remarkable hepato-protective effect in CCl4-induced liver damage compared with silymarin. Furthermore, compounds 1 and 2 displayed weak activity against A549 non-small cell lung cancer, the U373 glioblastoma and the PC-3 prostate cancer cell lines.