Jihan M. Badr

Bioactive brominated metabolites from the red sea sponge Suberea mollis.

Reinvestigation of the Red Sea sponge Suberea mollis afforded two new bromotyrosine-derived alkaloids, subereamollines A (1) and B (2), two new brominated phenolic compounds, subereaphenols B (7) and C (9), and the known compounds aerothionin (3), homoaerothionin (4), 11,19-dideoxyfistularin-3 (5), aeroplysinin-1 (6), and aeroplysinin-2 (8). The structure determination of the isolated compounds was assigned using one- and two-dimensional NMR spectra and HRFABMS data. The antimicrobial and antioxidant activities of the isolated compounds have been evaluated. Aeroplysinin-1 displayed significant antimicrobial activity against S. aureus, P. aerugenosa, and K. pneumoniae. The isolated compounds were examined for their antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) solution-based chemical assay. Among the tested compounds, only subereaphenols B and C displayed a significant effect.

Theonellamide G, a potent antifungal and cytotoxic bicyclic glycopeptide from the Red Sea marine sponge Theonella swinhoei.

In our search for bioactive metabolites from marine organisms, we have investigated the polar fraction of the organic extract of the Red Sea sponge Theonella swinhoei. Successive chromatographic separations and final HPLC purification of the potent antifungal fraction afforded a new bicyclic glycopeptide, theonellamide G (1). The structure of the peptide was determined using extensive 1D and 2D NMR and high-resolution mass spectral determinations. The absolute configuration of theonellamide G was determined by chemical degradation and 2D NMR spectroscopy. Theonellamide G showed potent antifungal activity towards wild and amphotericin B-resistant strains of Candida albicans with IC50 of 4.49 and 2.0 μM, respectively. Additionally, it displayed cytotoxic activity against the human colon adenocarcinoma cell line (HCT-16) with IC50 of 6.0 μM. These findings provide further insight into the chemical diversity and biological activities of this class of compounds.

Brominated arginine-derived alkaloids from the red sea sponge Suberea mollis.

Investigation of a new collection of the Red Sea sponge Suberea mollis afforded two new brominated arginine-derived alkaloids, subereamines A (1) and B (2), a new brominated phenolic compound, subereaphenol D (3), and the known compounds dichloroverongiaquinol (4), aerothionin (5), and purealdin L (6). The structures of the isolated compounds were assigned using one- and two-dimensional NMR spectra and HRFABMS data. The absolute configurations of subereamines A (1) and B (2) were determined by acid hydrolysis followed by chiral-phase LC-MS. The antimicrobial and antioxidant activities of the isolated compounds have been evaluated. Dichloroverongiaquinol and subereaphenol D displayed significant antimicrobial activity. Using the DPPH TLC autographic rapid screen for free radical scavenging effects, subereaphenol D displayed a significant antioxidant effect. In addition, the cytotoxic activities of the isolated compounds were investigated.

Design and Optimization of Self-Nanoemulsifying Delivery System to Enhance Quercetin Hepatoprotective Activity in Paracetamol-Induced Hepatotoxicity

The present study aimed to develop optimized quercetin (QT)-loaded self-nanoemulsifying drug delivery system (SNEDDS) that offers protective effect against liver damage. Solubility study of QT in different oils, surfactants, and cosurfactants was performed. Ternary phase mixtures of the selected components were constructed to select a suitable range for each component. Experimental mixture design was utilized to optimize SNEDDSs that possess smaller globule size with enhanced emulsification and dissolution rates. QT SNEDDS was compared with QT suspension control and silymarin. In vivo evaluation and histopatholgical study of the selected QT SNEDDSs were achieved after administration of paracetamol over dosage to albino rats. Two optimized formulations were selected; one based on Sefsol and the other based on linoleic acid as an oily phase, Tween(®) 80 and polyethylene glycol 400 as surfactant and cosurfactant, respectively. Both Sefsol and linoleic-acid-optimized SNEDDS formulation showed no symptoms associated with toxicity and offered protective effect against paracetamol-induced hepatotoxicity by scavenging free radicals, attenuating lipid peroxidation, and enhancing the activity of antioxidants. The histopatholgical observations revealed that the inflammatory infiltrations induced by paracetamol were significantly ameliorated.

Bioactive Secondary Metabolites from the Red Sea Marine Verongid Sponge Suberea Species

In a continuation of our efforts to identify bioactive compounds from Red Sea Verongid sponges, the organic extract of the sponge Suberea species afforded seven compounds including two new dibrominated alkaloids, subereamollines C and D (1 and 2), together with the known compounds aerothionin (3), homoaerothionin (4), aeroplysinin-1 (5), aeroplysinin-2 (6) and a revised subereaphenol C (7) as ethyl 2-(2,4-dibromo-3,6-dihydroxyphenyl)acetate. The structures of the isolated compounds were assigned by different spectral data including optical rotations, 1D (1H and 13C) and 2D (COSY, multiplicity-edited HSQC, and HMBC) NMR and high-resolution mass spectroscopy. Aerothionin (3) and subereaphenol C (7) displayed potent cytotoxic activity against HeLa cell line with IC50 values of 29 and 13.3 µM, respectively. In addition, aeroplysinin-2 (6) showed potent antimigratory activity against the human breast cancer cell line MDA-MB-231 with IC50 of 18 µM. Subereamollines C and D are new congeners of the previously reported compounds subereamollines A and B with methyl ester functionalities on the side chain. These findings provide further insight into the biosynthetic capabilities of members of the genus Suberea and the chemical diversity as well as the biological activity of these compounds.

Bioactive 2(1H)-Pyrazinones and Diketopiperazine Alkaloids from a Tunicate-Derived Actinomycete Streptomyces sp.

As a part of our ongoing effort to allocate marine microbial bioactive leads, a tunicate-derived actinomycete, Streptomyces sp. Did-27, was investigated. Three new 2(1H)-pyrazinones derivatives, (S)-6-(sec-butyl)-3-isopropylpyrazin-2(1H)-one (1), (S)-3-(sec-butyl)-6-isopropylpyrazin-2(1H)-one (2) and (S)-6-(sec-butyl)-3-isobutylpyrazin-2(1H)-one (3), together with the known (1H)-pyrazinones analogues deoxymutaaspergillic acid (4), 3,6-diisobutyl-2(1H)-pyrazinone (5) and 3,6-di-sec-butyl-2(1H)-pyrazinone (6), and the diketopiperazine alkaloids cyclo(6-OH-d-Pro-l-Phe) (7), bacillusamide B (8), cyclo(l-Pro-l-Leu) and cyclo(l-Pro-l-Ile) (10) were isolated from this strain. The structures of the compounds were determined by study of their one- and two-dimensional NMR spectra as well as high-resolution mass spectral determinations. Compound 4 was reported previously as a synthetic product, while compound 6 was reported as 2-hydroxy-3,6-di-sec-butylpyrazine. Herein, we report the complete NMR data for compounds 4 and 6. The compounds were evaluated for their cytotoxic activities against three cell lines. Compound 5 showed potent and selective activity against HCT-116 cell line with IC50 of 1.5 μg/mL, while 1–10 showed variable cytotoxic activities against these cancer cell lines. These results provide further understanding about the chemistry and bioactivities of the alkylated 2(1H)-pyrazinone derivatives.

2,3-Seco-2,3-dioxo-lyngbyatoxin A from a Red Sea strain of the marine cyanobacterium Moorea producens

Chemical investigation of the organic extract of a Red Sea strain of the cyanobacterium Moorea producens has afforded 2,3-seco-2,3-dioxo-lyngbyatoxin A (1). Five known compounds including lyngbyatoxin A (2), majusculamides A and B (3 and 4), aplysiatoxin (5) and debromoaplysiatoxin (6) were also isolated. Their structures were elucidated by using HR-FAB-MS, 1D and 2D NMR analyses. The compounds were evaluated for antiproliferative activity against HeLa cancer cells. Lyngbyatoxin A (2) showed potent activity, with an IC50 of 9.2 nM, while 5 and 6 displayed modest activity with IC50 values of 13.3 and 3.03 μM, respectively. In contrast, compounds 1, 3 and 4 were inactive, with IC50 values greater than 50 μM. The lack of cytotoxicity for 2,3-seco-2,3-dioxo-lyngbyatoxin A (1) demonstrates that the indole moiety in lyngbyatoxin (2) is essential for its cytotoxicity, and suggests that detoxification of 2 may be carried out by biological oxidation of the indole moiety to yield 1.

Didemnaketals F and G, new bioactive spiroketals from a Red Sea ascidian Didemnum species

In continuation of our ongoing efforts to identify bioactive compounds from Red Sea marine organisms, a new collection of the ascidian Didemnum species was investigated. Chromatographic fractionation and HPLC purification of the CH2Cl2 fraction of an organic extract of the ascidian resulted in the identification of two new spiroketals, didemnaketals F (1) and G (2). The structure determination of the compounds was completed by extensive study of 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments in addition to high-resolution mass spectral data. Didemnaketal F (1) and G (2) differ from the previously reported compounds of this class by the lack the terminal methyl ester at C-1 and the methyl functionality at C-2. Instead, 1 and 2 possess a methyl ketone moiety instead of the terminal ester. Furthermore, didemnaketal F possesses a disubstituted double bond between C-2 and C-3, while the double bond was replaced by a secondary alcohol at C-3 in didemnaketal G. In addition, they possess the unique spiroketal/hemiketal functionality which was previously reported in didemnaketal E. Didemnaketals F (1) and G (2) displayed moderate activity against HeLa cells with of IC50s of 49.9 and 14.0 µM, respectively. In addition, didemnaketal F (1) displayed potent antimicrobial activity against E. coli and C. albicans. These findings provide further insight into the biosynthetic capabilities of this ascidian and the chemical diversity as well as the biological activity of this class of compounds.

A validated high performance thin layer chromatography method for determination of yohimbine hydrochloride in pharmaceutical preparations.

Background: Yohimbine is an indole alkaloid used as a promising therapy for erectile dysfunction. A number of methods were reported for the analysis of yohimbine in the bark or in pharmaceutical preparations. Materials and Method: In the present work, a simple and sensitive high performance thin layer chromatographic method is developed for determination of yohimbine (occurring as yohimbine hydrochloride) in pharmaceutical preparations and validated according to International Conference of Harmonization (ICH) guidelines. The method employed thin layer chromatography aluminum sheets precoated with silica gel as the stationary phase and the mobile phase consisted of chloroform:methanol:ammonia (97:3:0.2), which gave compact bands of yohimbine hydrochloride. Results: Linear regression data for the calibration curves of standard yohimbine hydrochloride showed a good linear relationship over a concentration range of 80–1000 ng/spot with respect to the area and correlation coefficient (R2) was 0.9965. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 5 and 40 ng/spot, respectively. The proposed method efficiently separated yohimbine hydrochloride from other components even in complex mixture containing powdered plants. The amount of yohimbine hydrochloride ranged from 2.3 to 5.2 mg/tablet or capsule in preparations containing the pure alkaloid, while it varied from zero (0) to 1.5–1.8 mg/capsule in dietary supplements containing powdered yohimbe bark. Conclusion: We concluded that this method employing high performance thin layer chromatography (HPTLC) in quantitative determination of yohimbine hydrochloride in pharmaceutical preparations is efficient, simple, accurate, and validated.

Validated HPLC and HPTLC Methods for Simultaneous Determination of Colchicine and Khellin in Pharmaceutical Formulations

The present work describes validated high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC) methods for the simultaneous determination of colchicine and khellin. The isocratic reversed-phase HPLC separation was performed on a 5 µm C18 column (Luna, Phenomenex, Torrance, CA). Good resolution between colchicine and khellin was achieved using a mixture of acetonitrile-10 mM NaH(2)PO(4) (pH 3.0, 35:65 v/v) as a mobile phase. Quantitation was achieved with ultraviolet detection at 245 nm based on peak area. The HPTLC separation was conducted on Merck HPTLC aluminum sheets of silica gel 60 F254 as stationary phase using methylene chloride-methanol (95:5 v/v) as a mobile phase. Quantification was also achieved using densitometric measurements at 245 nm. Both methods revealed reasonable validation parameters concerning selectivity, linearity, accuracy, precision and limits of detection and quantitation.