Mohamed E. Zain

New antifungal compounds from Aspergillus terreus isolated from desert soil.

Two new butyrolactone I derivatives: 3‐[3‐hydroxy‐4‐(3‐methyl‐but‐2‐enyl)‐phenyl]‐5‐(−4‐hydroxybenzyl)‐4‐methyl‐dihydrofuran‐2(3H)‐one (1) and (Z)‐3‐[3‐hydroxy‐4‐(3‐methyl‐but‐2‐enyl)‐phenyl]‐5‐(−4‐hydroxybenzylidene)‐4‐methyl‐dihydrofuran‐2(3H)‐one (2), in addition to the previously described (S)‐methyl‐4‐hydroxy‐2‐[4‐hydroxy‐3‐(3‐methyl‐but‐2‐enyl)‐benzyl]‐3‐(4‐hydroxy‐phenyl)‐5‐oxo‐2,5‐dihydro‐furan‐2‐carboxylic acid methyl ester (3), were identified from a strain of Aspergillus terreus Thom (Trichocomaceae) isolated from desert soil. The antifungal activities of both intra‐ and extracellular metabolites of A. terreus grown on yeast extract sucrose and malt extract media were determined. Only the secondary metabolites of A. terreus grown on yeast extract sucrose medium were active against Aspergillus fumigatus RCMB 002008. The antifungal activity of A. terreus was attributed to the presence of the compounds (1) and (2), whose minimum inhibitory concentrations (MIC) against A. fumigatus were found to be 32.00 and 16.00 µg/mL respectively. Structure elucidation was carried out using UV spectrometry, electrospray ionization mass spectrometry (ESIMS), high resolution electron impact (HREIMS) spectrometry, 1H‐ and 13 C‐NMR, proton–proton correlation spectroscopy (1H–1H Cosy), distortionless enhancement by polarization transfer (DEPT), heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlations (HMBC) spectroscopy. Copyright

Anti-leishmanial Activities of Extracts and Isolated Compounds from Drechslera rostrata and Eurotium tonpholium

The fungal extract of Drechslera rostrata and Eurotium tonpholium showed a significant anti‐leishmanial activity against Leishmania major; IC50 was 28.8 and 28.2 μg/mL, respectively. Seven compounds, five from D. rostrata (H1–H5) and two from E. tonpholium (H6 and H7), were isolated and identified using different spectroscopic analysis including 1HNMR, 13CNMR, Hetero‐nuclear multiple bond connectivity (HMBC), Hetero‐nuclear Multiple Quantum Correlation (HMQC), and EI‐MS. The isolated compounds are: di‐2‐ethylhexyl phthalate (1), (22E)‐5α,8α‐epidioxyergosta‐6,22‐diene‐3β‐ol (2),1,3,8‐trihydroxy‐6‐methyl‐nthraquinone (3), aloe‐emodine 8‐O‐glucopyranoside(4), 2R, 3R,4R,5R hexane 1, 2, 3, 4, 5, 6 hexole (Mannitol) (5), 1,8‐dihydroxy‐3‐methoxy‐6‐methyl‐anthraquinone (6) and 1, 4, 5‐trihydroxy‐7‐methoxy‐2‐methyl‐anthraquinone (7). However, compounds (1) and (6) showed activity against L. major with IC50 of 3.2 and 10.38 µg/mL, respectively. On the other hand, oral administration of the two extracts (100 mg/kg) and compounds 1 and 6 (50 mg/kg) showed very good activity when compared with the anti‐leishmanial drug Pentostam (125 mg/kg). Interestingly, the complete heeling activity of the extracts and compounds (1) and (6) was obtained after 13–17 days of treatment, while complete healing activity of Pentostam was obtained after 28 days. No alteration on liver and kidney functions was recorded on animals treated with the two extracts for 15 consecutive days. Copyright

Anti‐Ulcerative Colitis Activity of Compounds from Euphorbia granuleta Forssk

The aim of the present study was to evaluate the anti‐ulcerative colitis (UC) activity of the total alcohol extracts of Euphorbia granuleta Forssk. (Euphorpiaceae), isolate and identify the active compounds that could be responsible for the activity, in addition to determination of the possible mechanism of action. Six compounds were isolated and identified from this plant: three phenolic compounds (kampferol, kampferol‐3‐glucoside and kampferol‐3‐galactoside) in addition to three steroidal compounds (1‐ethoxypentacosane, heptacosan‐1‐ol and β‐sitosterol). Three compounds (heptacosan‐1‐ol, β‐sitosterol and kampferol‐3‐galactoside) were found to be responsible for the anti‐UC activity of E. granuleta extract. The anti‐UC activity of these compounds may be explained by reducing the pro‐inflammatory cytokine tumor necrosis factor‐alpha (TNF‐α), in addition to reduction of colonic malondialdehyde (MDA) contents. No side effects were reported on liver and kidney functions. The active compounds reduced both serum TNF‐α and mucosal MDA levels. Copyright

New Biological Activities of Casimiroa edulis Leaf Extract and Isolated Compounds

The phytochemical investigation of Casimiroa edulis Llave et Lex (Rotaceae) afforded four coumarins: umbelliferone (1), esculetin (2), imperatorin (3) and xanthotoxol (4). The identification of these compounds was achieved by using a combination of m.p., UV, EI‐mass, 1H NMR and 13C NMR spectroscopy. Essential oil extracts were analysed by GC/MS leading to the identification of 60 components. Sesquiterpene hydrocarbons accounted for the major make up of the oil. Microbiological screenings of the oil and successive plant fractions were performed, showing promising activity against a number of microorganisms with Minimum inhibitory concentrations (MIC) comparable to the standard antibiotics such as chloramphenicol and kanamycin. The plant ethanol extract (400 mg/kg) and the isolated coumarins (60 mg/kg) showed anticoagulant activity. Analyses to determine the activity of the extracts on liver and kidney function were performed, revealing no negative or detrimental effects. Copyright

Biological activity of fungal secondary metabolites

Abstract: Fungi are cosmopolitan organisms that inhabit almost all ecological niches of the earth and have the ability to utilise various substrates as a consequence of diversity of their biological and biochemical evolution. Fungi, during their development, follow different metabolic pathways that led to production of numerous intermediate and/or end-product compounds called as secondary metabolites. Fungi, filamentous forms, produce a diverse array of secondary metabolites that are small molecules, and not necessary for normal growth or development. Secondary metabolites have a tremendous impact on society; some are exploited for their antibiotic and pharmaceutical activities, others are involved in disease interactions with plants or animals. Most fungal secondary metabolites are synthesised from only a few key precursors in pathways that comprise a relatively small number of reactions and which branch off from primary metabolism at a limited number of points. However, the roles of secondary metabolites in the fungi that produce them are still more or less a mystery.

Synthesis and biological evaluation of certain 3-substituted benzylideneamino-2-(4-nitrophenyl)quinazolin-4(3H)-one derivatives.

Abstract Certain new 3H-quinazolin-4-one Schiff’s bases were synthesized and screened for their activities against ulcerative colitis “UC”. Their activity against phospholipase A2 and protease enzymes was also investigated. Some compounds possessed remarkable effect with different potentials against acetic acid-induced colitis model in rats. Compound 14 (50 mg/kg) was more effective than dexamesathone (0.01 mg/kg). It produced 79.78% protection of control colitis; however, compound 13 produced 75.80% protection and was considered as effective as dexamesathone with 75.30% protection. The observed results could be explained partially by their anti-inflammatory activities which appear as phospholipase A2 (hGIIA) and/or through protease inhibitor potentials. However, all the compounds under test showed preferential inhibition towards hG-IIA type of PLA2 rather than DrG-IB with varying degrees. Interestingly, compounds 14, 13, 12 and 11 displayed excellent inhibitory activity against phospholipase A2 accompanied by protease inhibitory profile.

Synthesis and hypoglycemic activity of some new theophylline derivatives.

Abstract Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%. Ten compounds showed varying degrees of hypoglycemic activity ranging from 20 to 37% reduction in serum glucose level compared to the standard drug. The aromatic amide functionality is the common feature of these theophylline hypoglycemic derivatives. However, anthranilamide and or aliphatic amides proved to be the least active compounds in the present series.

Protective role of Cynanchum acutum L. extracts on carbon tetrachloride-induced hepatotoxicity in rat

AIM: Evaluation of the hepatoprotective activity of Cynanchum acutum total alcohol and successive extracts. SETTINGS AND DESIGN: Total alcohol extract and successive extracts (ether, chloroform, ethyl acetate and butanol) of C. acutum were evaluated at different doses for hepatoprotective activity. MATERIALS AND METHODS: Carbon tetrachloride-induced hepatitis method was used. The activity of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and serum levels of total protein (TP), albumin (Alb), total bilirubin (TB), total cholesterol and triglyceride levels were determined to evaluate liver damage in rats. STATISTICAL ANALYSIS: One-way analysis of variance (ANOVA) followed by Bonferoni’s test to determine the intergroup variability by using SPSS version 14.0. RESULTS: Pre-treatment of rats with the investigated extract (50, 100, 200 mg/kg), successive extracts (10 mg/ kg) effectively protected rats against CCl4-induced hepatic damage, resulting in reduction in the elevated serum activities of liver marker enzymes (ALT, AST and ALP) in addition to elevating the lowered serum levels of TP and Alb and lowering the serum levels of TB, triglyceride and cholesterol when compared with the normal control rats, where the total extract at dose 200 mg/kg was the most effective extract. Total alcohol extract (200 mg/kg) administrated daily to rats for 15 consecutive days did not show any alterations on liver and kidney functions. CONCLUSIONS: The high flavonoidal content of the investigated extract could be responsible for the potent hepatoprotective activity where the mechanism was related to the ability of the extract to inhibit lipid peroxidation in the liver by inhibiting the free radical mediated damage.

Developments in using fatty acids in fungal chemotaxonomy

The cellular fatty acid composition of nine species of Fusarium; namely, Fusarium anthophilum, F. avenaceum, F. cerealis, F. graminearum, F. graminum, F. oxysporum f. sp. conglutinans, F. pseudograminearum, F. roseum and F. sacchari var. elongatum growing on malt extract medium were determined. The fatty acid profiles of the investigated fungi showed very little variation and could only differentiate between few species. However, by adding certain chemical compounds including aspartic acid, glutamic acid, methionine, selenium and urea to the growth medium, the variation of the fatty acid profile was greatly increased and differentiated between all the investigated fungi. For example, pentadecanoic acid was not produced by F. anthophilum on malt extract broth (MEB) but only produced on MEB supplemented with aspartic acid. On the other hand, linolenic fatty acid was neither produced by F. anthophilum nor F. roseum grown on MEB, but it was produced by F. anthophilum in presence of aspartic acid and by F. roseum in the presence of glutamic acid. The fatty acid profiles could be useful for characterization and identification of fungi if determined under different conditions.

Anticandidal Activity of Extracts and a Novel Compound, Amnomopin, Isolated From Petriella setifera

A novel triterpenoidal compound named ‘amnomopin’ (3β‐diglucoside‐5,12‐28‐oic acid), which is named IUPAC as 3‐O‐(2′ ➔ 1″diglucoside)1,2,3,4,4a,5,6,6a,6b,7,9,10,11,12,12a,12b,13,14b‐octadecahydro‐10‐hydroxy‐2,2,6a,6b,9,9,12a‐heptamethylpicene‐4a‐carboxylic acid, was isolated from the extract Petriella setifera. The total alcoholic extract of P. setifera showed a great activity against clinically isolated Candida species, including Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida inconspicua, Candida kefyr, Candida krusei, Candida norvegensis, Candida parapsilosis and Candida tropicalis. Also, the new compound amnomopin was active against all the investigated Candida species. The highest anticandidal activity of P. setifera extract was obtained against C. kefyr (22.6 ± 1.5 mm), C. albicans and C. norvegensis (21.3 ± 0.63 mm) and C. krusei (20.6 ± 1.5 mm). Moreover, the minimum inhibitory concentrations of both the total extract and the isolated compound were low. The minimum inhibitory concentration of the compound isolated from P. setifera was 0.49 μg/mL against C. kefyr, 0.98 μg/mL against C. albicans and C. norvegensis and 1.95 μg/mL against C. krusei. The oral dosing of the extract and the isolated compound did not show any significant effect on the activity of alanine aminotransferase, aspirate aminotransferase and the levels of blood urea and serum creatinine. Copyright