Ali A. El-Gamal

ANTHRAQUINONES FROM GALIUM SINAICUM

Abstract The new anthraquinones, 7-methylanthragallol 1,3-dimethyl ether, 7-methyl-anthragallol 2-methyl ether, 6-methylanthragallol 3-methyl ether, 8-hydroxyanthragallol 2,3-dimethyl ether, 7-formylanthragallol 1,3-dimethyl ether, copareolatin 5,7-dimethyl ether, copareolatin 6,7-dimethyl ether, 6-methoxylucidin ω-ethyl ether and 6-hydroxyxanthopurpurin, as well as a novel bianthraquinone, bisinaiquinone [10,2′-bi(9-hydroxy-3-methyl-1,4-anthraquinonyl)] were isolated from the roots of Galium sinaicum . Their structures were established by spectroscopic techniques including 2D-NMR. In addition, eight known anthraquinones were also isolated and fully characterized.

Noncyanogenic Cyanoglucoside Cyclooxygenase Inhibitors from Simmondsia chinensis.

Two new noncyanogenic cyanoglucoside dimers, simmonosides A and B (1 and 2), were identified from the aqueous extract of jojoba (Simmondsia chinensis) leaves. Compounds 1 and 2 are the first examples of noncyanogenic cyanoglucoside dimers containing a unique four-membered ring, representing novel dimerization patterns at α,β-unsaturated carbons of a nitrile group in 1 and γ,δ-unsaturated carbons in 2. Their structures were elucidated based on spectroscopic evidence and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 exhibit promising COX-2 inhibition activity, with IC50 values of 13.5 and 11.4 μM, respectively.

Studies on the red sea sponge Haliclona sp. for its chemical and cytotoxic properties

Background: A great number of novel compounds with rich chemical diversity and significant bioactivity have been reported from Red Sea sponges. Objective: To isolate, identify, and evaluate the cytotoxic activity of the chemical constituents of a sponge belonging to genus Haliclona collected from the Eastern coast of the Red Sea. Materials and Methods: The total ethanolic extract of the titled sponge was subjected to intensive chromatographic fractionation and purification guided by cytotoxic bioassay toward various cancer cell lines. The structures of the isolated compounds were elucidated using spectroscopic techniques including one-dimension and two-dimension nuclear magnetic resonance, mass spectrometry, ultraviolet, and infrared data, as well as comparison with the reported spectral data for the known compounds. X-ray single-crystal structure determination was performed to determine the absolute configuration of compound 4. The screening of antiproliferative activity of the compounds was carried on three tumor cell lines, namely the human cervical cancer (HeLa), human hepatocellular carcinoma (HepG2), and human medulloblastoma (Daoy) cells using MTT assay. Results: This investigation resulted in the isolation of a new indole alkaloid, 1-(1H-indol-3-yloxy) propan-2-ol (1), with the previously synthesized pyrrolidine alkaloid, (2R, 3S, 4R, 5R) pyrrolidine-(1-hydroxyethyl)-3,4-diol hydrochloride (4), isolated here from a natural source for the first time. In addition, six known compounds tetillapyrone (2), nortetillapyrone (3), 2-methyl maleimide-5-oxime (5), maleimide-5-oxime (6), 5-(hydroxymethyl) dihydrofuran-2 (3H)-one (7), and ergosta-5,24 (28)-dien-3-ol (8) were also identified. Most of the isolated compounds exhibited weak cytotoxic activity against HepG-2, Daoy, and HeLa cancer cell lines. Conclusion: This is the first report of the occurrence of the indole and pyrrolidine alkaloids, 1-(1H-indol-2-yloxy) propan-2-ol (1), and the - (1-hydroxyethyl)-3,4-diol hydrochloride (4), in the Red Sea Haliclona sp.

Cytotoxic Compounds from the Saudi Red Sea Sponge Xestospongia testudinaria

Bioassay-guided fractionation of the organic extract of the Red Sea sponge Xestospongia testudinaria led to the isolation of 13 compounds including two new sterol esters, xestosterol palmitate (2) and xestosterol ester of l6′-bromo-(7′E,11′E,l5′E)-hexadeca-7′,11′,l5′-triene-5′,13′-diynoic acid (4), together with eleven known compounds: xestosterol (1), xestosterol ester of 18′-bromooctadeca-7′E,9′E-diene-7′,15′-diynoic acid (3), and the brominated acetylenic fatty acid derivatives, (5E,11E,15E,19E)-20-bromoeicosa-5,11,15,19-tetraene-9,17-diynoic acid (5), 18,18-dibromo-(9E)-octadeca-9,17-diene-5,7-diynoic acid (6), 18-bromooctadeca-(9E,17E)-diene-7,15-diynoic acid (7), 18-bromooctadeca-(9E,13E,17E)-triene-7,15-diynoic acid (8), l6-bromo (7E,11E,l5E)hexadeca-7,11,l5-triene-5,13-diynoic acid (9), 2-methylmaleimide-5-oxime (10), maleimide-5-oxime (11), tetillapyrone (12), and nortetillapyrone (13). The chemical structures of the isolated compounds were accomplished using one- and two-dimensional NMR, infrared and high-resolution electron impact mass spectroscopy (1D, 2D NMR, IR and HREIMS), and by comparison with the data of the known compounds. The total alcoholic and n-hexane extracts showed remarkable cytotoxic activity against human cervical cancer (HeLa), human hepatocellular carcinoma (HepG-2), and human medulloblastoma (Daoy) cancer cell lines. Interestingly, the dibrominated C18-acetylenic fatty acid (6) exhibited the most potent growth inhibitory activity against these cancer cell lines followed by Compounds 7 and 9. Apparently, the dibromination of the terminal olefinic moiety has an enhanced effect on the cytotoxic activity.

Persicaline, A New Antioxidant Sulphur-Containing Imidazoline Alkaloid from Salvadora persica Roots

Salvadora persica L. is a popular chewing stick commonly known as “miswak”. During our ongoing research activities on the chemical constituents of Salvadora persica roots, which is a new sulphur-containing imidazoline alkaloid 1,3-Dibenzyl-4-(1,2,3,4-tetrahydroxy-butyl)-1,3-dihydro-imidazole-2-thione, persicaline, (1) along with five known compounds (2–6) are identified. Compounds (2, 3) were reported for the first time from the family Salvadoraeceae. The structure of the new compound was established by extensive spectroscopic data and HR-MS. The antioxidant activities of the fractions and isolates were evaluated using different in vitro methods, such as DPPH, superoxide anion and nitric oxide radicals scavenging assays. Compound (1) showed a promising antioxidant activity with IC50 0.1, 0.08, and 0.09 µM in the three assays, respectively, comparable to ascorbic acid.

The Phytochemical and Biological Investigation of Jatropha pelargoniifolia Root Native to the Kingdom of Saudi Arabia

Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-β-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (8–10), coumarin (15), pyrimidine (12), indole (17, 18), and tyramine-derived molecules (19–22). The anti-inflammatory, analgesic, and antipyretic activities were evaluated for fifteen of the adequately available isolated compounds (1–6, 8–11, 13, 14, 16, 21, and 22). Seven (4, 6, 10, 5, 13, 16, and 22) of the tested compounds showed a significant analgesic effect ranging from 40% to 80% at 10 mg/kg in two in vivo models. Compound 1 could also prove its analgesic property (67.21%) when it was evaluated on a third in vivo model at the same dose. The in vitro anti-inflammatory activity was also recorded where all compounds showed the ability to scavenge nitric oxide (NO) radical in a dose-dependent manner. However, eight compounds (1, 4, 5, 6, 10, 13, 16, and 22) out of the fifteen tested compounds exhibited considerable in vivo anti-inflammatory activity which reached 64.91% for compound 10 at a dose of 10 mg/kg. Moreover, the tested compounds exhibited an antipyretic effect in a yeast-induced hyperthermia in mice. The activity was found to be highly pronounced with compounds 1, 5, 6, 10, 13, and 16 which decreased the rectal temperature to about 37 °C after 2 h of the induced hyperthermia (~39 °C) at a dose of 10 mg/kg. This study could provide scientific evidence for the traditional use of J. pelargoniifolia as an anti-inflammatory, analgesic, and antipyretic.

Chemical composition and biological activity of the essential oil from the root of Jatropha pelargoniifolia Courb. native to Saudi Arabia

The chemical composition of the essential oil from Jatropha pelargoniifolia roots was determined via GC-FID. There were 80 compounds, representing 99.99% of the total oil constituents. Among these, 77.31% were sesquiterpenes, 14.62% were fatty acids, 7.21% were other components (i.e., phenolics, hydrocarbons, etc.), and 0.85% were monoterpenes. The major compounds in the oil were γ-eudesmol (35.31%), 5-guaien-11-ol (14.43%), epi-cedrol (8.19%), oleic acid (5.23%), bulnesol (4.45%), α-linoleic acid (4.20%), 3,4-dimethoxycinnamic acid (3.83%), palmitic acid (2.69%), isolongifolanone (2.68%), eicosane (1.41%), and cedrol (1.14%). Oxygenated sesquiterpenes were found to represent more than 50% percent of the total oil content. Moreover, the essential oil was evaluated for anti-inflammatory, antioxidant, antipyretic, and antinociceptive activities using in vivo and in vitro models. Additionally, the antioxidant potential of the oil was evaluated using various in vitro antioxidant tests, including DPPH•, ABTS•+ and FRAP. At a dose of 240 µl/kg, the oil showed anti-inflammatory (59.12%), antipyretic (37.00 ± 0.11), and antinociceptive (47.58%) activities and showed significant (p < 0.001) effect as compared to a standard drug (phenylbutazone and indomethacin). These findings demonstrated that the essential oil of Jatropha pelargoniifolia root could be used as a natural source for their anti-inflammatory, antinociceptive, antipyretic, and antioxidant effects.

Comparative evaluation of cytotoxic, antimicrobial and antioxidant activities of the crude extracts of three Plectranthus species grown in Saudi Arabia

Natural products from medicinal plants represent major resource of novel therapeutic substances for combating serious diseases including cancers and microbial infections. The genus Plectranthus (Family: Labiatae) represents a large and widespread group of species with a diversity of traditional uses in treatment of various ailments. Therefore, this research study aimed to evaluate the cytotoxic, antimicrobial and antioxidant activities of three Plectranthus species growing in Saudi Arabia namely P. cylindraceus Hocst. ex Benth., P. asirensis JRI Wood and P. barbatus Andrews. Moreover, this work focused on the isolation of the active constituents responsible for the activities from the most active Plectranthus species. The extracts were tested for their cytotoxic activity against three cancer cell lines (Hela, HepG2 and HT-29), using MTT-test, antimicrobial activity against Gram positive, Gram negative bacterial and fungal strains using broth micro-dilution assay for minimum inhibitory and bactericidal concentrations (MIC and MBC) and antioxidant activity using scavenging activity of DPPH radical and β-carotene-linoleic acid methods. The ethanolic extracts of the Plectranthus species showed remarkable cytotoxic activity against all cancer cell lines with IC50 values ranging between 10.1 ± 0.33 to 102.6 ± 8.66 μg/mL and a great and antimicrobial activity with MIC values between 62.5 and 250 µg/mL. In addition, the three Plectranthus species showed almost moderate antioxidant activity. The most interesting cytotoxic and antimicrobial results were observed with the extract of P. barbatus. Consequently, this extract was partitioned between water and n-hexane, chloroform and n-butanol and tested. The cytotoxic activity resided predominantly in the n-hexane and chloroform fractions. The analysis of the chloroform fraction led to the isolation of four diterpenoid compounds, two of labdane- and two of abietane-type, which were identified as coleonol B, forskolin, sugiol and 5,6-dehydrosugiol. Purification of the n-hexane fraction led to isolation of a major abietane-type diterpene, which was identified as ferruginol. Sugiol, 5,6-dehydrosugiol and ferruginol were isolated for the first time from P. barbatus in this study. The isolated diterpenoids showed variable cytotoxic effects with IC50 values between 15.1 ± 2.03 and 242 ± 13.3 µg/mL, a great antimicrobial activity with MIC values between 15.6 and 129 µg/mL and a total antioxidant activity ranging from 23.1 ± 2.9 to 69.2 ± 3.8%.

Chemical Composition of Buddleja polystachya Aerial Parts and its Bioactivity against Aedes aegypti

Abstract A new acylatediridoid glycoside, 6-O-α-L-(2″-acetyl-4″-O-trans-isoferuloyl) rhamnopyranosyl catalpol (9) together with 18 known compounds belonging to the iridoids, flavonoids, triterpene saponin glycosides and phenylethanoids (1–8, 10–18) were isolated from the aerial parts and the flowers of Buddleja polystachya. Their structures were elucidated on the basis of spectroscopic evidence and comparison with that reported in the literature. Promising adulticidal activity was shown for all extracts when tested for adulticidal and larvicidal activities against Ae. aegypti mosquitoes. Therefore, isolated compounds (1–10, 12–14 and 19) were bioassayed for their adulticidal activity. Compound 1 (phytol) was highly active with an LD50 value of 1.27 ± 0.08 μg/mosquito against adult female Ae. aegypti.

New Cytotoxic Seco-Type Triterpene and Labdane-Type Diterpenes from Nuxia oppositifolia

Chromatographic purification of the n-hexane and dichloromethane extracts of Nuxia oppositifolia aerial parts, growing in Saudi Arabia, resulted in the isolation and characterization of three new labdane-type diterpene acids, 2β-acetoxy-labda-7-en-15-oic acid (1), 2β-acetoxy-7-oxolabda-8-en-15-oic acid (2), 2β-acetoxy-6-oxolabda-7-en-15-oic acid (3), and one new seco-triterpene, 3,4-seco olean-12-en-3,30 dioic acid (4), together with 10 known lupane, oleanane and ursane-type triterpenes, as well as the common phytosterols, β-sitosterol and stigmasterol (5–16). Their structures have been assigned on the basis of different spectroscopic techniques including 1D and 2D NMR. Moreover, 13 of the isolated compounds were tested on the human cancer cell lines HeLa (cervical), A549 (lung) and MDA (breast), and most of the compounds showed potent cytotoxic activities in vitro.