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The total ethanolic extract, different fractions and crude polysaccharides of leaves of Abutilon hirtum (Lam.) Sweet, were evaluated for their antimicrobial and antiparasitic activities. The antimicrobial activity was determined using the disc diffusion method against Staphylococcus aureus (Gram-positive, Facultative anaerobic bacteria), Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa (Gram-negative, Facultative anaerobic bacteria), Candida albicans, C. krusei (Diploid fungi) and C. glabrata (haploid fungus). The antimalarial activity was examined on chloroquine-sensitive (D6, Sierra Leone) strain of Plasmodium falciparum protozoan and the antileishmanial activity was tested against Leishmania donovani. The results of the present study showed that the total extract exhibited the lowest MIC (11.8 μg/ml) against P. aeruginosa. While, the chloroform fraction showed low MIC (59.03, 181.72 and 364.03 μg/ml) against S. aureus, K. pneumoniae and P. aeruginosa, respectively. The petroleum ether fraction exhibited the lowest MIC value (3.00 μg/ml) against C. albicans, while the total extract showed the lowest MIC (33.11 μg/ml) against C. glabrata. A. hirtum leaves extract and fractions showed a weak antimalarial activity. On the other hand, the chloroform fraction of A. hirtum leaves exhibited a potent antileishmanial activity with the highest percentage of inhibition (78%) against Leishmania donovani AMASTTHP_Pinh.

Lotus corniculatus L. (Fabaceae) is widely grown in Egypt. It has a great history of folkloric medicinal uses. All fractions of aerial parts of L. corniculatus L. showed significant antioxidant and...

The chemical study of Cannabis sativa roots led to the isolation and identification of 10 compounds. Their chemical structures were unambiguously established on the basis of 1D and 2D NMR spectroscopy and mass spectrometry as friedelan-3-one (1), epifriedelanol (2), β-sitosterol (3), ergost-5-en-3-ol (4), methyl hexadecanoate (5), pentadecanoic acid (6), 10E-hexadecenoic acid (7), 4-hydroxy-3-methoxybenzaldehyde (8), β-sitosterol-β-D-glucoside (9) and p-coumaroyltyramine (10). Compounds 5–9 were reported for the first time from C. sativa roots. All the isolated compounds were tested for their antimicrobial activity. Compound 4 showed modest activity against Cryptococcus neoformans with an IC50 value of 13.7 μg/mL, while compound 10 displayed potent activity against Escherichia coli with an IC50 value of 0.8 μg/mL. A high-performance liquid chromatography method was developed and validated for the detection and quantification of p-coumaroyltyramine (10) in the extracts of different varieties of C. sativa roots.

Bignoniaceae Juss. (Bignonia family) includes many genera of high economic and medicinal values. It comprises 104 genera and 860 species. Markhamia genus is traditionally used in the treatment of several diseases. Literature survey showed few chemical works on the Markhamia platycalyx and nothing could be found about the antimicrobial study. This provoked us to carry out an extensive study of this plant including GC/MS for saponifiable matter and volatile oil. The main recognized fatty acids were linolenic (44.66%), followed by palmitic (30.63%) of the saponifiable matter composition. While, E-phytol was the major identified compound of the volatile oil composition (12.95%). Moreover, this study included the antimicrobial activity of the volatile oil. It exhibited a potent antibacterial effect against E. coli with MIC 7.48 μg/ml compared to the standard antibiotics MICs, amikacin (28.96 μg/ml) and gentamycin (26.44 μg/ml).

Two series of novel 1,2,4-triazol-3-yl-thioacetamide 3a-b and 4a-b and 5-pyrazin-2-yl-3H-[1,3,4]oxadiazole-2-thiones 9a-h were designed and synthesized. The compounds prepared have been identified using 1H NMR, 13C NMR and elemental analyses. The synthesized compounds 3a, 3b, 4a, 4b, 9a, 9b, 9d-e and 9f have been evaluated with α-difluoromethylornithine (DFMO) as a control drug for their in vitro antitrypanosomal activity against Trypanosoma brucei. Results showed that 3b was the most active compound in general and also more potent than control DFMO. 3b was 8 folds more potent than the reference with IC50 of 0.79 μM and IC90 of 1.35 μM, respectively compared to DFMO (IC50 = 6.10 μM and IC90 of 8.66 μM). The tested compounds showed moderate cytotoxicity with selectivity indices ranging from 12 (9d) to 102 (3b) against L6 cells. Docking study was performed into ten of T. brucei enzymes which have been identified as potential/valid targets for most of the antitrypanosomal agents. The results of the docking study revealed high binding scores toward many of the selected enzymes. A good correlation was observed only between log (IC50) of antitrypanosomal activity of the new compounds and their calculated Ki values against TryR enzyme (R2 = 0.726). Compound 3b, the most active as antitrypanosomal agents exhibited similar binding orientation and interaction to those of WP6 against TryR enzyme. However, in a next round of work, a complementary studies will be carried out to clarify the mechanism of action of these compounds.

Four new ceramides (1–4) were isolated from the sponge Monanchora clathrata, along with four epidioxysterols (5–8), two sterols (9, 10), uracil (11), and three triglycerides (12–14). All compounds were isolated for the first time from the genus Monanchora, also this is the first time for isolation and identification of compounds 5–8, and the ceramide moieties from the family Crambeidae. Acetylation of compounds (5–8) yielded two new chemically modified compounds (15, 16), in addition to the known 17, 18. Their chemical structures were elucidated using a combination of spectroscopic methods, including extensive 1D and 2D NMR, IR, HRESIMS, and GC/MS. The configuration of compounds 1–4 were assigned as 2S,3S,4R,2′R based on the modified Mosher’s reaction, optical rotation measurements and spectroscopic data comparison. The compounds were evaluated for their, cytotoxic, antiprotozoal, antimicrobial, and antimalarial potentials. Compound 1 showed remarkable cytotoxicity against MES-SA, MCF-7, and HK-2 cell lines with IC50 values of 3.29, 17.95 and 4.45 μM, respectively.

Cannabinoids are a group of terpenophenolic compounds in the medicinal plant Cannabis sativa (Cannabaceae family). Cannabigerolic acid, Δ9-tetrahydrocannabinolic acid A, cannabidiolic acid, Δ9-tetrahydrocannabinol, cannabigerol, cannabidiol, cannabichromene, and tetrahydrocannabivarin are major metabolites in the classification of different strains of C. sativa. Degradation or artifact cannabinoids cannabinol, cannabicyclol, and Δ8-tetrahydrocannabinol are formed under the influence of heat and light during processing and storage of the plant sample. An ultrahigh-performance liquid chromatographic method coupled with photodiode array and single quadruple mass spectrometry detectors was developed and validated for quantitative determination of 11 cannabinoids in different C. sativa samples. Compounds 1 – 11 were baseline separated with an acetonitrile (with 0.05% formic acid) and water (with 0.05% formic acid) gradient at a flow rate of 0.25 mL/min on a Waters Cortec UPLC C18 column (100 mm × 2.1 mm I. D., 1.6 µm). The limits of detection and limits of quantitation of the 11 cannabinoids were below 0.2 and 0.5 µg/mL, respectively. The relative standard deviation for the precision test was below 2.4%. A mixture of acetonitrile and methanol (80 : 20, v/v) was proven to be the best solvent system for the sample preparation. The recovery of all analytes was in the range of 97 – 105%. A total of 32 Cannabis samples including hashish, leaves, and flower buds were analyzed.

Two new iridoid glycosides, named 6 β - O -methyl-unedoside ( 1 ) and 6 β - O -methyl-5-deoxythunbergioside ( 2 ) along with two known phenyl propanoid glucoside compounds dolichandroside A ( 3 ) and verbascoside ( 4 ) were isolated from the aerial parts of Odontonema cuspidatum (Nees) Kuntze (Acanthaceae). Structure elucidation of the new compounds was established by interpretation of their 1D and 2D-NMR spectral data by comparing with literatures, HRESIMS and optical activity measurement. The isolated compounds were tested for their in vitro antimicrobial and antimalarial activities. Compound 4 showed a moderate antimicrobial activity against E. coli with IC 50 value of 17.5 μM in comparing with Vancomycin and Cefotaxime.

Achillea fragrantissima (Forssk) Sch. Bip. (Asteraceae) is one of the most important medicinal plant species in Egypt. Phytochemical investigation of the methanolic extract of A. fragrantissima led to the isolation of two phenolic compounds Piceol (1) and Veratric acid (2), which are reported for the first time from this plant. In addition, four known flavonoid compounds; Eupatilin 7-methyl ether (3), Chrysosplenol D (4), Cirsiliol (5), and Cirsimaritin (6) were isolated. Structure elucidation was achieved using spectroscopic techniques, including one-dimensional and two-dimensional nuclear magnetic resonance. Potential cytotoxic activities of the isolated compounds were measured by the sulphorhodamine B assay. Compounds 1, 2, 3, 4, 5, and 6 displayed cytotoxic activity against (MCF7) with IC50 values of 18.2, 15.7, 9.5, 8.33, 3.23, and 3.83 µg/ml, respectively, and against (HepG2) with IC50 values of 19.4, 41.2, 28.3, 20.8, 23.8, and 23.8 µg/ml, respectively. Also there was moderate cytotoxic activity against (A549) with IC50 values of 17.8, 13.6, 3.98, and 10.3 µg/ml for the compounds 1, 2, 4 and 5, respectively, and against (HeLa) with IC50 values of 10.1, 10.4, 4.88, and 3.98 µg/ml for the compounds 3, 4, 5, and 6, respectively. In addition, compounds 4 and 5 showed cytotoxic activity against (PC3) with IC50 values of 3.83 and 3.98 µg/ml, respectively. An in silico study was performed, where cirsiliol (5) and piceol (1) were docked into the active sites of the crystal structures of PI3K and Akt, two protein kinases which are involved in prostate and breast cancer proliferation and survival.

Two new α- Pyrone derivatives (1,2) have been isolated from the endophytic fungus Embellisia sp. The isolated compounds were chemically identified as 5-(3-S-hydroxybutyl)-4-methoxy-6-methyl-2H-pyran-2-one (1) and 4-(4-methoxy-6-methyl-2-oxo-2H-pyran-5-yl)butanoic acid (2). The chemical structures of 1 and 2 were determined based on one and two dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configuration of compound 1 was determined using modified mosher ester reaction. In vitro antileishmanial, antifungal, antibacterial and antimalarial activities of 1 and 2 were examined but they didn’t show promising activities.

Twenty compounds were determined in the tar of cigarette smoke. The tar was obtained using tobacco filters and then analyzed by liquid chromatography-mass spectrometry (LC-MS). Tobacco tar expressed marked decrease in the susceptibility of Staphylococcus aureus to penicillin, tetracycline and amoxicillin/clavulanic antibiotics and showed marked decrease in susceptibility of Candida albicans to the tested antifungals except for clotrimazole and ketoconazole. Tobacco tar decreased the permeability of the tested organisms to ethidium bromide in the presence of antimicrobials, after 2 h for both S. aureus (17.8-20%) and C. albicans (13.3-16.3%) and decreased the adherence of the tested microorganisms at concentrations above Minimal Inhibitory Concentration (MIC). Tobacco tar showed a marked increase in the hydrophobicity of the tested microorganisms by 2.5 to 7 fold. Tobacco tar increased or upregulated ALS1 and HWP1 genes that play an important role in adhesion, hyphae formation and biofilm formation of C. albicans and increased the expression of ica A gene that regulate biofilm formation of S. aureus. Key words: Tobacco tar, Staphylococcus aureus, Candida albicans, antimicrobial susceptibility, ethidium bromide, biofilm formation.

Introduction: Decarboxylation is an important step for efficient production of the major active components in cannabis, for example, Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabigerol (CBG). These cannabinoids do not occur in significant concentrations in cannabis but can be formed by decarboxylation of their corresponding acids, the predominant cannabinoids in the plant. Study of the kinetics of decarboxylation is of importance for phytocannabinoid isolation and dosage formulation for medical use. Efficient analytical methods are essential for simultaneous detection of both neutral and acidic cannabinoids. Methods: C. sativa extracts were used for the studies. Decarboxylation conditions were examined at 80°C, 95°C, 110°C, 130°C, and 145°C for different times up to 60 min in a vacuum oven. An ultra-high performance supercritical fluid chromatography/photodiode array-mass spectrometry (UHPSFC/PDA-MS) method was used for the analysis of acidic and neutral cannabinoids before and after decarboxylation. Results: Decarboxylation at different temperatures displayed an exponential relationship between concentration and time indicating a first-order or pseudo-first-order reaction. The rate constants for Δ9-tetrahydrocannabinolic acid-A (THCA-A) were twice those of the cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA). Decarboxylation of THCA-A was forthright with no side reactions or by-products. Decarboxylation of CBDA and CBGA was not as straightforward due to the unexplained loss of reactants or products. Conclusion: The reported UHPSFC/PDA-MS method provided consistent and sensitive analysis of phytocannabinoids and their decarboxylation products and degradants. The rate of change of acidic cannabinoid concentrations over time allowed for determination of rate constants. Variations of rate constants with temperature yielded values for reaction energy.

Introduction: Cannabis sativa has been used for centuries in treating pain. However, the analgesic role of many of its constituents including terpenes is unknown. This research examined the contributions of terpenes (volatile oil) and cannabinoids in cannabis-mediated analgesia in rats. Methods: Animals received intraperitoneal administration of either vehicle, 10.0 or 18.0 mg/kg morphine, or various doses of the extract without terpenes, isolated terpenes, Δ(9)-tetrahydrocannabinol (THC), or the full extract. Thirty minutes later animals were tested on hotplate and tail-flick tests of thermal nociception. One week later, rats received a second administration of test articles and were tested 30 min later in the abdominal writhing test of inflammatory nociception. Results: In the thermal assays, hotplate and tail-flick latencies for morphine-treated rats were dose dependent and significantly higher than vehicle-treated animals. All the cannabinoid compounds except for the isolated terpenes produced dose-dependent increases in hotplate and tail-flick latencies. In the inflammatory nociceptive assay, animals treated with vehicle and isolated terpenes demonstrated increased abdominal writhing, whereas all the cannabinoid compounds significantly decreased abdominal writhing responses. Conclusions: Overall, THC alone produced robust analgesia equivalent to the full cannabis extract, whereas terpenes alone did not produce analgesia. These data suggest the analgesic activity of cannabis is largely mediated by THC, whereas terpenes alone do not cause alterations in cannabis-mediated analgesia.

A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI50 ranging from 19 to 100 μM and selectivity ratios ranging between 0.75 and 1.71 at the GI50 level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of −9.80 to −11.25 kcal/mol compared to −12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.

WOS: 000534529000001, The volatile oils of fresh and air-dried buds of 3 different varieties of Cannabis, namely, high cannabidiol (CBD) chemotype, inter- mediate CBD/tetrahydrocannabinol chemotype, and high THC chemotype were prepared by hydrodistillation. Gas chro- matography analysis of the volatile oils resulted in the identification of 71 compounds, of which 33 were monoterpenes and 38 were sesquiterpenes. the volatile oil obtained from the THC chemotype showed an increase in the ratio of the sesquiterpenes to monoterpenes content. the content of terpinolene was dramatically decreased upon drying of THC chemotype. Moderate increase in beta-caryophyllene and caryophyllene oxide was observed. However, there was no detectable change in the percentage of monoterpenes and sesquiterpenes content in both the intermediate type and CBD chemotype upon drying. the insecticidal activity of the volatile oils was evaluated. the oil obtained from the fresh and dried high CBD cannabis showed good biting deterrent activity at 10 ug/cm(2) compared with N,N-diethyl-meta-toluamide at 4.78 mu g/cm(2), and good larvicidal activity., National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [N01DA-15-7793], The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported in part by the National Institute on Drug Abuse, contract #N01DA-15-7793.

Bioassay-guided fractionation of the marine sponge Lendenfeldia dendyi and the soft coral Sinularia dura resulted in the isolation of five polybrominated diphenyl ethers (1–5). The structures of the isolated compounds were determined using spectroscopic methods (1D and 2D NMR) and HRMS analyses. The absolute structures of compounds 1 and 2 were confirmed by X-ray analysis. Antimicrobial testing of the isolated compounds along with the acetylated derivative of compound 2 (2a) indicated that they displayed a significant and selective activity against methicillin-resistant Staphylococcus aureus (MRSa) with IC50 values of

Alcea rosea L. is widely cultivated in gardens of Egypt as an ornamental plant and it has a great history of folkloric medicinal uses. In the present work, phytochemical investigation of the alcoholic extract of the flowers of A. rosea L. led to the isolation of six flavonoids (1–6). Dihydrokaempferol-4′-O-β-d-glucopyranoside (1), dihydrokaempferol (2), kaempferol-3-O-[6″-(E-coumaroyl)]-β-d-glucopyranoside (3), kaempferol-3-O-β-d-glucopyranoside (4), Apigenin (5) and kaempferol-3-O-α-l-rhamnopyranosyl-(1′″→6″)-β-d-glucopyranoside (6). Four of the isolated compounds were evaluated for their antioxidant, immunostimulant and cytotoxic activities against HepG-2 cell line. Compound (3) showed potent cytotoxic activity against HepG-2 cell line with high selectivity towards hepatocellular carcinoma in vitro (with IC50 = 3.8 μg/mL). Compounds 1 and 2 exhibited significant antioxidant activity and compound 4 showed a significant immune stimulant activity. Compound 1 is isolated for the first time from genus Alcea and this is the first report for its biological investigation.

An HPLC single-laboratory validation was performed for the detection and quantification of the 11 major cannabinoids in most cannabis varieties, namely, cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabidiol (CBD), tetrahydrocannabivarin (THCV), cannabinol (CBN), Δ9-trans-tetrahydrocannabinol (Δ9-THC), Δ8- trans-tetrahydrocannabinol (Δ8-THC), cannabicyclol (CBL), cannabichromene (CBC), and Δ9-tetrahydrocannabinolic acid-A (THCAA). The analysis was carried out on the biomass and extracts of these varieties. Methanol–chloroform (9:1, v/v) was used for extraction, 4-androstene-3,17-dione was used as the internal standard, and separation was achieved in 22.2 min on a C18 column using a two- step gradient elution. The method was validated for the 11 cannabinoids. The concentration-response relationship of the method indicated a linear relationship between the concentration and peak area with r2 values of >0.99 for all 11 cannabinoids. Method accuracy was determined through a spike study, and recovery ranged from 89.7 to 105.5% with an RSD of 0.19 to 6.32% for CBDA, CBD, THCV, CBN, Δ9-THC, CBL, CBC, and THCAA; recovery was 84.7, 84.2, and 67.7% for the minor constituents, CBGA, CBG, and Δ8-THC, respectively, with an RSD of 2.58 to 4.96%. The validated method is simple, sensitive, and reproducible and is therefore suitable for the detection and quantification of these cannabinoids in different types of cannabis plant materials.

The cannabis plant is one of the oldest plants known in medicine, with many reported medicinal uses for > 5,000 years. However, the chemistry of the plant was not fully investigated till the chemical structure of the active component was determined in 1964. Since then, over 10,000 scientific citations could be found on cannabis and the cannabinoids. The legal status of cannabis in the United States has been in a state of controversy. Although the drug in classified as a Schedule I Controlled Substance, therefore, illegal to possess without appropriate Drug Enforcement Administration (DEA) Registration, 23 states and the District of Columbia have passed laws allowing the medical use of cannabis. Furthermore, Colorado and Washington State have passed legislations allowing recreational use of the drug as well. Over the past few years there has been a tremendous public interest in cannabis and cannabis oil, with many growers sprouting in all states with legal medical use. The medical community and the end users have also shown much interest in knowing the composition of the materials on the market. Several laboratories have reported on methods to determine the chemical composition of the cannabis products, particularly the Δ9-THC and the CBD levels, along with a few other cannabinoids. This report is directed toward an ultra-high performance liquid chromatographic method (UHPLC) with UV detection for the quantitation of eleven different cannabinoids with base line separation namely cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, tetrahydrocannabivarin, cannabinol, Δ9-tetrahydrocannabinol, Δ8-tetrahydrocannabinol, cannabicyclol, cannabichromene, and Δ9-tetrahydrocannabinolic acid A. The method was validated and applied to the analysis and profiling of different varieties of cannabis produced at the UM Medicinal Plants Garden, as well as for the analysis of several confiscated cannabis preparations. The LOD, LOQ and linearity of the method were 0.2 – 0.4 µg/mL, 0.5 – 1.0 µg/mL and 1.0 – 200 µg/mL respectively, for all eleven cannabinoids.