A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs), and -phenethylamine (14), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) (13a-b and 18). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. The synthesized DHIQCDS (18) was subjected to various chemical and biological investigations to evaluate its stability and prove its ability to cross the blood brain barrier and “lock-in” the brain. The in vitro chemical and enzymatic oxidation studies showed reasonable stability and adequate rate of conversion of DHIQCDS (18) to its corresponding quaternary metabolites. In vivo distribution study in rats revealed preferential concentration of the active moiety in the brain. Moreover, compounds (9a-b, 12a-b and 17) were screened for their in vitro MAO inhibitory activity compared to clorgyline as a reference compound. The inhibition profile was found to be competitive for both MAO-A and MAO-B isozymes with more selectivity toward MAO-A. Molecular docking study of compounds (9a-b, 12a-b and 17) and the suggested metabolites was carried out on both MAO-A and MAO-B isozymes. Observation of the docked poses revealed many interactions with many residues previously reported to have an effect on the inhibition of MAO enzyme.

A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs), and -phenethylamine (14), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) (13a-b and 18). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. The synthesized DHIQCDS (18) was subjected to various chemical and biological investigations to evaluate its stability and prove its ability to cross the blood brain barrier and “lock-in” the brain. The in vitro chemical and enzymatic oxidation studies showed reasonable stability and adequate rate of conversion of DHIQCDS (18) to its corresponding quaternary metabolites. In vivo distribution study in rats revealed preferential concentration of the active moiety in the brain. Moreover, compounds (9a-b, 12a-b and 17) were screened for their in vitro MAO inhibitory activity compared to clorgyline as a reference compound. The inhibition profile was found to be competitive for both MAO-A and MAO-B isozymes with more selectivity toward MAO-A. Molecular docking study of compounds (9a-b, 12a-b and 17) and the suggested metabolites was carried out on both MAO-A and MAO-B isozymes. Observation of the docked poses revealed many interactions with many residues previously reported to have an effect on the inhibition of MAO enzyme.

A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs), and -phenethylamine (14), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) (13a-b and 18). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. The synthesized DHIQCDS (18) was subjected to various chemical and biological investigations to evaluate its stability and prove its ability to cross the blood brain barrier and “lock-in” the brain. The in vitro chemical and enzymatic oxidation studies showed reasonable stability and adequate rate of conversion of DHIQCDS (18) to its corresponding quaternary metabolites. In vivo distribution study in rats revealed preferential concentration of the active moiety in the brain. Moreover, compounds (9a-b, 12a-b and 17) were screened for their in vitro MAO inhibitory activity compared to clorgyline as a reference compound. The inhibition profile was found to be competitive for both MAO-A and MAO-B isozymes with more selectivity toward MAO-A. Molecular docking study of compounds (9a-b, 12a-b and 17) and the suggested metabolites was carried out on both MAO-A and MAO-B isozymes. Observation of the docked poses revealed many interactions with many residues previously reported to have an effect on the inhibition of MAO enzyme.

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 mM, respectively. In contrast, compounds 1, 3 and 4 were inactive, with IC50 values greater than 50 mM. 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.

Pyridoacridines are a class of strictly marine-derived alkaloids that constitute one of the largest chemical families of marine alkaloids. During the last few years, both natural pyridoacridines and their analogues have constituted excellent targets for synthetic works. They have been the subject of intense study due to their significant biological activities; cytotoxic, antibacterial, antifungal, antiviral, insecticidal, anti-HIV, and anti-parasitic activities. In the present review, 95 pyridoacridine alkaloids isolated from marine organisms are discussed in term of their occurrence, biosynthesis, biological activities, and structural assig

Two new tetracyclic triterpenoids: integracides F (1) and G (2) have been isolated from the endophytic fungus Fusarium sp. isolated from the roots of Mentha longifolia L. (Labiatae) growing in Saudi Arabia. Their structures were established by UV, IR, 1D (1H and 13C), 2D (1H-1H COSY, HMQC, HMBC, and NOESY) NMR, and HRESIMS spectral data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. Compound 1 and 2 displayed potent cytotoxic activity towards BT-549 and SKOV-3 with IC50 values of 1.97 and 0.16 mg/mL and 1.76 and 0.12 mg/mL, respectively compared to doxorubicin (IC50 1.61 and 0.095 mg/mL, respectively). Moreover, they exhibited significant anti-leishmanial activity towards Leishmania donovani with IC50 values of 3.74 and 2.53 mg/mL, respectively and IC90 values of 5.11 and 8.89 mg/mL, respectively.

Ethnopharmacological relevance: Costus speciosus (Koen ex. Retz.) Sm. (crepe ginger, family Costaceae) is an ornamental plant used in traditional medicine for the treatment of inflammation, rheumatism, bronchitis, fever, headache, asthma, flatulence, constipation, helminthiasis, leprosy, skin diseases, hiccough, anemia, as well as burning sensation on urination. Aim of the study: The present study is designed to isolate and identify the active compounds from C. speciosus rhizomes and measure their anti-inflammatory activities. Materials and methods: The n-hexane–CHCl3 soluble fraction of the MeOH extract of C. speciosus rhizomes has been subjected to a repeated column chromatography, including normal silica gel and RP-18 column to give eight compounds. The structures of these compounds were established by UV, IR, 1D (1H and 13C), and 2D (1H–1H COSY, NOESY, HSQC, and HMBC) NMR experiments and HRESIMS data. In addition, the anti-inflammatory activity of compounds 1–8 was evaluated by measuring the levels IL-6, IL- 1β, TNF-α, COX-2, lipoxgenase-5, and PGE2 using enzyme-linked immunosorbent assay. Results: The n-hexane–CHCl3 soluble fraction afforded a new eudesmane acid, specioic acid (8), along with seven known compounds, 22,23-dihydrospinasterone (1), dehydrodihydrocostus lactone (mokko lactone) (2), dehydrocostus lactone (3), stigmasterol (4), arbusculin A (5), santamarine (douglanin) (6), and reynosin (7). Compounds 1, 4, and 5–7 were isolated for the first time C. speciosus. Compounds 1–4 displayed potent anti-inflammatory activity, while 7 and 8 showed moderate activity. Compounds 1–8 exhibited a concentration-related decrease in the levels of IL-1β, IL-6, TNF-α, PGE2, lipoxgenase-5, and COX-2. Compounds 5 and 6 did not significantly decrease levels of different cytokines, PGE2, lipoxgenase- 5, and COX-2 from PHA treatment at 1 mM. However, all tested compounds significantly decreased cytokines, PGE2, lipoxgenase-5, and COX-2 levels at concentration 100 mM. It is noteworthy that compounds 1–4 had the highest activity, where it lowered levels of cytokines, PGE2, lipoxgenase-5, and COX-2 to the extent that was no statistical difference from the control group. Thus, they decreased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) with decreased level of the target enzymes (COX-2 and lipoxgenase-5) and subsequent reduction of its inflammatory product (PGE2). Conclusion: Good anti-inflammatory activities exhibited of the isolated compounds from C. speciosus corroborate the usefulness of this plant in the traditional treatment of inflammation and related symptoms.

Ethnopharmacological relevance: Litchi chinensis Sonn. (Sapindaceae) has been widely used in many cultures for the treatment of cough, flatulence, stomach ulcers, diabetes, obesity, testicular swelling, hernia-like conditions, and epigastric and neuralgic pains. The ethnopharmacologial history of L. chinensis indicated that it possesses hypoglycemic, anticancer, antibacterial, anti-hyperlipidemic, anti-platelet, anti-tussive, analgesic, antipyretic, hemostatic, diuretic, and antiviral activities. Aim of the review: The aim of this review is to provide up-to-date information on the botanical characterization, distribution, traditional uses, and chemical constituents, as well as the pharmacological activities and toxicity of L. chinensis. Moreover, the focus of this review is the possible exploitation of this plant to treat different diseases and to suggest future investigations. Materials and methods: To provide an overview of the ethnopharmacology, chemical constituents, and pharmacological activities of litchi, and to reveal their therapeutic potentials and being an evidence base for further research works, information on litchi was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search (PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library, and pubs.acs.org/journal/jacsat). All abstracts and full-text articles were examined. The most relevant articles were selected for screening and inclusion in this review. Results: A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethno-medical uses of L. chinensis have been recorded in China, India, Vietnam, Indonesia, and Philippines. Phytochemical investigation revealed that the major chemical constituents of litchi are flavonoids, sterols, triterpenens, phenolics, and other bioactive compounds. Crude extracts and pure compounds isolated from L. chinensis exhibited significant antioxidant, anti-cancer, anti-inflammatory,anti-microbial, anti-viral, anti-diabetic, anti-obesity, hepato-protective, and immunomodulatory activities. From the toxicological perspective, litchi fruit juice and extracts have been proven to be safe at a dose 1 g/kg. Conclusions: Phytochemical investigations indicated that phenolics were the major bioactive components of L. chinensis with potential pharmacological activities. The ethnopharmacological relevance of L. chinensis is fully justified by the most recent findings indicating it is a useful medicinal and nutritional agent for treating a wide range of human disorders and aliments. Further investigations are needed to fully understand the mode of action of the active constituents and to fully exploit its preventive and therapeutic potentials. & 2015 Elsevier Ireland Ltd. All rights reserved

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (~ 25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ~75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3–9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ~168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (~ 25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ~75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3–9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ~168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.