Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Drug delivery using synthetic nanoparticles including porous silicon has been extensively used to overcome the limitations of chemotherapy. However, their synthesis has many challenges such as lack of scalability, high cost, and the use of toxic materials with concerning environmental impact. Nanoscale materials obtained from natural resources are an attractive option to address some of these disadvantages. In this paper, a new mesoporous biodegradable silicon nanoparticle (SiNP) drug carrier obtained from natural diatom silica mineral available from the mining industry is presented. Diatom silica structures are mechanically fragmented and converted into SiNPs by simple and scalable magnesiothermic reduction process. Results show that SiNPs have many desirable properties including high surface area, high drug loading capacity, strong luminescence, biodegradability, and no cytotoxicity. The in-vitro release results from SiNPs loaded with anticancer drugs (doxorubicin) demonstrate a pH-dependent and sustained drug release with enhanced cytotoxicity against cancer cells. The cells study using doxorubicin loaded SiNPs shows a significantly enhanced cytotoxicity against cancer cells compared with free drug, suggesting their considerable potential as theranostic nanocarriers for chemotherapy. Their low-cost manufacturing using abundant natural materials and outstanding chemotherapeutic performance has made them as a promising alternative to synthetic nanoparticles for drug delivery applications.

Abstract 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.

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.

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.