Mohamed Marzouk

Anticancer and Antioxidant Tannins from Pimenta dioica Leaves

Two galloylglucosides, 6-hydroxy-eugenol 4-O-(6′-O-galloyl)-β-D-4C1-glucopyranoside (4) and 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol-2-O-(2′,6′-di-O-galloyl)-β-D-4C1-glucopyranoside (7), and two C-glycosidic tannins, vascalaginone (10) and grandininol (14), together with fourteen known metabolites, gallic acid (1), methyl gallate (2), nilocitin (3), 1-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-(α/β)-d-glucopyranose (5), 4,6-(S)-hexahydroxydiphenoyl-(α/β)-d-glucopyranose (6), 3,4,6-valoneoyl-(α/β)-d-glucopyranose (8), pedunculagin (9), casuariin (11), castalagin (12), vascalagin (13), casuarinin (15), grandinin (16), methyl-flavogallonate (17) and ellagic acid (18), were identified from the leaves of Pimenta dioica (Merr.) L. (Myrtaceae) on the basis of their chemical and physicochemical analysis (UV, HRESI-MS, 1D and 2D NMR). It was found that 9 is the most cytotoxic compound against solid tumour cancer cells, the most potent scavenger against the artificial radical DPPH and physiological radicals including ROO•, OH•, and O2-•, and strongly inhibited the NO generation and induced the proliferation of T-lymphocytes and macrophages. On the other hand, 3 was the strongest NO inhibitor and 16 the highest stimulator for the proliferation of T-lymphocytes, while 10 was the most active inducer of macrophage proliferation .

Polyphenolic profile and biological activity of Salvia splendens leaves

Objectives  The aim of this study was to investigate a new flavone triglycoside, together with eleven phenolic metabolites from 80% aqueous methanol extract of S. splendens leaves (AME) and assessment of its hypoglycemic and antiinflammatory activities along with in vitro antioxidant effect.

Isoflavonoid Glycosides and Rotenoids from Pongamia pinnata Leaves

Chromatographic separation of a 70% aqueous methanol extract (AME) of Pongamia pinnata (Linn.) Pierre (Leguminosae) leaves has led to the isolation of two new isoflavonoid diglycosides, 4′-O-methyl-genistein 7-O-β-D-rutinoside (2) and 2′,5′-dimethoxy-genistein 7- O-β-D-apiofuranosyl-(1‴→ 6″)-O-β-D-glucopyranoside (6), and a new rotenoid, 12a-hydroxy-α-toxicarol (5), together with nine known metabolites, vecinin-2 (1), kaempferol 3-O-β-drutinoside (3), rutin (4), vitexin (7), isoquercitrin (8), kaempferol 3-O-β-d-glucopyranoside (9), 11,12a-dihydroxy-munduserone (10), kaempferol (11), and quercetin (12). Their structures were elucidated on the basis of chemical and spectroscopic analyses.

Biological effects of a new set 1,2,4-triazolo[1,5-a]quinazolines on heart rate and blood pressure

BackgroundSeveral quinazoline and triazole derivatives are reported to possess a wide-range of interesting pharmacological effects. Although various triazoloquinazoline subclasses having been synthesized and studied, the preparation of 1,2,4-triazolo[1,5-a]quinazolines as antihypertensive agent is still relatively unexplored. In continuation of our earlier research, we aimed at the synthesis and development of various potent antihypertensive 1,2,4-triazoloquinazoline derivatives.ResultsA new series of 1,2,4-triazolo[1,5-a]quinazoline derivatives have been synthesized. Their structures were mainly established by spectroscopic methods of analysis (IR, MS, 1H and 13C NMR). Their in vivo antihypertensive activity was evaluated by tail cuff method using Muromachi Blood Pressure Monitor (Model MK 2000) for rats and mice. Some of the tested compounds were found to exhibit valuable effects in terms of heart rate and blood pressure. According to the biological results, some of tested derivatives have abolished completely the tachycardia of the parent compounds and may be studied and modified as potential adrenoblockers and cardiac stimulant.ConclusionNew series of fifteen 1,2,4-triazolo[1,5-a]quinazolines were synthesized by convenient methodology from four key molecules, whereby their structures were established by advanced spectroscopic analyses. Some lead compounds have abolished completely the tachycardia of the parent compounds, that may be examined as potent adrenoblockers and some other compounds seem to be a cardiac stimulant or may be modified to enhance their hypotensive activity.

Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

A new series of quinazoline-4(3H)-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip) injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H)-ones (1–24) were examined in the maximal electroshock (MES) induced seizures and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100%) against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II). The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

Synthesis and anticancer activity of new quinazoline derivatives

In this study, a new series of quinazoline derivatives (3–26) was synthesized and characterized via physicochemical and spectral means. Treatment of 2-amino-5-methylbenzoic acid with butyl isothiocyanate resulted in the new 2-thioxoquinazolin-4-one (3). Alkylation and hydrazinolysis of the inherent thioxo group in (1–3) afforded the corresponding thioethers (4–23) and hydrazine derivatives (24 and 25), then 24 was further transformed into tricyclic derivative 26 via cyclocondensation reaction. Compounds 1 and 2, which were previously synthesized, were found to exhibit anticancer activity. The cytotoxicity of all compounds was evaluated in vitro against the HeLa and MDA-MB231 cancer cell lines, including 1 and 2 for comparison, using MTT assay. The treatment of the cells was performed with the synthesized compounds and gefitinib at 0, 1, 5, 10, 25, and 50 μM and incubated for 24 h in 50% DMSO. The IC50 values of the target compounds were reported in μM, using gefitinib as a standard. Our results indicated that all compounds exhibited significant in vitro cytotoxicity against both cell lines. While compounds 1–3 showed good activity, compounds 21–23 were found to be more potent than gefitinib. Thus, compounds 21–23 may be potential anticancer agents, with IC50 values ranging from 1.85 to 2.81 μM in relation to gefitinib (IC50 = 4.3 and 28.3 μM against HeLa and MDA-MB231 cells, respectively).

Antimicrobial Activity of New 2-Thioxo-benzo[g]quinazolin-4(3H)-one Derivatives

BACKGROUND The antimicrobial activity of a synthesized series of 28 2-thioxobenzo[ g]quinazolin-4(3H)-one derivatives was evaluated in vitro against five Gram-positive bacteria, including Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes. The antibacterial activity was extended to include five Gramnegative bacteria: Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Enterobacter cloacae. Furthermore, the antifungal activity was evaluated against 10 fungal strains, including Aspergillus fumigatus, Syncephalastrum racemosum, Geotricum candidum, Candida albicans, Aspergillus niger, Cryptococcus neoformans, Candida tropicalis, Penicillium expansum, Microsporum canis and Trichophyton mentagrophytes. METHODS The agar well diffusion method was adopted against Gram-positive and Gram-negative bacteria and fungi, using ampicillin, gentamicin and amphotericin B as reference drugs, respectively. RESULTS The findings of the antibacterial studies revealed that most of the tested compounds possess strong activity against both bacterial species. Compounds 8 and 23 were the most active on Grampositive bacteria, while several compounds demonstrated significant antibacterial activity on Gramnegative bacteria, especially Escherichia coli. Furthermore, several compounds showed strong antifungal activity against many of the investigated fungi. The obtained results were reinforced by determination of the minimum inhibitory concentration for the active compounds against Grampositive and Gram-negative bacteria, as well as fungi, compared to the reference drugs. CONCLUSION Many of the investigated compounds showed potent activity against all tested microbial species. The discovery has provided a foundation for the synthesized compounds to serve as a platform for further design and development of more potent antimicrobial agents.

Antimicrobial activity of newly synthesized methylsulfanyl-triazoloquinazoline derivatives.

The aim of this research was to study and evaluate the antimicrobial activity of a novel 2‐methylsulfanyl‐[1,2,4]triazolo[1,5‐a]quinazoline and its derivatives. Antibacterial activity of the target compounds was tested against a variety of species of Gram‐positive bacteria such as Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC6633, and Gram‐negative bacteria such as Pseudomonas aeruginosa ATCC27953 and Escherichia coli ATCC 25922. In addition some yeast and fungi, Candida albicans NRRL Y‐477 and Aspergillus niger, respectively, were screened.

In vitro evaluation of new 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives as antimicrobial agents

Previously, seventeen 2-phenoxy-benzo[g][1,2,4]triazolo[1,5-a]quinazoline derivatives were prepared and characterized by physicochemical and spectral means. This study was conducted to evaluate their activities in vitro against five Gram-negative and five Gram-positive of clinically pathogenic bacterial strains and ten fungal strains. The antimicrobial activity was assessed, and the minimum inhibitory concentration values of the tested compounds were determined in μg ml-1, using the diffusion agar technique. The bacterial strains used were Escherichia coli (ATCC 25922), Proteus mirabilis (ATCC 7002), Klebsiella oxytoca (ATCC 700324), Pseudomonas aeruginosa (ATCC 10145), Enterobacter cloacae (ATCC 13047D-5), Bacillus subtilis (NRRL B-543), Enterococcus faecalis (RCMB 0100154-2), Staphylococcus aureus (ATCC 29213), Staphylococcus epidermidis (ATCC 12228), and Streptococcus pyogenes (RCMB 0100174-2). Aspergillus fumigatus (RCMB 02568), Syncephalastrum racemosum (IMI 21178), Geotricum candidum (IMI 329542), Candida albicans (ATCC 10231), Aspergillus niger (IMI 130783), Cryptococcus neoformans (NRRL Y-1518), Candida tropicalis (RCMB 05239), Penicillium expansum (IMI 146655), Microsporum canis (RCMB 0834), and Trichophyton mentagrophytes (RCMB 0925) were used as the fungal strains. Ampicillin and gentamicin were used as reference antibacterial drugs and amphotericin B was used as the reference antifungal drug. The antimicrobial studies revealed that the tested compounds 6-8, 11, 12, and 14-16 showed the highest activities against the bacterial and fungal strains. The current study showed that some benzo[g]traizoloquinazolines displayed remarkable antimicrobial activity and could be used as template for further design of potent antimicrobial agent.

Antimicrobial Activity of Synthesized 2-Methylthiobenzo[g][1,2,4]- triazolo[1,5-a]quinazoline Derivatives

BACKGROUND The present study was carried out to evaluate the antimicrobial activity of a synthesized 2-methylthio-benzo[g][1,2,4]triazolo[1,5- a]quinazoline series. The compounds (1-21) were tested against a variety of Gram-positive bacterial species including Bacillus subtilis (RCMB 01001 69-3), Enterococcus faecalis (RCMB 0100154-2), Staphylococcus aureus (RCMB 0100183-9), Staphylococcus epidermidis (RCMB 0100183-9) and Streptococcus pyogenes (RCMB 0100172-5). In addition, Gram-negative bacteria were also tested including Pseudomonas aeruginosa (RCMB 0100243-5), Escherichia coli (RCMB 010052-6), Proteus mirabilis (RCMB 01002 54-2), Klebsiella oxytoca (RCMB 01002 83-4) and Enterobacter cloacae (RCMB 01002 64-5). Furthermore, their activities were screened against ten types of fungi i.e. Aspergillus fumigatus (RCMB 02568), Syncephalastrum racemosum (RCMB 05922), Geotricum candidum (RCMB 05097), Candida albicans (RCMB 05036), Aspergillus niger (RCMB 02724), Cryptococcus neoformans (RCMB 05642), Candida tropicalis (RCMBA 05239), Penicillium expansum (RCMB 01924), Microsporum canis (RCMB 0834) and Trichophyton mentagrophytes (RCMB 0925). METHODS Evaluation of antimicrobial activity was performed using agar well diffusion method in comparison with ampicillin and gentamycin as antibacterial reference drugs, and amphotericin B as antifungal reference drug. The minimum inhibitory concentration (MIC) was determined using the broth double dilution technique. RESULTS The MIC values of the tested compounds were reported in .g/mL in which ampicillin, gentamicin and amphotericin B were used as standard reference drugs. The obtained results revealed that compounds 3, 4, 7, 8, 9, 10, 11, 14, 17, 18, 19, 20 and 21 showed significant antimicrobial activity against six bacterial and six fungal strains. CONCLUSION The promising compounds could be employed as useful scaffolds for building of new derivatives with more potent antimicrobial effects.