The present study was designed to evaluate the safety of synthesized needle-like hydroxyapatite (HAp) nanoparticles ranging from 3 to 7 nm in diameter and from 27 to 46 nm in length when administered in female rats orally or subcutaneously at different concentrations.
Animals in different treatment groups were maintained on their respective diets as follows: group 1, untreated control; group 2, treated orally with HAp (300 mg/kg body weight) for 3 weeks; group 3, treated orally with a low dose of HAp (150 mg/kg body weight) for 3 weeks; and group 4, implanted subcutaneously with HAp (600 mg/kg body weight) once and left for 5 weeks. At the end of the experimentation period, blood samples were collected from all animals for biochemical analysis (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, uric acid, urea, and creatinine). After sacrifice, histopathological examination of the liver and kidney was carried out.
The biochemical results showed an increase in alanine aminotransferase and aspartate aminotransferase in the groups treated orally and those treated subcutaneously. There was an increase in alkaline phosphatase only in the group receiving the high oral dose; however, animals treated with the low dose or those treated subcutaneously were comparable with the control group. All the rats showed normal kidney function because of normal levels of creatinine, urea, and uric acid. The histopathological results indicated that the liver and kidney of all rats treated with HAp (oral or subcutaneously) had a normal structure. The previous results confirmed the safety of the synthesized nanoneedle HAp when administered orally or subcutaneously at the suggested dose.
A comparative study on the chemical composition as well as cytotoxic and antimicrobial activities of the brown algae Sargassum asperifolium, Sargassum dentifolium, and Sargassum linifolium (family: Sargassaceae) from the Red Sea, Hurghada, Egypt, is carried out.
The volatile constituents obtained by hydrodistillation as well as the isolated unsaponifiable matter and the fatty acids were analyzed using the gas chromatography/mass spectrometry technique. Antitumorigenic activities of the crude extracts of the three algae have been evaluated in vitro on different human cell lines. Furthermore, the antimicrobial activities of the volatile constituents, successive extractives, unsaponifiable matter, and fatty acids have been tested on 11 different microorganisms.
The analysis of the volatile fraction led to the identification of sexual pheromones, terpenes, phenolic compounds, free fatty acids, and esters. The most abundant sterols of unsaponifiable matter were fucosterol and cholesterol in all algae. Palmitic acid was found in all investigated algae as a major fatty acid. Biological screening proved that the tested algae have various cytotoxic and antimicrobial activities.
S. asperifolium, S. dentifolium, and S. linifolium are rich in cytotoxic and antimicrobial bioactive metabolites.
Heterocyclic systems with a quinoline nucleus display a wide spectrum of biological activities such as antimicrobial and antiviral activities. The aim of the present study was the synthesis of new fused pyranopyrazoles, 5a-e and 6a-e, and pyranoimidazoles, 10a-e and 11a-e, incorporated to 8-hydroxyquinoline through a sulfonyl bridge at position 5 and evaluation of their antimicrobial and antiviral activities.
The synthesis of the titled quinoline derivatives was achieved through cyclization of 8-hydroxyquinoline-5-sulfonyl chloride (1) with 2º-acetyl-2-cyanoacetohydrazide, 2-cyanoacetic acid hydrazide, and 3-amino-5-pyrazolone to afford 2, 3, and 4, respectively. Moreover, reaction of 1 with glycine gives 7, which on heterocyclization with ammonium thiocyanate yielded the 2-thioxoimidazolidin-2-one derivative 8. Cyclocondensation reaction of 3, 4, 8, and 9 with different arylidene malononitriles afforded fused systems, 5a-e, 6a-e, 10a-e, and 11a-e, respectively. The synthesized compounds were evaluated for their in-vitro antimicrobial activity using the disc diffusion method. In addition, they were evaluated for their in-vitro antiviral activity against avian paramyxovirus type 1 (APMV-1) and laryngotracheitis virus (LTV).
In-vitro antimicrobial activity of the newly synthesized compounds included an inhibitory effect toward the growth of Escherichia coli and Pseudomonas aeruginosa (Gram-negative bacteria). Furthermore, of the six selected compounds (2, 3, 4, 7, 8 and 9) tested for their antiviral activity, compounds 2, 3, and 4 at a concentration range of 3–4 µg/ml showed marked viral inhibitory activity for APMV-1 of 5000 tissue culture infected dose fifty (TCID50) and LTV of 500 TCID50 in Vero cell cultures on the basis of their cytopathic effect. Chicken embryo experiments show that compounds 2, 3, and 4 possess high antiviral activity in vitro, with inhibitory concentration fifty (IC50) ranging from 3 to 4 µg/egg against avian APMV-1 and LTV and toxic concentration fifty (CC50) ranging from 200 to 300 µg/egg.
The aim of part I is the synthesis of different series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadiazin-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (4–13) through the reaction of 4-[1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylidineamino]benzohydrazide (3) with different reagents to be evaluated biologically.
Derivatives of (1H-1,2,4-triazol-3-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one and (1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (4–6) were prepared by the reaction of 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) with benzyl, benzoyl isothiocyanate, or acetyl acetone to form 1H-1,2,4-triazole and 1H-pyrazole-5-nitroindolin-2-one derivatives. The reaction of 3 with ethyl bromoacetate, ethyl acetoacetate, or acetyl chloride afforded 1,3,4 oxadiazin-6-one, 3-methyl-5-oxo-4,5-dihydro-1H-pyrazole, or 1,3,4-oxadiazole-5-nitroindolin-2-one derivatives (7–9), respectively. Sugar hydrazone-5-nitroindolin-2-ones (10–13) were archived by the reaction of 3 with D-glucose, D-mannose, D-arabinose, and D-ribose using both conventional and green chemistry.
Conventional and microwave methods used for the synthesis of various triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindolin-2-one derivatives were applied for the synthesis of compounds 4–13. These methods were simple and gave good yields of the target compounds in short reaction times.
A new series of 2-(1,5,6-trimethyl-1H-benzo[d]imidazole-2-carbonyl)-2,3-dihydro-1H-pyrazole-4-carbonitrile (6a,b), (1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-5-yl)(phenyl) methanone (9–11), and (1,3,4-oxadiazol-2-yl)-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-8-carbonitrile (14–16) derivatives were synthesized and evaluated for their antioxidant and antimicrobial activities; in addition, their quantitative structure–activity relationships and molecular docking were investigated.
The target compounds 6a,b were synthesized by the following method: reaction of 5,6-dimethyl-1H-benzoimidazole-2-carbohydrazide (2) with 4-(dimethyl amino)benzaldehyde or anthracene-9-carbaldehyde yielded Schiff’s bases 3a,b, which were reacted with ethyl cyanoacetate to yield 1H-pyrazole-4-carbonitriles 4a,b; N-methylation of 4a,b afforded 5a,b, which reacted with 4-aminoantipyrine to give 6a,b. In addition, 5-benzoyl-1H-benzo[d]imidazole-2-carbohydrazide (8) or 8-cyano-6-isocyano-5-oxo-7-phenyl-1,5-dihydro-[1,2,4]triazolo[1,5-a]pyridine-2-carbohydrazide (13) reacted with different carboxylic acids such as crotonic acid, 3,4-diaminobenzoic acid, and 6-hydroxy-4-methoxybenzofuran-5-carboxylic acid to form compounds 9–11 and 14–16, respectively. The synthesized compounds were evaluated for their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, and the diffusion plate method for antimicrobial activity.
Among other tested compounds, compounds 15, 11, and 10 possessed the highest antioxidant activity, whereas compounds 4a, 5b, 6b, 10, and 11 displayed high activity against Staphylococcus aureus, Salmonella typhimurium, and Candida albicans. The quantitative structure–activity relationships of the studied compounds 4a, 4b, 5b, 6b, 10, 11, 14, 15, and 16 indicated a high correlation (r 2=0.82) between the predicted and actual activities as obtained from molecular descriptors and the inhibitory activity of this set of tested molecules measured as antioxidant activity. Moreover, the three-dimensional (3D) pharmacophore was generated, and docking of the most active antibacterial compound 4a against the dihydropteroate synthase enzyme gave comparable scores for hydrogen bond interaction (−13.5 kcal/mol) and binding mode to the reference antibiotic sulfamethoxazole (−13.00 kcal/mol).
Unconjugated hyperbilirubinemia (UCB) is one of the most common conditions in neonates. Conventional treatments are phototherapy and exchange transfusion. Phototherapy is safe and effective, but it has several disadvantages, which indicates the need to develop alternative pharmacological treatment strategies. These alternative treatment strategies should be less invasive and at least as effective and safe as phototherapy. The present study was designed to investigate the effects of Silybum marianum (silymarin) on the duration of phototherapy, which is known to have antioxidant, anti-inflammatory, hepatic-protective, and regenerative properties, including enhancing glucuronidation activities.
A randomized double-blind clinical trial was conducted on 170 full-term healthy neonates with UCB divided into two well-matched groups. Of the 170 neonates, 85 received 3.75 mg/kg of silymarin orally, twice daily, in addition to phototherapy, and 85 received placebo and phototherapy. Total serum bilirubin was measured every 24 h, and alanine aminotransferase (SGPT) and alanine transaminase (SGOT) levels were measured before and after therapy in both groups.
The mean duration of phototherapy was found to be significantly reduced from 5.3±0.82 days in the control group to 4.2±0.76 days in the silymarin-treated group (P=0.001). SGPT and SGOT levels were significantly normalized (P=0.001).
Silymarin at a dose of 3.75 mg/kg twice daily along with phototherapy was more effective than phototherapy alone in treating full-term healthy neonates with UCB.
The aim of this study was to evaluate comparative and structure–activity relationships of in-vitro cytotoxicity, antiviral and antioxidant activities of soyasapogenols A, B, D and F (SSA, SSB, SSD and SSF) together against the total soyasaponin extract (TSSE) itself.
The cytotoxicity of soyasapogenols and TSSE against human colon carcinoma cell line (HCT-116), liver carcinoma cell line (Hep-G2), human breast carcinoma cell line (MCF-7) and normal human melanocytes (HFB-4) cell lines was assessed using sulforhodamine B assay. Their antiviral activities were investigated against Rift Valley fever virus (RVFV), hepatitis C virus model (vesicular stomatitis virus, VSV), and hepatitis A virus (HAV). The antioxidant activity of soyasapogenols and TSSE was assessed using a stable DPPH free radical.
The results obtained showed that both TSSE and soyasapogenols have a potent cytotoxic effect on Hep-G2, HCT-116, MCF-7 and HBF-4 cell lines in a concentration-dependent manner. SSA and SSF showed the highest cytotoxic activities against tested cell lines. Analysis of the three-dimensional structure of the measured soyasapogenols indicated that if the β-hydroxyl group at C-21 or C-22 was aligned with the plane of the molecule, a marked increase in the cytotoxic activity of the soyasapogenol was produced. Their antiviral activities against RVFV, VSV and HAV showed significant inhibition activities compared with both TSSE and interferon. SSB showed the best activity against RVFV and HAV, whereas SSA was the best inhibitor against VSV. It was concluded that the hydroxylation at C-21 as well as the presence of a double bond in ring D might enhance anti-VSV activity, whereas they may not be essential for anti-RVFV and anti-HAV activities. On the other hand, the tested soyasapogenols and TSSE did not show good antioxidant activities.
There are a number of theories on which organisms provide the most interesting bioactive metabolites. In this study, we discuss the biochemical activities of the marine-derived endophyte Emericella nidulans, isolated from the Egyptian Red Sea algae.
The fungus E. nidulans was isolated as an endophyte from the Egyptian Red Sea brown alga Turbinaria elatensis. The fungus was identified by a morphological method and 18S rDNA sequence comparison. Chemical constituents were isolated using chromatographic techniques.
Cultivation of this fungus in Czapek’s peptone media led to the isolation of five known metabolites: sterigmatocystin (1), emericellin (2), cordycepin (3), ergosterol peroxide (4), and myristic acid (5) from the ethyl acetate extract of the culture broth. The structures were elucidated on the basis of NMR spectroscopic analysis and mass spectrometry. The ethyl acetate extract and the isolated compounds were tested for antimicrobial properties, activity against cancer cell lines, and inhibition of the hepatitis C virus protease.
Trialkyl phosphites 2a,b attack 6-(aryliminomethyl)furobenzopyran-5-ones 1a–e regiospecifically at the carbon–carbon double bond of the γ-pyrone ring to yield new 1,2-addition phosphonate products for which structures 3a–e have been respectively assigned.
The alkyl phosphites 2a,b attacked the monoanils 1a–e at the azomethine carbon of the C=N bond to yield corresponding phosphonate adducts 5a–e when reactions were carried out in the presence of a controlled amount of acetic acid. Phosphonates 5a–e could also be obtained by the reaction of dialkyl phosphites 4a,b with anils 1a–e. Structures of the new phosphonates 3a–e were elucidated by elemental analyses as well as spectroscopic methods. The 1H and 13C nuclear magnetic resonance and infrared measurements were helpful tools in confirming the structures of the new products.
The insecticidal activities of phosphonates 3a–e and their respective regioisomers 5a–e against adult Aphis gossypii (Glover), which infest cotton crops, were determined. The structure–activity relationship has been discussed.
The aim of this work was to study the purification and characterization of the crude extracellular laccase produced by the marine-derived fungus Trematosphaeria mangrovei.
The general properties of the crude laccase enzyme produced by T. mangrovei were investigated. These include the effect of temperature, pH, thermal and pH stabilities, and enzyme and substrate concentrations on the laccase activity. Partial purification of the T. mangrovei laccase enzyme was carried out by fractional precipitation with ammonium sulphate, ethanol and acetone. Further purification was carried out on a Sephadex G-100 column.
The results obtained showed that the crude enzyme reached its maximal activity at 35πC, pH 4.5, at an enzyme concentration of 5.429 mg protein/reaction mixture and at a substrate concentration of 40 mmol/l 2,2-azinobis-(3-ethylbenzthiazoline-6-sulphonic acid). The enzyme was stable for 60 min at 35πC and retained about 80–90% of its activity after treatment for 60 min from 40 to 50πC. The enzyme showed maximum stability (100%) at pH 4.5 and 91.6% at pH 4.0 after 60 min. Fractional precipitation of the fungal extracellular T. mangrovei laccase enzyme with different methods showed that the enzyme fraction precipitated at 60% acetone was the most favourable enzyme fraction; it showed 4.84 purification fold. Laccase obtained from the 50–60% acetone fraction was purified by Sephadex G-100. The final preparation thus obtained reached 31.47-fold that of the culture filtrate (1466.49 U/mg protein) and showed a single band on native polyacrylamide gel electrophoresis.
The aim of this study (part II) is to evaluate the antibacterial, anti-inflammatory, and antinociceptive activities of a series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadizine-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (1–13) and, in addition, to investigate their computational chemistry.
The synthesized compounds in (part I) 1–9 were evaluated for their antibacterial and antifungal activities using different strains of Gram-positive bacteria (Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa), yeast (Candida albicans), and four mold fungi (Fusarium solani, Aspergillus niger, Colletotrichum gloeosporioides, and Phomopsis obscurans). The anti-inflammatory and antinociceptive activities of compounds 1–13 were evaluated using a hot-plate test, acetic acid-induced writhing in mice, formalin-induced nociception, a tail immersion test, and carrageenan-induced hind paw edema. For computational chemistry, a semiempirical MNDO method (Modified Neglect of Differential Overlap is a semi-empirical method for the quantum calculation of molecular electronic structure in computational chemistry) associated with HyperChem professional 7.5 programs was adapted.
Compounds 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) and 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (9) showed the highest antibacterial and antifungal activities compared with clotrimazole and sulfamethoxazole as reference drugs. In contrast, compounds ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), 3-(4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl) phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (8), D-glucose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (10), and D-arabinose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (12) showed significantly high anti-inflammatory and antinociceptive activities when compared with indomethacin and morphine as reference drugs. From the computational chemistry compounds, ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), ethyl 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzoate (2), and 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) yielded the lowest values of total energy and heat of formation, and had higher stability than other molecules.