Synthesis of new phenylcarbamoylbenzoic acid derivatives and evaluation of their in?vitro antioxidant activity

In this study, new derivatives of phenylcarbamoylbenzoic acid were synthesized and evaluated for their in?vitro antioxidant activity. The target compounds were prepared by bonding pharmacophoric moieties possessing antioxidant activity, including hydrazones, acid hydrazides, imino, Schiff’s bases, and phthalimides with phenylcarbamoylbenzoic acid via simple and efficient synthetic strategies. The structures of the newly synthesized compounds were confirmed by physical and spectral data. The in?vitro antioxidant activity was carried out using ABTS antioxidant assay. All the tested compounds showed low antioxidant activity except compound 7, which showed moderate antioxidant activity compared with ascorbic acid.     

Antimutagenic, antioxidant and free radical scavenging activity of ethyl acetate extracts from white, yellow and red onions.

The beneficial effects of red, yellow and white onion extracts have been assessed by antioxidant activity and antimutagenic activity. And the effects compared to BHT and ascorbic acid. Total phenolic compounds and flavonoids in onion extracts were determined. Yellow onion extract had more organic acid and free sugar than those detected in the white and red onion extract. The scavenging activity of DPPH radical and H(2)O(2) were increased depending on the concentration. The antioxidant activities using beta-carotene-linoleate system and reducing power were increased but the effect was small to that of BHT and ascorbic acid. After digested, extracts showed antimutagenic activities, and it seems that they inhibit the mutagenicity for digesting. This study demonstrated that the antimutagenicities and antioxidant properties of ethyl acetate extract against mutagens were related to their phenols and flavonoids, which are heat stable and losses digestive juices are relatively low.     

A review on biological activities and chemical synthesis of hydrazide derivatives

There has been considerable interest in the development of novel compounds with anticonvulsant, antioxidant, hormone antagonist, analgesic, anti-inflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and anti-trypanosomal activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazide derivatives that possess varied biological activities.     

Synthesis of some hydroxamic acid derivatives of benzimidazole and their antibacterial and antifungal activities.

A number of 1H-benzimidazole-2-propanoic acid derivatives have been synthesized by Phillips method, and their antibacterial and antifungal activities have been tested. The chemical structures of the synthesized compounds were elucidated by spectroscopic (IR, NMR, mass) and elementary analysis. Investigation of antimicrobial activity of the compounds was done by agar dilution technique using bacteria (Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Mycobacterium smegmatis ATCC 607) and yeast-like fungi (Candida albicans, Candida tropicalis, Candida pseudotropicalis, Candida kruzei, Candida globrata). Among the compounds tested N-hydroxy-3-(1H-benzimidazol-2-yl)-propionamide (Compound 6) showed considerable activity against both Candida albicans and Candida tropicalis.     

Isolation and frontier molecular orbital investigation of bioactive quinone-methide triterpenoids from the bark of Salacia petenensis

The crude dichloromethane bark extract of Salacia petenensis (Hippocrateaceae) from Monteverde, Costa Rica, shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of tingenone and netzahualcoyonol as the biologically active materials. Also isolated from the extract were 3-methoxyfriedel-2-en-1-one (a new natural product) and 29-hydroxyfriedelan-3-one. The structures of these compounds were elucidated on the basis of NMR spectral analysis. Molecular orbital calculations have been carried out using the semi-empirical PM3 and Hartee-Fock 3-21G ab initio techniques on the quinone-methide nortriterpenoids tingenone and netzahualcoyonol, as well as on the nucleotide bases adenine, guanine, cytosine, and thymine. The molecular orbital calculations suggest that a possible mode of cytotoxic action of quinone-methide triterpenoids involves quasi-intercalative interaction of the compounds with DNA followed by nucleophilic addition of the DNA base to carbon-6 of the triterpenoid.     

New p-Substituted Salicylaldehyde Phenylhydrazone Derivatives: Synthesis,Characterization, and Antioxidant Activities

A series of new p-nitrophenylhydrazone derivatives 3a–f were synthesized, characterized, and investigated for their antioxidant activities. These compounds have been synthesized by refluxing (p-nitrophenyl)hydrazine with 4-sub-stituted salicylaldehydes. The structures of the compounds were established by IR, ¹H- and ¹³C-NMR, and MS data. The antioxidant activities (free radical-scavenging activity, reducing power, metal chelating activity, and total anti-oxidant activity) of the hydrazone compounds were evaluated. All of the compounds exhibited significant activities, while compound 3a, with the shortest chain, showed the highest antioxidant activity in all of the tests.     

Conformational analysis and molecular properties of N-(substituted phenyl-carbonylamino)-4-(1-hydroxymethylphenyl)-1,2,3,6-tetrahydropyridines

The three-dimensional structures of active derivatives of N-(substitutedphenylcarbonylamino)-4-(1-hydroxymethylphenyl)-1,2,3,6-tetrahydropyri-dines, which have previously been shown to possess anti-inflammatory activities, were built using BIOMEDCAche 5.0 software program. In addition, the three dimensional structures of some of the inactive ones were similarly generated. The conformational analysis, molecular and electronic structures were examined by molecular mechanics and quantum mechanics calculations. The primary objective was to clarify the effects of physicochemical properties of substituents on activity, since the exact role of the substitution pattern on the phenyl ring is uncertain. In addition, the experimental log P values did not appear to have any influence on the anti-inflammatory potencies of these compounds, since compounds having differing lipid solubilities are equiactive. We found that strongly electron-donating group, such as the para-substituted methoxy group, detracts from activity. The conformational analysis indicated that the 4-ethyl derivative had the lowest energy conformation. Except for compound 1, which showed the lowest surface volume, compounds 2-9 had nearly similar surface volumes.     

In vitro antioxidant activity and scavenging effects of Cinnamomum verum leaf extract assayed by different methodologies.

The free radical scavenging capacity and antioxidant activities of the methanolic extract of Cinnamomum verum leaf (CLE) were studied and compared to antioxidant compounds like trolox, butylated hydroxyl anisole, gallic acid and ascorbic acid. The CLE exhibited free radical scavenging activity, especially against DPPH radical and ABTS radical cation. They also exhibited reducing power and metal ion chelating activity, along with hydroxyl radical scavenging activity. The peroxidation inhibiting activity of CLE recorded using the linoleic acid emulsion system, showed very good antioxidant activity.     

Additional antilipoperoxidant activities of alpha-tocopherol and ascorbic acid on membrane-like systems are potentiated by rutin.

The effects of alpha-tocopherol, ascorbic acid and rutin on peroxidative processes were studied in xanthine-xanthine oxidase system, linoleic acid ufasomes and human erythrocyte membranes. In these three systems, tested compounds scavenge superoxide anion radicals or inhibit lipid peroxidation in a concentration-dependent manner, and it was shown that rutin was the most potent radical scavenger, followed by ascorbic acid and alpha-tocopherol. An important antilipoperoxidant activity was observed when these compounds were tested in combination, demonstrating that a dose-dependent interaction occurs. Water-soluble (rutin and ascorbic acid) as well as lipid-soluble (tocopherol) antioxidants are involved in the protection of polyunsaturated fatty acids constituting the ufasome or erythrocyte ghosts. When these compounds are used in combination, an additive effect is observed with alpha-tocopherol and ascorbic acid or rutin, while a supra-additive effect (synergism) is noted with ascorbic acid and rutin. Results obtained with the triple combination alpha-tocopherol-ascorbic acid-rutin show that an increase in superoxide radical scavenging activities or in lipid peroxidation inhibition is possible after the addition of a third antioxidant, as compared with the protective effects produced by the double combination of these compounds. This interaction takes place not only in homogeneous aqueous solutions, but also in ufasome or erythrocyte ghost preparations. It is suggested that ascorbic acid and rutin interacts with tocopherol at the surface of or the interface with the membrane, and that rutin simultaneously interacts with ascorbic acid.     

Synthesis and antibacterial,antifungal activities of some 2<Emphasis Type="Italic">r</Emphasis>,4<Emphasis Type="Italic">c</Emphasis>-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazones

A series of biologically active seven 2r,4c-diaryl-3-azabicyclo[3.3.1]nonan-9-one-4-aminobenzoyl hydrazone derivatives have been synthesized in good yield. The structures of compounds have been established on the basis of IR, ¹H, ¹³C NMR, and elemental analysis. The structure–activity relationships (SAR) have been studied by screening of antimicrobial activity over a representative panel of bacterial and fungal strains using two-fold serial dilution method. All these synthesized compounds exhibited significant activities against all bacterial and fungal strains.     

Synthesis and antimicrobial and antioxidant activities of simple saccharin derivatives with N-basic side chains

A new class of N-basic side chains was obtained from 2,3-dihydro-2H-3-oxobenzo[d]isothiazole and aliphatic or aromatic aldehydes. Secondary amines (morpholine, N-methylpiperazine and ethyl isonipecotate) afforded tertiary N-basic side chains (4–6), while dibasic secondary amines (such as piperazine) gave bis-tertiary N-basic side chains (2). On the other hand, the use of mono- or dibasic primary amines namely; aniline, anisidine, phenyl hydrazine, o-hydroxy benzoic acid hydrazide, hydrazine hydrate, and ethylenediamine (instead of secondary amines) afforded secondary N-basic side chain as mono component or as bis component 7a-c, 9a-c, 11 and 12a-c. In addition, secondary Mannich base was synthesized via Michael addition to the corresponding aldimine. The new compounds were investigated for antioxidant and antimicrobial activities. Compounds 2, 7c and 12a exhibited significant antimicrobial activity, whereas compounds 7a, 7b, 9b, 9c and 11 exhibited high antioxidant activity as compared to ascorbic acid, These compounds showed the best protective effect against DNA damage induced by bleomycin.     

Synthesis and comparison of antioxidant properties of indole-based melatonin analogue indole amino Acid derivatives

Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin -based analogue indole amino acid and N-protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.     

Screening chemical composition and in vitro antioxidant and antimicrobial activities of the essential oils from Origanum syriacum L. growing in Turkey

In the present study, essential oil from the leaves of Syrian oreganum [Origanum syriacum L. (Lauraceae)] grown in Turkish state forests of the Dortyol district, Turkey, was obtained by steam distillation. The chemical composition of oil was analysed by GC and GC-MS, and was found to contain 49.02% monoterpenes, 36.60% oxygenated monoterpenes and 12.59% sesquiterpenes. The major components are as follows: gamma-terpinene, carvacrol, p-cymene and beta-caryophyllene. Subsequently, the reducing power, antioxidant and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activities of the essential oil were studied. The reducing power was compared with ascorbic acid, and the other activities were compared with 2,6-di-tert-butyl-4-methyl phenol (BHT, butylated hydroxytoluene). The results showed that the activities were concentration dependent. The antioxidant activities of the oil were slightly lower than those of ascorbic acid or BHT, so the oil can be considered an effective natural antioxidant. Antimicrobial activities of the essential oil from the leaves of Origanum syriacum was also determined on 16 microorganisms tested using the agar-disc diffusion method, and showed antimicrobial activity against 13 of these.     

Antimicrobial, analgesic, DPPH scavenging activities and molecular docking study of some 1,3,5-triaryl-2-pyrazolines

A series of 1,3,5-triaryl-2-pyrazolines 2a–g were synthesized by the reaction of 4,4′-disubstituted chalcone with phenyl hydrazine. All these compounds were characterized by NMR, IR and mass spectral and single crystal XRD data. All the synthesized products were screened for their in vitro antimicrobial, analgesic and antioxidant properties. The docking studies were carried out for these compounds against the active site of methionyl-tRNA synthetase (metRS). Some of the tested compounds exhibited significant antimicrobial, analgesic, DPPH scavenging activities and molecular binding.     

Synthesis, evaluation and docking studies on steroidal pyrazolones as anticancer and antimicrobial agents

A series of new steroidal pyrazolones have been synthesized, characterised and evaluated for their in vitro anticancer activity. They were tested against five cancer (SW480, HepG2, A549, HeLa and HL-60) cell lines. The synthesized compounds showed high selectivity and compound 4 showed the strongest inhibitory activity against human SW480 (IC₅₀ = 11.67 μmol L^?1). In addition, the synthesized compounds were tested for their antimicrobial activity by disc diffusion assay and MIC by broth micro dilution method against Gram-positive, Gram-negative strains of bacteria as well as fungus strains and we found a correlation between the observed and predicted antimicrobial activities. Docking studies were performed to investigate the hypothetical binding mode of the target compounds. This study provided a new molecular scaffold for the further development of anticancer as well as antimicrobial agents.     

Synthesis, physicochemical properties, antimicrobial and antioxidant studies of pyrazoline derivatives bearing a pyridyl moiety

A series of new pyrazoline compounds bearing a pyridyl moiety (4a–i) were synthesized by condensing appropriate chalcones with hydrazine hydrate and tested for antimicrobial and antioxidant activities. According to in vitro antimicrobial activity against Bacillus subtilis, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas aeruginosa, Aspergillus niger and Penicillium chrysogenum and antioxidant activity by DPPH method, the compounds 4a, 4d, 4i and 4e, 4f, 4h showed maximum antimicrobial and antioxidant activities, respectively. Physiochemical properties and Lipinski’s ‘Rule of Five’ analysis predicted higher intrinsic quality of the synthesized compounds and revealed that these compounds have good bioavailability and druglikeness properties.     

Synthesis and antioxidant activity of pyrazolyl-oxazolines/thiazolines and isoxazolyl-oxazolines/thiazolines

A new class of pyrazolyl/isoxazolyl-oxazolines and thiazolines were synthesized from E-arylsulfonylethenesulfonylacetic acid methyl ester and tested for antioxidant activity. Among the tested compounds, 14b exhibited excellent antioxidant activity when compared with the standard ascorbic acid.     

Microwave-assisted synthesis and bioevaluation of some semicarbazones

In continuation to our efforts in finding potential therapeutic agents, a variety of biologically significant semicarbazones were synthesized by the reaction of different carbonyl compounds with phenyl semicarbazides through microwave irradiation. Initially, 18 semicarbazones were studied for their antimicrobial, antitumor, and antioxidant potential. None of the tested compounds showed any antibacterial activity; however, some compounds showed significant antifungal activity. Interestingly, all compounds showed antitumor activity when tested against tumors grown on potato discs. These compounds were also tested for their effect on OH radical-induced oxidative DNA damage. All the compounds showed DNA protection to varying extent. Based on the promising results of antitumor and antioxidant activities, another set of 24 semicarbazones was synthesized, and all of these semicarbazones were evaluated for their antioxidant potential. The results showed that the semicarbazones derived from 2-nitrobenzaldehyde and acetophenone were the most active 2,2-diphenyl-1-picrylhydrazyl 9 (DPPH) free radical scavengers. The overall results have led to the identification of some interesting compounds which seem to have great potential to be developed into effective anticancer drugs.     

Thiazolyl and isothiazolyl azomethine derivatives with anti-inflammatory and antioxidant activities

Several thiazolyl/benzothiazolyl/benzo[d]isothiazolyl Schiff bases and hydrazones have been tested as anti-inflammatory agents and five new compounds have been synthesized. The anti-inflammatory activity was examined in vivo using the carrageenin induced mice paw edema test (inhibition 16.3-64%). The compounds were tested for antioxidant activity as hydroxyl scavengers and for their ability to interact with the stable free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Both anti-inflammatory and antioxidant activities depended on some structural characteristics of the synthesized compounds.     

Synthesis of some novel oxazolidinone-thiazole hybrids as potential antimicrobial,antioxidant and UV mediated DNA damage protecting agents

In search of a new class of biologically active agents, some novel oxazolidinone-thiazole hybrids 4a–m have been synthesized and characterized on the basis of a combined use of infrared, NMR (¹H, ¹³C) spectroscopy, mass spectrometry and elemental analysis. All compounds were evaluated for their antimicrobial, antioxidant and ultraviolet mediated DNA damage protective activity. Among the series, compound 4i emerged as the most potent antimicrobial agent, particularly, against Bacillus subtilis, Candida albicans and Saccharomyces cerevisiae in comparison to the standard drugs, Ciprofloxacin (antibacterial) and Amphotericin-B (antifungal). Other promising antimicrobial agents including the compounds 4f–h. In addition, all compounds 4a–m were found to show very high DNA damage protecting ability under ultraviolet irradiation. The antioxidant study revealed that the compounds 4d and 4j were found as the most potent antioxidants as compared to ascorbic acid, a reference compound considered in the study.