Synthesis and evaluation of in vitro antioxidant capacities of some benzimidazole derivatives

New, except 1d, melatonin analogue benzimidazole derivatives were synthesized and characterized in the present study. The potential role of melatonin as an antioxidant by scavenging and detoxifying ROS raised the possibility that compounds that are analogous to melatonin can also be used for their antioxidant properties. Therefore the antioxidant effects of the newly synthesized compounds were investigated in vitro by means of their inhibitory effect on hydrogen peroxide-induced erythrocyte membrane lipid peroxidation (EMLP) and on various erythrocyte antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT) and glucose-6-phosphate dehydrogenase (G6PD). The synthesized benzimidazole derivatives showed remarkable antioxidant activity in vitro in the H₂O₂-induced EMLP system. Furthermore their effects on various antioxidant enzymes are discussed and evaluated from the perspective of structure- activity relationships.     

Synthesis, antifungal and antioxidant screening of some novel benzimidazole derivatives

Some novel benzimidazole derivatives were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) level, ethoxyresorufin O-deethylase (EROD) and antifungal activities were determined. A significant decrease in male rat liver microsomal LP level was noted by compounds 4c (52%), 4e (58%) and 4h (43%) at 10(-3) M concentration. Compounds 4c (100.0%), 4h (100.0%), 5c (98.0%) and 5h (100.0%) inhibited the microsomal ethoxyresorufin O-deethylase (EROD) enzyme activity better than that of the specific inhibitor caffeine (85%). Among these compounds, only compounds 4b and 4h exhibited moderate activity against C. albicans whereas the others had weak effects.     

Synthesis,antifungal and antioxidant screening of some novel benzimidazole derivatives

Some novel benzimidazole derivatives were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) level, ethoxyresorufin O-deethylase (EROD) and antifungal activities were determined. A significant decrease in male rat liver microsomal LP level was noted by compounds 4c (52%), 4e (58%) and 4h (43%) at 10^{? 3} M concentration. Compounds 4c (100.0%), 4h (100.0%), 5c (98.0%) and 5h (100.0%) inhibited the microsomal ethoxyresorufin O-deethylase (EROD) enzyme activity better than that of the specific inhibitor caffeine (85%). Among these compounds, only compounds 4b and 4h exhibited moderate activity against C.albicans whereas the others had weak effects.     

Synthesis and antioxidant properties of novel benzimidazole derivatives

Some novel benzimidazole derivatives carrying thiosemicarbazide and triazole moieties at the N1 position were synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels determined by measuring the formation of 2-thiobarbituric acid reactive substance. The free radical scavenging properties of the compounds were also examined in vitro by determining the capacity to scavenge superoxide anion formation and the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The compounds showed a significant effect in the above tests except to scavenge superoxide anion formation.     

Synthesis and in vitro cytotoxicity evaluation of some fluorinated hexahydropyrimidine derivatives

A series of trifluoromethylated hexahydropyrimidine and tetrahydropyrimidine derivatives were synthesized and their in vitro cytotoxic activities were determined in colon cancer cell line (COLO 320 HSR). Compounds 4f, 4g, 4k, 5, and 7 proved to be the most active in this series of compounds. They represent promising new leads for the development of highly potent and selective anticancer compounds. All the compounds are lipophilic due to the trifluoromethyl group, and are thus expected to penetrate the membrane in appreciable concentration.     

Synthesis,antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

A series of 2-arylbenzimidazole derivatives (3a–3p and 4a–4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O₂^?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC₅₀ = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H₂O₂-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.     

Synthesis,molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors

In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC₅₀ values of 1.72 ± 0.12 µM, 1.92 ± 0.28 and 0.98 ± 0.07 µM, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms.     

Synthesis and evaluation of in vitro anticancer activity of some novel isopentenyladenosine derivatives

The present study describes the synthesis, the characterization and the evaluation of some derivatives of N⁶-isopentenyladenosine on T24 human bladder carcinoma cells. In particular we have modified the hydroxyl groups in the ribose moiety, the position of the isopentenyl chain in the purine ring and the base moiety. The structures of the compounds were confirmed by standard studies of NMR, MS and elemental analysis. We here show that only two derivatives, 1-(3-methyl-2-butenylamino)-9-(3′-deoxy-β-d-ribofuranosyl)-purine hydrobromide and 2-amino-6-(3-methyl-2- butenylamino)-9-(β-d-ribofuranosyl)-purine, inhibit the growth of T24 cells, although to a lower extent than N⁶-isopentenyladenosine. We conclude that the integrity of ribosidic and purine moiety and the N⁶ position of the chain are essential for maintaining the antiproliferative activity.     

Synthesis and antioxidant capacities of hydroxyl derivatives of cinnamoylphenethylamine in protecting DNA and scavenging radicals

Cinnamoylphenethylamine (CNPA) derivatives including feruloylphenethylamine (FRPA), caffeoylphenethylamine (CFPA), cinnamoyltyramine (CNTA), feruloyltyramine (FRTA) and caffeoyltyramine (CFTA) were synthesized in order to investigate the influence of the number and position of hydroxyl group on Cu(2+)/glutathione (GSH) and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. The radical-scavenging properties of these CNPA derivatives were also evaluated by trapping 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonate) cationic radical (ABTS(+?)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and galvinoxyl radical. In addition, these CNPA derivatives were tested by linoleic acid (LH)-β-carotene-bleaching experiment. The chemical kinetic was employed to treat the results from AAPH-induced oxidation of DNA and gave the order of antioxidant ability as CFTA > CFPA > FRTA > FRPA. CFTA and CFPA also possessed high abilities to inhibit Cu2(+)/GSH-mediated degradation of DNA, whereas FRPA and FRTA can protect LH against the auto-oxidation efficiently. Finally, CFPA and FRPA exhibited high activity in trapping ABTS(+?), DPPH and galvinoxyl radicals. Therefore, the cinnamoyl group bearing ortho-dihydroxyl or hydroxyl with ortho-methoxyl benefited for CNPA derivatives to protect DNA, while hydroxyl in tyramine cannot enhance the radical-scavenging abilities of CNPA derivatives.     

Screening and evaluation of antioxidant activity of some pyridazine derivatives

Antioxidants are compounds that can delay, inhibit, or prevent the oxidation of materials that can be oxidized by scavenging free radicals and help in diminishing oxidative stress. They belong to different chemical classes. Recently there are studies related to pyridazinone derivatives for their antioxidant activities. Since there are evidences implicates reactive oxygen species and nitric oxide as mediators of inflammation and/or tissue damage in inflammatory and arthritic disorders it was though that compounds that have both antioxidant and anti-inflammatory activities would have been essential for the inflammatory diseases. Based on these findings a series of 2H-pyridazine-3-one and 6-chloropyridazine analogues that have anti-inflammatory activity was tested in vitro on superoxide formation and effects on lipid peroxidation were determined against alpha-tocopherol. Most of the compounds have strong inhibitory effect on superoxide anion (between 84% - 99%) at 10(- 3) M concentration. In addition, these compounds showed similar activity to alpha-tocopherol at 10(- 3) M concentrations.     

Synthesis,characterization, antioxidant power and acute toxicity of some new azo-benzamide and azo-imidazolone derivatives with in vivo and in vitro antimicrobial evaluation

In this research paper, a stepwise chemical reaction was conducted to synthesize and develop of a new potent azo-oxazolone, which was used as prototypical molecule for production of two series of azo-benzimide (5a–j) and azo-imidazolone (6a–j). FT-IR, ¹H NMR, ¹³C NMR and CHN analysis were used for the structural elucidation. The high biological efficiency of newly obtained compounds was confirmed by in vitro antioxidant efficacy and in vitro antimicrobial activity against gram-positive and gram-negative bacteria via disc diffusion and tube dilution techniques. In addition, in vivo anti-microbial activity of some of the synthesized compounds was determined by using burnt rats which infected by Staphylococcus aureus. Tested compounds have shown high anti-microbial activity and wound healing in comparison to ucederm as a control. In vivo acute toxicity was carried out by up and down method for the compounds 4, 5d and 6d. The limited test dose was 2000 mg/kg, while the maximum tolerated dose was 5000 mg/kg which has administered no lethality recorded.     

Synthesis and biological evaluation of some dibenzofuran-piperazine derivatives

In the present paper, a novel series of dibenzofuran-piperazine derivatives were synthesized via the treatment of N-(2-methoxy-3-dibenzofuranyl)-2-chloroacetamide with substituted piperazine derivatives. The chemical structures of the compounds were elucidated by ¹H NMR, ¹³C NMR, mass spectral data; elemental analysis and HPLC analysis. Each derivative was evaluated for antiplatelet activity and anticholinesterase activity. Compound 2?m with 2-furoyl moiety exhibited high percentage inhibition as much as standard drug aspirin on arachidonic acid (AA)-induced platelet aggregation. None of the compounds presented significant inhibitor effect on collagen-induced platelet aggregation. Furthermore, the anticholinesterase activity of the compounds was determined and they did not show promising inhibitor activity compared with standard drug donepezil.     

Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities

A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC₅₀ = 58.43 μM) as well as for SIRT2 (IC₅₀ = 45.12 μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure–activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.     

Synthesis and in vitro antitumor evaluation of honokiol derivatives

Honokiol is a natural bioactive neolignan and has been widely researched and structural modified as an anticancer agent. In this paper, 18 honokiol derivatives were synthesized and investigated for their antitumor activity. Among these, the promising compound 5a exhibited much higher anti-proliferative activity with IC₅₀ value of 10.41 μM. Transwell assays showed that 5a could significantly inhibit the invasion and migration of I-10 cells at 2.5 μM, which was further confirmed by the western blotting experiments with down-regulation of the HIF-1α and its associated downstream proteins MMP-2 and MMP-9. Overall, these results provided useful suggestion for further structural optimization of honokiol derivatives.     

Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole

By combining the structural features of quinazoline and benzimidazole, new hybrid regioisomeric molecules with substituted primary amines have been synthesized. Evaluation of these molecules over 60 cancer cell line panel has identified three molecules as most potent anticancer agents. Compound 10 showed ten and eleven folds more activity than respective quinazoline and benzimidazole class of compounds with GI₅₀ value of 1.64 μM. Compound 11 (GI₅₀ value of 0.81 μM) showed almost twenty and twenty-two fold more activity than quinazoline and benzimidazole analogue, respectively while compound 12 (GI₅₀ value of 4.52 μM) has four fold more activity than quinazoline and benzimidazole analogue. In vitro evaluation of compound 11 exhibited remarkable anticancer activity towards colon cancer cell lines and prostate cancer cell lines at five dose concentrations with GI₅₀ values of 0.34 and 0.31 μM, respectively.     

Synthesis and antiviral activity against Coxsackie virus B3 of some novel benzimidazole derivatives

Some benzimidazole derivatives were synthesized and evaluated for their antiviral properties. Compounds 20 and 21 showed potent selective activity against Coxsackie virus B(3) in VERO cells. Some structure-activity relationships were discussed.     

Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators

Design, synthesis and structure-activity relationships of benzimidazole derivatives as activators of the AMP-activated protein kinase (AMPK) are presented in this paper. AMPK is the central component of a protein kinase cascade that plays a key role in the regulation of energy balance. Once activated, AMPK initiates a series of responses that are aimed at restoring the energy balance of the cell and recent studies have indicated that AMPK plays an important role in regulation of the whole-body energy metabolism. The following study based on the lead compound S27847 involved modification of three regions of this compound. Preliminary structure-activity relationships are being described.     

Synthesis,in vitro antiproliferative activity and kinase profile of new benzimidazole and benzotriazole derivatives

Protein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as a promising target in anticancer therapy. New derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) bearing azide or substituted triazole groups were synthesized. Their influence on the activity of human recombinant CK2α and cytotoxicity against normal and cancer cell lines were evaluated. TBBi derivatives with triazole substituted with carboxyl substituent (7 and 10) exhibited the most potent inhibitory activity against CK2 with K_i value in the range of 1.96–0.91 μM, respectively. New TBBi derivatives 2, 3, 5 and 9 have demonstrated the EC₅₀, in the range of 12–25 μM and 13–29 μM respectively towards CCRF-CEM and MCF-7 cells. Derivatives TBBi decreased viability of cancer cells more efficiently than BALB cells and the biggest differences were observed for the azide substituted compounds 3 and 5. The effect of the most active compounds on the activity of eight off-target kinases was evaluated. Inhibitory efficiency of CK2-mediated p65 phosphorylation was demonstrated for the TBBi and compound 12.     

Synthesis and biological evaluation of some new pyridazinone derivatives

A series of pyridazinone derivatives (19–34) were synthesized with an aim to synthesize safer anti-inflammatory agents. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation (LPO) actions. The percentage inhibition in edema at different time intervals indicated that compounds 20, 26, 28 and 34 exhibited good anti-inflammatory potential, comparable with that of ibuprofen (85.77%) within a range of 67.48–77.23%. The results illustrate that 5-(4-fluoro-benzyl)-3-(4-chloro-phenyl)-1,6-dihydro-6-pyridazinone (26) and 5-(4-chloro-benzyl)-3-(4-chloro-phenyl)-1,6-dihydro-6-pyridazinone (20) showed best anti-inflammatory activity. Furthermore, activity is more in case of chloro substitution as compared with methyl-substitution. The compounds synthesized were also evaluated for their ulcerogenic and LPO action and showed superior gastrointestinal safety profile along with reduction in LPO as compared with that of the ibuprofen.