Zeynep Ates-Alagoz

Antimicrobial activities of some tetrahydronaphthalene-benzimidazole derivatives.

Novel retinoid derivatives containing a benzimidazole moiety were synthesized and tested for their antimicrobial activity. Their antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Candida krusei and Candida albicans were evaluated. While some of the compounds exhibited moderate activity against MRSA, S. aureus, E. faecalis, C. krusei and C. albicans, none of the compounds showed activity against E. coli and P. aeruginosa.

Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene fragments

Some 6-fluoro-5-substituted-benzimidazole derivatives in which indole and 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene groups were attached to the 2-position of the benzimidazole ring were synthesized and tested for antioxidant properties in vitro. Almost all the synthesized compounds at the 10− 3 M concentrations showed superoxide anion scavenging activity. Compounds 5, 3, 9, 4, 17 and 13 have strong inhibitory effects on superoxide anion formation (98%, 93%, 91%, 88%, 85% and 81%, respectively) at 10− 3 M concentration and these results are better than 30 IU of superoxide dismutase (SOD) (76%). Compound 11 is the most effective scavenger of 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable free radical at 10− 3 M (61%) concentration.

A Comparative Study: Evaluation of Antioxidant Activity of Melatonin and Some Indole Derivatives

To understand antioxidant activity and the role played by melatonin, we have designed and tested several new compounds. We present the results in terms of structure-activity relationships, focusing on the lack of the methoxy group and the influence of the amide side chain. Antioxidant activity of melatonin and some new melatonin analogue indole derivatives were investigated, using lipid peroxidation and superoxide anion radical scavenger activity assays, in rat liver tissue homogenate. Most of the compounds were found to be very potent inhibitors of malondialdehyde (MDA) formation at 10−3M. Inhibition rates ranged from 75-44 %. However, no significant inhibitory effect was obtained on superoxide anion formation. Consequently, it can be concluded that these compounds exhibit important LP activity compared to melatonin.

Synthesis and analytical evaluation by voltammetric studies of some new indole-3-propionamide derivatives

Some biologically important and melatonin-related indole-3-propionamide derivatives were synthesized. The compounds synthesized were analyzed and characterized first by NMR and mass spectrometry and then investigated by analytical voltammetric techniques. Based on this study a simple, rapid and sensitive voltammetric method was developed for the determination of the indole derivatives that are readily oxidized at the carbon-based electrodes. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode. The characteristics of the corresponding electrode reaction were discussed.

Synthesis and antimicrobial evaluation of some new substituted purine derivatives.

A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolate), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. 6-[(N-phenylaminoethyl)amino]-9H-purine (12) which has no substitution at N-9 position and 9-cyclopentyl-6-[(4-fluorobenzyl)amino]-9H-purine (24) exhibited excellent activity against C. albicans with MIC 3.12 microg/mL. These compounds displayed better antifungal activity than that of standard oxiconazole. Furthermore, compound 22 carrying 4-chlorobenzylamino group at the 6-position of the purine moiety exhibited comparable antibacterial activity with that of the standard ciprofloxacin against both of the drug-resistant bacteria (MRSA, standard and clinical isolate).

Antioxidant Activities of Retinoidal Benzimidazole Or Indole Derivatives in In Vitro Model Systems

The antioxidants and antioxidant enzyme systems belong to the major protective systems of the organism. The use of retinoic acid in many animal models of carcinogenesis has also suggested that its action may depend on its antioxidant activity. Retinoids have been shown to function as effective antioxidants by inhibiting microsomal lipid peroxidation. The importance of antioxidants for the maintenance of health and for protection from oxidative stressinduced damage places them in the forefront of mechanistic approaches to genetically originated diseases related to retinoids. It is well known that cellular and subcellular membranes are susceptible to lipid oxidation because of their relatively high concentration of polyunsaturated fatty acids and their close proximity to oxygen, transition metals and peroxidases. Therefore, there has been a great deal of interest in the study of reactive oxygen species (ROS) which are associated with arteriosclerosis, nephritis and carcinogenesis. Antioxidants scavenge and prevent the formation of free radicals so they are highly important for the treatment of these kinds of diseases. For this reason, antioxidant properties of retinoidal benzimidazole or indole derivatives have been investigated in this review.

Genotoxicity studies of tetrahydro-naphthalenebenzimidazole/ thiazolidinedione as retinoid derivatives / Tetrahidro-naftalen-benzimidazol/tiyazolidindion retinoid türevlerinin genotoksisitesi

Abstract Objective: Mutagenicity is an undesirable side effect of clinically prescribed drugs, thus raises the question of their potential carcinogenicity. Taking into account that nitro compounds are known for their genotoxicity, it will be considerable interest to assess the genotoxic activities of the benzimidazole/thiazolidinedione retinoid derivatives. For this reason, the present study reports the genotoxicity of previously synthesized benzimidazole/ thiazolidinedione-retinoid derivatives (Ates-Alagoz and Buyukbingol, 2001; Ates-Alagoz et. al., 2009) by the umu-microplate test system. Methods: In this study, since this derivates involve nitro groups, makes advantageous the use of the umu-test, using NM2009 and NM1011 strains especially designed for detecting the mutagenicity of nitro compounds. Two bacterial strains Salmonella typhimurium NM1011 and S. typhimurium NM2009, expressing high levels of nitroreductase (NR) and O-acetyltransferase (O-AT) respectively, were used in the tests. Chlorophenol red-β-D-galactopyranoside (CPRG), O-nitrophenyl- β-D-galactopyranoside (ONPG) were used as substrate in the enzyme assays along with a well-known genotoxic nitro compound, 4-nitroquinoline 1-oxide (4NQO), as the positive control in the test. Results: Benzimidazole/ thiazolidinedione-retinoids that contain NO2 group with different position on benzene ring showed no genotoxicity in both strains with both substrates. However, using CPRG as the colorimetric substrate resulted in stronger activity than using ONPG in test conducted in both strains with all compounds. Although the β-galactosidase activities with using CPRG were three fold higher than ONPG, parallel results were obtained for both substrates and strains with all compounds tested. For all compounds, the induction of umuC gene expression was found to be almost the same for the strains that overexpress nitroreductase and O-acetyltransferase. Conclusion: None of the derivatives showed genotoxic effects, a very important data, making them a potential drug candidate. Ozet Amac: Klinikte, mutajenite ilacların istenmeyen yan etkilerinden birisidir, nitrolu bileşikler de genotoksik etkileriyle bilindikleri icin, bu calışmada ilac etken maddesi olarak tasarlanmış ve daha onceden sentezlenmiş benzimidazole/ tiyazolidindion retinoid turevlerinin genotoksik potansiyelleri, umu-mikroplak test sistemi ile değerlendirilmiştir. Metod: Umu-mikroplak test sistemi ozel olarak nitrolu bileşiklerin mutajenitesini saptamak icin tasarlanmıştır. Benzimidazol/ tiyazolidindion retinoid turevleri de nitro grubu icermektedir, bu nedenle calışmamızda bu test sistemi secilmiştir. Hata meyilli onarım sistemini (SOS) indukleme aktivitelerinin değerlendirildiği umu-mikroplak test sisteminde, nitrolu bileşiklere hassas olarak geliştirilmiş, NR (nitroreduktaz) enzimini normalden fazla ifade eden Salmonella typhimurium NM1011 ve O-At (O-asetiltransferaz) enzimini normalden fazla ifade eden S. typhimurium NM2009 suşları kullanılmıştır. Enzim test ortamında klorofenol-red-β-D-galaktopiranosid (CPRG) ve o-nitrofenil-β-D-galaktopiranosid (ONPG) substrat olarak ve genotoksik ajan olduğu bilinen 4-nitroquinoline 1-oxide (4NQO) de pozitif kontrol olarak kullanılmıştır. Bulgular: Benzen halkasının farklı pozisyonlarında nitro grubu iceren Benzimidazol/tiyazolidindion retinoid turevleri umu-mikroplak test sisteminde her iki suş ve her iki substratla genotoksik etki gostermemiştir. Test edilen maddelerin tumunde benzer sonuclar elde edilmiştir. Tumu icin, her iki suş ve substratla, umuC geninin ekspresyonunun induksiyonu hemen hemen aynı bulunmuştur. Sonuc: Retinoid turevlerinin hicbiri umu-mikroplak test sisteminde genotoksik etki gostermemiştir. Bu sonuc, ilac adayı olarak değerlendirilmelerinde cok onemli bir veridir.

Syntheses and Pharmacological Evaluations of Novel N-substituted Bicyclo-heptan-2-amines at NMDA Receptors

Several novel norcamphor (bicycloheptane)‐based compounds were designed and synthesized as non‐competitive N‐methyl‐d‐aspartate receptor antagonists at the phencyclidine binding sites. The heterocyclic ring was also varied to examine piperidine, pyrrolidine, and morpholine groups. We examined pharmacological activities of these compounds in vitro (binding studies) and in vivo (maximal electroshock test). Pharmacological evaluations revealed one of the compounds, 5a, to be a good lead, exhibiting moderate binding at N‐methyl‐d‐aspartate receptors (IC50 = 7.86 μm; Ki = 5.28 μm), maximal electroshock neuroprotection activity at 100 mg/kg and acceptable toxicity profile.

Syntheses and Pharmacological Evaluations of Novel N-Substituted Bicyclo-Heptane-2-amines at N-Methyl-d-Aspartate Receptors: Syntheses and Pharmacological Evaluations of NMDA Receptor Antagonists

Several novel norcamphor (bicycloheptane)‐based compounds were designed and synthesized as non‐competitive N‐methyl‐d‐aspartate receptor antagonists at the phencyclidine binding sites. The heterocyclic ring was also varied to examine piperidine, pyrrolidine, and morpholine groups. We examined pharmacological activities of these compounds in vitro (binding studies) and in vivo (maximal electroshock test). Pharmacological evaluations revealed one of the compounds, 5a, to be a good lead, exhibiting moderate binding at N‐methyl‐d‐aspartate receptors (IC50 = 7.86 μm; Ki = 5.28 μm), maximal electroshock neuroprotection activity at 100 mg/kg and acceptable toxicity profile.

Synthesis and structure of 2-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalene)]-5-benzimidazole ethylcarboxylate monohydrate

As part of a program investigating the conformations of potential anticarcinogens and antioxidants, the structure of the title compound C24H28N2O2·H2O is reported. The monohydrate crystallizes in the monoclinic space group P2/c with unit cell parameters a = 16.184(1),b = 7.937(1), c = 16.968(1), β = 92.788(7)°, and Z = 4. The benzimidazole and tetrahydrotetramethylnaphthalene ring systems are inclined to one another by approximately 26°. The water molecule plays an important role in the crystal structure by hydrogen bonding to different functional groups of three organic moieties. Additional crystal stabilization is dueto π–π stacking of benzimidazole rings.