Sibel Suzen

Recent studies of aldose reductase enzyme inhibition for diabetic complications.

Aldose reductase [ALR2; EC 1.1.1.21], a key enzyme of polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol (Sorbitol pathway), and an excessive accumulation of intracellular sorbitol found in various tissues of diabetic animals and in cells cultured under high glucose conditions has been proposed to be an important factor for the pathogenesis of diabetic complications. The only strategy shown to be consistently beneficial in the treatment of diabetic complications is meticulous control of blood glucose. However, aldose reductase (AR) enzyme inhibition is becoming one of the therapeutic strategies that have been proposed to prevent or ameliorate long-term diabetic complications. Therefore, AR inhibitors (ARIs) hold promise for reducing metabolic nerve injury, but further study is needed. On the other hand, there is strong evidence to show that diabetes is associated with increased oxidative stress. However, the source of this oxidative stress remains unclear. This relationship between diabetic complications and free radical production was also under investigation. The studies suggest that hydroxyl radical is indirectly inhibited by ARIs resulting from decreasing polyol levels and hydroxyl radical formation is related to the early stages of diabetic complications, possibly via the Fenton reaction involving H(2)O(2) produced from the activated polyol pathway. Therefore, it is proposed that hydroxyl radical may accelerate damage to the cell membranes resulting from polyol accumulation. The search for specific inhibitors of AR enzyme has still become a major pharmaceutic challenge, though a number of AR inhibitors have so far been assessed for diabetic complications.

Antioxidant Activities of Synthetic Indole Derivatives and Possible Activity Mechanisms

Indole derivatives constitute an important class of therapeutical agents in medicinal chemistry including anticancer, antioxidant, antirheumatoidal, aldose reductase inhibitor, and anti-HIV agents. Reactive oxygen species are constantly generated in the human body and are involved in various physiologically important biological reactions. However, high levels of free radicals can cause damage to biomolecules such as lipids, proteins, and DNA within cells. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinsons disease, Alzheimers disease, Huntingtons disease, epileptic seizures, stroke, and as a contributor to aging and some types of cancer. Indolic compounds are very efficient antioxidants, protecting both lipids and proteins from peroxidation and it is known that the indole structure influences the antioxidant efficacy in biological systems. Due to its free radical scavenger and antioxidant properties, synthesis of indole derivative compounds are under investigation to determine which exhibit the highest activity with the lowest side effects. Epidemiological studies have been strongly suggesting that antioxidants can decrease the rate of many diseases. However, more clinical studies are required to determine the efficacy and safety of these compounds. This chapter gives another perspective on antioxidant activities of synthetic melatonin analogues.

Investigation of the in vitro antioxidant behaviour of some 2-phenylindole derivatives: discussion on possible antioxidant mechanisms and comparison with melatonin

Oxidative stress has been implicated in the development of many neurodegenerative diseases and also responsible from aging and some cancer types. Indolic compounds are a broad family of substances present in microorganisms, plants and animals. They are mainly related to tryptophan metabolism, and present particular properties that depend on their respective chemical structures. Due to free radical scavenger and antioxidant properties of indolic derivatives such as indolinic nitroxides and melatonin, a series of 2-phenyl indole derivatives were prepared and their in vitro effects on rat liver lipid peroxidation levels, superoxide formation and DPPH stable radical scavenging activities were determined against melatonin, BHT and α-tocopherol. The compounds significantly inhibited (72–98%) lipid peroxidation at 10− 3 M. These values were similar to that observed with BHT (88%). Possible structure–activity relationships of the compounds were discussed.

Electroanalytical evaluation and determination of 5-(3'-indolyl)-2-thiohydantoin derivatives by voltammetric studies: possible relevance to in vitro metabolism

Some biologically important indolylthiohydantoin derivatives were investigated electroanalytically by voltammetric determination. Based on this study, a simple, rapid, sensitive and validated voltammetric method was developed for the determination of the indolylthiohydantoin derivatives that are readily oxidized at carbon-based electrodes. Due to the similarity between electrochemical and biological reactions it can be assumed that the oxidation mechanisms taking place at the electrode and in the body share similar principles. The oxidative behavior of the indole derivatives was studied as a function of pH at a glassy carbon electrode in different buffer media. The characteristics of the corresponding electrode reaction were discussed. The studied molecules are extensively metabolized in vivo, mainly through oxidative processes and we assume that the oxidation of the indolic compounds occurs on the nitrogen atom in the indole ring of the molecule. A linear response was obtained in the different media for all the compounds with a detection limit of 1.96 × 10−6 M, 2.32 × 10−6 M, 1.44 × 10−6 M and 7.10 × 10−7 M for compounds 1, 2, 3 and 4 respectively.

Novel Indole-Based Analogs of Melatonin: Synthesis and in Vitro Antioxidant Activity Studies

The aim of this study was to synthesize and examine possible in vitro antioxidant effects of indole-based melatonin analogue compounds. As a part of our ongoing study nineteen indole hydrazide/hydrazone derivatives were synthesized, characterized and their in vitro antioxidant activity was investigated by three different assays: by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe, by examining their protective effect against H2O2-induced membrane lipid peroxidation and by determining their inhibitory effect on AAPH–induced hemolysis of human erythrocytes. The results indicated significant strong antioxidant activity for most of the compounds, when compared to melatonin.

Investigation of Antimicrobial Activities of Indole-3-Aldehyde Hydrazide/Hydrazone Derivatives

Background: Indoles and hydrazone-type compounds constitute an important class of compounds for new drug development in order to discover an effective compound against multi-drug-resistant microbial infections. Methods: A series of indole-3-aldehyde and 5-bromoindole-3-aldehyde hydrazide and hydrazones was evaluated for their in vitro antimicrobial activities using the 2-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Bacillus subtilis and Candida albicans. The minimum inhibitory concentration (MIC) was determined for test compounds and for the reference standards sultamicillin, ampicillin, fluconazole and ciprofloxacin. Results: Compounds possessed a broad spectrum of activity having MIC values of 6.25–100 mg/ml against the tested microorganisms. Compounds 1a–1j, in particular, displayed better activity against MSRA and significant activity against S. aureus relative to ampicillin. Unexpectedly, indole nicotinic acid hydrazides showed no significant activity while indole anisic acid hydrazides displayed better activity. Conclusion: The results may be instructive to researchers attempting to gain more understanding of the antimicrobial activity of indole hydrazide/hydrazone-type compounds.

Melatonin analogue new indole hydrazide/hydrazone derivatives with antioxidant behavior: Synthesis and structure–activity relationships

Melatonin (MLT) is a hormone produced in the brain by the pineal gland, from the amino acid tryptophan. It is also an antioxidant hormone with a particular role in the protection of nuclear and mitochondrial DNA. In recent years, many physiological properties of MLT have been described resulting in much attention in the development of synthetic compounds possessing the indole ring. Sixteen MLT analogue indole hydrazide/hydrazone derivatives were synthesized and in vitro antioxidant activity was investigated. Most of the compounds showed significantly higher activity than MLT at 10− 3 M and 10− 4 M concentrations.

Recent Developments of Melatonin Related Antioxidant Compounds

Melatonin is known for its radical scavenger activity, which is related to its ability to protect cells from different kinds of oxidative stress. Oxidative stress has been implicated in the development of neurodegenerative diseases like Parkinson, Alzheimers disease, Huntingtons disease, epileptic seizures, stroke, and as a contributor to aging and some cancer types. The antioxidant properties of melatonin include scavenging free radicals and the regulation of the activity and expression of antioxidant and pro-oxidant enzymes. Due to its free radical scavenger and antioxidant properties, multiple melatonin-related compounds such as melatonin metabolites and synthetic analogues are under investigation to determine which exhibit the highest activity with the lowest side effects. This review addresses recent studies with melatonin and related compounds.

Synthesis and Antimicrobial Activity of Some New 2-Phenyl-N-substituted Carboxamido-1H-benzimidazole Derivatives

Some 1H‐benzimidazole‐carboxamide derivatives were prepared and their antimicrobial activities against Staphyloccus aureus, Escherichia coli and Candida albicans evaluated. Compounds 18, 22, and 25 exhibited the best activity against Candida albicans.

Antioxidant Properties of Melatonin and its Potential Action in Diseases

In recent years, relationship between free radicals and oxidative stress with aging, cancer, atherosclerosis, neurodegenerative disorders, diabetes, and inflammatory diseases became increasingly clear. Confirming the role of oxidants in numerous pathological conditions such as cancer, the antioxidants developed as therapeutics have been proven ineffective. It is well established that melatonin (MLT) and its metabolites are able to function as endogenous free-radical scavengers and broadspectrum antioxidants. Numerous studies also proved the role of MLT and its derivatives in many physiological processes and therapeutic functions, such as the regulation of circadian rhythm and immune functions. The aim of this review is to arouse attention to MLT as a potentially valuable agent in the prevention and/or treatment of some diseases.