Hanif Shirinzadeh

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.

Electrochemical Behavior of Indole-3-Carboxaldehyde Izonicotinoyl Hydrazones: Discussion on Possible Biological Behavior

Electrochemical techniques provide valuable information about drug molecules and their mechanisms in the body such as metabolism is getting one of the important actions in drug discovery. Since many physiological processes are depending on oxido-reduction reactions, it is not difficult to find associations between electrochemical and biological reactions regarding electron transfers. To investigate this proposal two compounds namely 1-methylindole-3-carboxaldehyde izonicotinoyl hydrazone and 5-chloro-1H-indole-3-carboxaldehyde izonicotinoyl hydrazone were synthesized, characterized and examined electrochemically using different voltammetric techniques in order to evaluate the possible biological behavior. The characteristics of the corresponding electrode reaction were discussed. A linear response was obtained in the different media for the compounds with low detection limits of the synthesized compounds.

Novel indole-based melatonin analogues substituted with triazole, thiadiazole and carbothioamides: studies on their antioxidant, chemopreventive and cytotoxic activities

Abstract Melatonin (MLT) is a well-known free-radical scavenger, involving in the prevention of cellular damage that can lead to cancer, ageing and a variety of neurodegenerative diseases. Research on MLT-related compounds has been required to optimise the maximum pharmaceutical activity with the lowest side effects. In our ongoing research, we have synthesized new indole-based MLT analogues as potential antioxidant agents by modifying the MLT molecule. In this study, we build on previous findings, through the synthesis, characterization and in vitro antioxidant profiling of a series of new indole-based MLT analogues which possess triazole, thiadiazole and carbothioamides on the third position on the indole ring. In vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe and their radical scavenging activity was assessed via the DPPH assay. In addition, in vitro cytotoxic effects of newly synthesized compounds were investigated in CHO-K1 cells using the MTT assay.

Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde hydrazone derivatives: bioisosteric melatonin analogues

Abstract Overproduction of reactive oxygen species results in oxidative stress that can cause fatal damage to vital cell structures. It is known that the use of antioxidants could be beneficial in the prevention or delay of numerous diseases associated with oxidative stress. Melatonin (MLT) is known as a powerful free-radical scavenger and antioxidant. It was found that indole ring of MLT can be employed by bioisosteric replacement by other aromatic rings. Quinoline derivatives constitute an important class of compounds for new drug development. Owing to quinoline and hydrazones appealing physiological properties and are mostly found in numerous biologically active compounds a series of quinoline-2-carbaldehyde hydrazone derivatives were synthesized as bioisosteric analogues of MLT, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox-sensitive fluorescent probe. Cytotoxicity potential of all compounds was investigated both by lactate dehydrogenase leakage assay and by MTT assay.

Synthesis and antioxidant activity evaluations of melatonin based analogue indole-hydrazide/hydrazone derivatives

Harmful effects of free radicals to the human body have been studied over the last decade. Overproduction of the free radicals can be responsible for tissue injuries that cause many health problems which include cancer, aging, heart diseases, neurological disorders, Alzheimers disease, Huntington disease and so on. Melatonin (MLT), the main secretory product of the pineal gland is a well-known antioxidant and free radical scavenger. It is a neurohormone produced from the amino acid tryptophan. In our earlier studies, new MLT-based analogues with changes in the 5-methoxy and 2-acylaminoethyl groups of MLT were synthesized and tested for their in vitro antioxidant potency in the DPPH, superoxide dismutase and lipid peroxidation (LP) assays.

Antimicrobial evaluation of indole-containing hydrazone derivatives.

There has been an increasing importance of drug-resistant pathogens in clinical microbiological and antibacterial research. Indoles and hydrazone-type compounds constitute important classes of compounds in the search for effective agents against multidrug-resistant microbial infections. In this study a series of 1-methylindole-3-carboxaldehyde hydrazone derivatives were evaluated for their in vitro antimicrobial activities using the two-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus, methicillinresistant S. aureus isolate, Escherichia coli, Bacillus subtilis, and Candida albicans. The minimum inhibitory concentration (MIC) of the test compounds and the reference standards sultamicillin, ampicillin, fluconazole, and ciprofloxacin was determined. All compounds possessed a broad spectrum of activity having MIC values of 6.25 - 100 μg/ml against the tested microorganisms. Aromaticity and disubstitution of the phenyl ring with especially fluorine and chlorine atoms were found to be significant for the antimicrobial activity

Antimicrobial Activities of New Indole Derivatives Containing 1,2,4-Triazole, 1,3,4-Thiadiazole and Carbothioamide

Objectives: In new antimicrobial drug development studies, indole and its derivatives create an important class of compounds. In addition, azoles and their derivatives were recognized to be associated with a variety of biologic activities such as antibacterial and antifungal. In this study antimicrobial activities of some indole derivatives mainly substituted with 1,2,4-triazole, 1,3,4-thiadiazole and hydrazinecarbothioamide were investigated to evaluate their efficacy. Materials and Methods: The efficacy of new compounds was evaluated using 2-fold serial dilutions against Staphylococcus aureus, MRSA, Escherichia coli, Bacillus subtilis, Candida albicans, and Candida krusei. Results: The MIC was determined for test compounds and for the reference standards sultamicillin, ampicillin, fluconazole, and ciprofloxacin. Conclusion: The compounds possessed a broad spectrum of activity having MIC values of 3.125-50 µg/mL against the tested microorganisms. This study provides valuable evidence that the indole-triazole derivative compound 3d holds significant promise as a novel antibacterial and antifungal lead compound.

Antimicrobial activity of indole-based melatonin analogues.

Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) have accomplished important rates of colonization and infection in most intensive care units. These multidrug-resistant strains of MRSA and VRE have been causing serious problems in health care. The rising clinical importance of drug-resistant pathogens has lent necessity to drug development research. In recent years, many 1H-indole derivatives including also Schiff base structures have been reported to exhibit chemotherapeutic properties such as antiviral, anti-tuberculosis, antifungal, and antibacterial activity. Hydrazone-type compounds containing an azomethine also represent a significant class of compounds for new drug development. The hydrazone group in molecules has an essential role in antimicrobial activity. It has been claimed that a number of hydrazide-hydrazone derivatives possess interesting antibacterial-antifungal and antituberculosis activities.