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 indolebased 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, structure and properties of some 5-R-4-phenyl-1,2,4-triazole-3-thiol derivatives

“…2-(4-(Indol-3-yl)propyl)-N-pheylhydrazine-1-carbothioamide (2.4). Yield 89%, m. p. 132-133 °C; 1 H NMR, δ (ppm): 1.09 (t, 3H, CH 3 ), 1.98 (q, 2H, CH 2 ), 2.36 (t, 2H, CH 2 ), 3.12 (m, 2H, CH 2 ), 3.42 (q, 2H, CH 2 ), 3.55 (s, 2H, Ar-CH 2 ) , 6 Molecular modeling was performed to evaluate in advance the prospects of further biological testing in vitro for the presence of antagonistic activity. A series of test compounds showed binding levels, at the average and below average, according to scoring functions.…”

“…Research in the field of indole compounds has been and remains relevant in the chemistry of heterocycles [1][2][3]. The reason for this interest is the participation of indole derivatives in the metabolic processes of living systems as biologically active compounds [6]. Derivatives of 1,2,4-triazole and pyrrole, which are structural fragments of a number of known drugs, are of no less interest [4,5].…”

A Smart and Efficient One‐Pot Green Synthesis of Novel 1, 2, 3‐Triazolyl Pyrazoline‐/Indazolyl‐Carbothioamide Hybrids under Solvent‐Free Grinding Strategy at Room Temperature

“…On the other hand, substituted pyrazoline derivatives attract great attention due to their wide range of medicinal and pharmaceutical activities . Interestingly, pyrazoline/indazolyl‐carbothioamide motifs possess numerous biological activities such as antitubercular, antimicrobial, tricyclic necroptosis inhibitors, antifungal, antianalgesic, antiamoebic, anti‐inflammatory, antidepressant and anticonvulsant etc. (Figure ).…”

Biologically important hydrazide-containing fused azaisocytosines as antioxidant agents

“…mitochondrial electron transport chain of cellular respiration) or from exogenous factors. It is well known that these species are capable of revealing both beneficial and harmful effects in the organism [1,2]. They fulfil essential functions in normal cell processes when are present in required quantities, while they can become toxic when are generated in excess [3].…”

“…They fulfil essential functions in normal cell processes when are present in required quantities, while they can become toxic when are generated in excess [3]. ROS are unstable and easily react with other molecules to achieve stability, so an overproduction of these species may lead to serious damages of all components of vital cells, including DNA, proteins and lipids [1][2][3]. These oxidative modifications can cause the disruption of normal cell physiology and ROS are believed to be associated with multiple disease conditions, such as carcinogenesis, inflammation, mutagenesis, genotoxicity and aging [4].…”