1-1-diphenyl-2-picrylhydrazyl and indole

There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biphenyl Compounds; Carrageenan; Cattle; Cyclooxygenase 2; Dose-Response Relationship, Drug; Edema; Female; Humans; Indoles; Male; Molecular Structure; Oxadiazoles; Picrates; Pyrazoles; Rats; Rats, Wistar; Structure-Activity Relationship

Great effort has been devoted to design and synthesize biologically active and pharmacologically acceptable antioxidants. Although a number of efficient antioxidant compounds have been designed, synthesized, and tested in animals, none of them have demonstrated sufficient efficacy in human clinical trials without undesirable side effects. Thus new pharmacologically applicable antioxidants have been sought for. Substituted pyridoindoles represent a broad spectrum of pharmacologically active substances including highly effective scavengers of reactive oxygen species. The hexahydropyridoindole scaffold represents a valuable lead with a great deal of knowledge on molecular mechanisms of free radical scavenging, on bioavailability and toxicity. Its modification may yield congeners tailored according to specific requirements for antiradical efficacy, lipophilicity, and basicity, meeting the aim of providing a pharmacologically practicable antioxidant drug as exemplified by the novel derivative SMe1EC2.

Topics: Animals; Antioxidants; Biphenyl Compounds; Drug Design; Erythrocytes; Hemolysis; Humans; Indoles; Male; Picrates; Pyridines; Quantum Theory; Rats; Rats, Wistar; Time Factors

Increased levels of reactive oxygen species attributed to oxidative stress have been found to be responsible for the development of some vital diseases such as cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was observed that melatonin is a highly important antioxidant, and melatonin analogues are under investigation to find out improved antioxidant activity. In this study, 14 melatonin -based analogue indole amino acid and N-protected amino acid derivatives were synthesized and elucidated spectrometrically. To investigate the antioxidant activity of the synthesized compounds and to compare with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The results indicated that the synthesized new indole amino acid derivatives have similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assay but more potent activities in lipid peroxidation inhibition assay.

Topics: Amino Acids; Antioxidants; Biphenyl Compounds; Indoles; Lipid Peroxidation; Melatonin; Picrates