HIF-1α as a Target Molecule in the Use of Triazino-Indole Derivative on the Acoustic Trauma Model

The effect of triazino-indole derivative (Trisan) on hypoxia-inducible factor (HIF) expression level in the organ of Corti, when administering it for therapeutic and preventive purposes, was investigated using an acoustic trauma model in experimental animals (female F1 hybrids of CBA and C57BL/6 lines). Cytoflavin was used as a comparator product. Study product Trisan (1% solution) was injected intravenously, intramuscularly and intraperitoneally, in the dose of 5, 7 and 10 mg/kg 2 h after the acoustic trauma for therapeutic purposes and in the dose of 5, 7 and 10 mg/kg for 3 days before the acoustic trauma for preventive purposes. IHC methods were used to investigate the organ of Corti. Trisan was observed to increase HIF expression in hair cells and neurons of the spiral ganglion in case of acoustic trauma. Depending on the dose, the increased HIF-1 expression in hair cells and spiral ganglion occurred both after therapeutic and preventive use of Trisan. Maximum HIF expression in hair cells and ganglion was noted at the therapeutic and preventive drug dose of 10 mg/kg. Following experimental results, we conclude that the otoprotective effect of triazino-indole derivative is realized via its effect on HIF metabolism, which makes it a target molecule for the drug.

Search for Non-Protein Protease Inhibitors Constituted with an Indole and Acetylene Core

A possible inhibitor of proteases, which contains an indole core and an aromatic polar acetylene, was designed and synthesized. This indole derivative has a molecular architecture kindred to biologically relevant species and was obtained through five synthetic steps with an overall yield of 37% from the 2,2′-(phenylazanediyl)di(ethan-1-ol). The indole derivative was evaluated through docking assays using the main protease (SARS-CoV-2-Mpro) as a molecular target, which plays a key role in the replication process of this virus. Additionally, the indole derivative was evaluated as an inhibitor of the enzyme kallikrein 5 (KLK5), which is a serine protease that can be considered as an anticancer drug target.

A Review an Isatin, Isatin Derivatives and their Pharmacological Activity

Isatin or 1H-indole-2, 3-dione is an indole derivative. Isatin is an important class of heterocyclic compounds. Recently, heterocyclic compounds analogues and their derivatives have attracted strong interest in medicinal chemistry due to their biological and pharmacological properties. The structure have offered a high value of diversity that is proven useful for the development of new medicinal drugs and improved potency,less toxicity and good pharmacological activity. Isatin has a wide varity of pharmacological activities such as an antimicrobial, anticancer, antiviral, anticonvulsant, anti-inflammatory and analgesic etc. The aim of this review is to provide the recent efforts of scinentists in pharmacological screening of isatin, importants and synthesis of isatin derivatives,pharmacological action of isatin and their biological activity.

Effect of Bromination on the Quorum Sensing-Inhibiting Properties of Indole-3-Carboxaldehydes in Chromobacterium violaceum AHL System

Quorum sensing (QS) is a form of bacterial communication involved in the production of virulence factors in many species. As a result, inhibition of quorum sensing may be of use in mitigating pathogenesis. The signaling molecule indole is currently being investigated as a target for quorum sensing inhibition (QSI) and the indole derivative indole-3-carboxaldehyde (ICA) has been shown to inhibit quorum sensing-mediated behaviors in Escherichia coli. In this study, we investigate bromination as a method of increasing the QSI capabilities of indole carboxaldehydes. The IC50 values of three monobrominated indole carboxaldehydes (5-bromoindole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and 7-bromoindole-3-carboxaldehyde) were determined and compared to the IC50 value of ICA. The bromination of these indole carboxaldehydes reduced the IC50 values between 2- and 13-fold, indicating that bromination significantly increases the potency of these indole carboxaldehydes.

Aryl Hydrocarbon Receptors in Indole Derivative Treated Mice: Neuropharmacological Perspectives

Aim/objective. When applied in pharmacological doses, the indole derivative melatonin exhibits neuroactive and neuroprotective effects. Indoles and their metabolites, such as kynurenine, are ligands of aryl hydrocarbon receptors (AhR). This study aimed to evaluate the antiepileptic and analgesic activity of melatonin and two synthetic melatonin derivatives. The possible involvement of AhR and kynurenine in their neuropharmacological effects were also tested. Methods. The tested substances were: melatonin, two melatonin derivatives bearing aryl hydrocarbon moiety with either furyl or thienyl substitute (3e and 3f), and alpha naphthoflavone (ANF), an antagonist of AhR. After intraperitoneal injection of 30, 100, or 300 mg/kg of the tested agents for seven days, male mice ICR (25-30 g) were subjected to a corneal kindling seizure model. Two tests for analgesia, i.e., the hot plate test and the formalin test, were also applied. AhR and kynurenine concentrations were evaluated in brain homogenates. Results. Substances 3e and 3f demonstrated an antiepileptic activity comparable to that of melatonin. Some analgesic activity was also shown, albeit lower than that of melatonin in equivalent doses. For melatonin and 3f treated mice, dose-dependent increases in AhR and kynurenine levels in brain homogenates were recorded. The antagonist ANF neither blocks the antiseizure activity of the tested indoles, nor demonstrated analgesic activity. Conclusion. Melatonin and the two tested melatonin-aroylhydrazone derivatives bearing either furyl or thienyl substitute exhibit antiepileptic and analgesic activity. Our results did not support the involvement of AhR in the demonstrated neurobiological activity. Further studies are needed to elucidate their exact molecular mechanisms.

Preparation of novel imidazo[1,2-a]indole fluorophore and its application for detecting extreme pH of fungus

A novel pH fluorescent probe imidazo[1,2-a]indole derivative is reported. The probe is highly selective to strong acidic pH (pKa = 3.56) with high sensitivity and a fast response time (within 30 s). It is hardly interfered by ordinary metal ions and has good reversibility under strong acid conditions. The probe transfers charge under different pH conditions, and the response mechanism depends on the change of ICT. It can also be used for imaging in strong acidic Saccharomyces cerevisiae and detection of intracellular H+ as well.

Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage

Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.