A new class of 5-HT1A receptor antagonists with procognitive and antidepressant properties

Aims: 5-HT1A receptor antagonists constitute a potential group of drugs in the treatment of CNS diseases. The aim of this study was to search for new procognitive and antidepressant drugs among amide derivatives of aminoalkanoic acids with 5-HT1A receptor antagonistic properties. Materials & methods: Thirty-three amides were designed and evaluated in silico for their drug-likeness. The synthesized compounds were tested in vitro for their 5-HT1A receptor affinity and functional profile. Moreover, their selectivity over 5-HT7, 5-HT2A and D2 receptors and ability to inhibit phosphodiesterases were evaluated. Results: A selected 5-HT1A receptor antagonist 20 ( Ki = 35 nM, Kb = 4.9 nM) showed procognitive and antidepressant activity in vivo. Conclusion: Novel 5-HT1A receptor antagonists were discovered and shown as potential psychotropic drugs.

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Synthesis and evaluation trypanosomicidal activity of new derivatives of megazol

Pharmaceutical and Biological Evaluations ◽

10.26510/2394-0859.pbe.2018.05 ◽

2018 ◽

Vol 5 (2) ◽

pp. 40

Author(s):

Helena B. Leites ◽

Flávia S. Damasceno ◽

Ariel M. Silber ◽

Ronaldo Z. Mendonça ◽

Cristina Northfleet de Albuquerque

Keyword(s):

Cell Proliferation ◽

Positive Control ◽

In Vitro Test ◽

Biological Part ◽

Amide Derivatives ◽

Vitro Test ◽

South Americans ◽

Derivatives Of

Objective: This work aims at the synthesis of megazol analogs with antitrypanosomicidal activity. Chagas’disease is caused by Trypanosoma cruzi and is a debilitating disease that has both acute and chronic forms. Many South Americans suffer from the chronic form of Chagas’disease, and there is no treatment currently available.Methods: In the chemical part, classical techniques of heterocyclic synthesis as well as usual methods of identification were used. In the biological part the cell proliferation test was used in vitro and the IC 50.Results: We synthesized a series of derivatives of 2-(1-methyl-5-nitro-2-imidazolyl)-5-substituted-1,3,4-thiadiazoles where 1-acetyl, 1-propyl and 1-nonyl were used as the substituent (4,6,7). Derivatives without nitro group were also synthesized (3,12) along with thiosemicarbazones (8,9,10) and a 5-(5-nitro-2-furanyl)-1,3,4-thiadiazol-2-amine (11). These compounds were evaluated using an in vitro test where were measured the cell proliferation. The derivatives that obtained the best results underwent further tests, in which their IC50 was calculated. The data revealed that two compounds (4,6) were effective against the parasite (IC50= 0.354 µM; IC50= 2.13 µM) and besides that, obtained the same results as the positive control, antimycim and rotenone. All proposed structures were obtained in satisfactory yields and purities.Conclusions: In conclusion, the in vitro trypanocidal activity makes these compounds promising leads in the development of an effective therapeutic agent. However, this study must be completed by additional tests with in vitro amastigote/macrophage models or in vivo mouse models. Analyzing the amide derivatives, compounds (4) and (6) were the ones that presented the best results.

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2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOME): A Harmful Hallucinogen Review

Journal of Analytical Toxicology ◽

10.1093/jat/bkaa022 ◽

2020 ◽

Author(s):

Katarzyna Kamińska ◽

Paweł Świt ◽

Kamilla Malek

Keyword(s):

Case Reports ◽

Chemical Properties ◽

Kidney Injury ◽

Behavioral Experiments ◽

New Class ◽

Chemical Structures ◽

Current State ◽

Derivatives Of

Abstract NBOMes are N-benzylmethoxy derivatives of the 2C family compounds with N-2-methoxybenzyl moiety substituted by the methoxy group at the 2- and 5-position and the halogen group at the 4-position of the phenyl ring. These substances are a new class of potent serotonin 5-HT2A receptor agonist hallucinogens with potential harmful effects. The substitution with halogen of the already psychoactive phenethylamine produces a derivative (2C-I) with increased hallucinogenic effects. This class of hallucinogens has chemical structures very similar to natural hallucinogenic alkaloid mescaline and these are sold mainly via internet as a ‘legal’ alternative to other hallucinogenic drug-lysergic acid diethylamide (LSD). 25I-NBOMe is the first synthesized and one of the most common compound from NBOMes. Knowledge of pharmacological properties of 25I-NBOMe is very limited so far. There are only a few in vivo and in vitro so far published studies. The behavioral experiments are mainly related with the hallucinogenic effect of 25I-NBOMe while the in vitro studies concerning mainly the affinity for 5-HT2A receptors. The 25I-NBOMe Critical Review 2016 reported 51 non-fatal intoxications and 21 deaths associated with 25I-NBOMe across Europe. Case reports describe various toxic effects of 25I-NBOMe usage including tachycardia, hypertension, hallucinations, rhabdomyolysis, acute kidney injury and death. The growing number of fatal and non-fatal intoxication cases indicates that 25I-NBOMe should be considered as a serious danger to public health. This review aims to present the current state of knowledge on pharmacological effects and chemical properties of 25I-NBOMe and to describe reported clinical cases and analytical methods available for identification of this agent in biological material.

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In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkn214 ◽

2008 ◽

Vol 62 (3) ◽

pp. 547-554 ◽

Cited By ~ 34

Author(s):

R. Villar ◽

E. Vicente ◽

B. Solano ◽

S. Perez-Silanes ◽

I. Aldana ◽

...

Keyword(s):

Amide Derivatives ◽

Derivatives Of

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In vitro antioxidant and in vivo antidepressant activity of green synthesized azomethine derivatives of cinnamaldehyde

Indian Journal of Pharmacology ◽

10.4103/ijp.ijp_293_16 ◽

2017 ◽

Vol 49 (3) ◽

pp. 229 ◽

Cited By ~ 1

Author(s):

Sridevi Chigurupati ◽

SohrabAkhtar Shaikh ◽

JahidulIslam Mohammad ◽

KesavanarayananKrishnan Selvarajan ◽

AppalaRaju Nemala ◽

...

Keyword(s):

Antidepressant Activity ◽

Derivatives Of

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Antifilarial Activity of Constituents of Calophyllum inophyllum and their Derivatives

Natural Product Communications ◽

10.1177/1934578x1300800630 ◽

2013 ◽

Vol 8 (6) ◽

pp. 1934578X1300800 ◽

Cited By ~ 2

Author(s):

Jankiprasad ◽

Gunaganti Naresh ◽

Jyoti Gupta ◽

Shailja M. Bhattacharya ◽

Siron M. Rajendran ◽

...

Keyword(s):

Meriones Unguiculatus ◽

Acid Mixture ◽

Calophyllum Inophyllum ◽

Amide Derivatives ◽

Diastereomeric Mixture ◽

Drug Discovery Program ◽

Antifilarial Activity ◽

Derivatives Of

Elephantiasis is a classic sign of late-stage lymphatic filariasis. Although the infection can be treated with drugs, the chronic conditions may not be curable by currently available antifilarial drugs. In continuation of our drug discovery program, we identified potent antifilarial activity in a calophyllic acid and isocalophllic acid mixture, which was isolated from the leaves of Calophyllum inophyllum. The mixture inhibited the motility of adult Brugia malayi worms and microfilariae stage parasites at a concentration of 15.6 μg/mL with an IC50 of 2.1 and 5.5 μg/mL, respectively, in in vitro studies. The diastereomeric mixture also exhibited moderate in vivo antifilarial activity in the jird ( Meriones unguiculatus) model. A few derivatives of calophyllic acid and isocalophyllic acid were prepared and one of the amide derivatives turned out to be the most promising compound against the adult (MIC: 3.9 and IC50: 0.32 μg/mL) and microfilariae stage (MIC:1.9 and IC50: 0.26 μg/mL) parasites with a high selectivity index. The amide derivative has superior activity than the parent natural product, as well as the standard antifilarial drug, ivermectin.

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Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

Current Medicinal Chemistry ◽

10.2174/0929867325666180508090640 ◽

2019 ◽

Vol 26 (30) ◽

pp. 5609-5624

Author(s):

Dijana Saftić ◽

Željka Ban ◽

Josipa Matić ◽

Lidija-Marija Tumirv ◽

Ivo Piantanida

Keyword(s):

Molecular Weight ◽

Small Molecules ◽

Biomedical Applications ◽

Protein Targets ◽

New Class ◽

Rna Targets ◽

Covalently Linked ◽

Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

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Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620999200730160952 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ya-Nan Li ◽

Ni Ning ◽

Lei Song ◽

Yun Geng ◽

Jun-Ting Fan ◽

...

Keyword(s):

Annexin V ◽

Mtt Method ◽

Anthriscus Sylvestris ◽

Anti Tumor Activity ◽

Derivatives Of ◽

Toxicity In Vitro ◽

Ht 29 ◽

Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

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Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties

Pharmacopsychiatry ◽

10.1055/a-1293-8585 ◽

2020 ◽

Vol 54 (01) ◽

pp. 37-46

Author(s):

Kristina Friedland ◽

Giacomo Silani ◽

Anita Schuwald ◽

Carola Stockburger ◽

Egon Koch ◽

...

Keyword(s):

Essential Oil ◽

Hippocampal Neurons ◽

Day Treatment ◽

Neuronal Cell ◽

Antidepressant Activity ◽

In Vivo Models ◽

Antidepressant Effects ◽

Primary Hippocampal Neurons

Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology—resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function—we investigated the neurotrophic properties of Silexan in neuronal cell lines and primary hippocampal neurons. Results The antidepressant activity of Silexan (30 mg/kg BW) in the FST was comparable to the tricyclic antidepressant imipramine (20 mg/kg BW) after 9-day treatment. Silexan triggered neurite outgrowth and synaptogenesis in 2 different neuronal cell models and led to a significant increase in synaptogenesis in primary hippocampal neurons. Silexan led to a significant phosphorylation of protein kinase A and subsequent CREB phosphorylation. Conclusion Taken together, Silexan demonstrates antidepressant-like effects in cellular as well as animal models for antidepressant activity. Therefore, our data provides preclinical evidence for the clinical antidepressant effects of Silexan in patients with mixed depression and anxiety.

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