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Monaldi Archives For Chest Disease =... Sep 2021Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward... (Review)
Review
Ranolazine derives from piperazine and has been approved as a drug for the therapy of chronic stable angina. It acts by selectively inhibiting the late sodium inward current. Moreover, ranolazine has other metabolic features which makes it effective in other diseases as well as coronary artery ones. In this paper I make an updated review of all possible therapeutic roles of ranolazine: through cardiology and beyond.
Topics: Acetanilides; Heart; Humans; Piperazines; Ranolazine
PubMed: 34498453
DOI: 10.4081/monaldi.2021.1806 -
Anti-cancer Agents in Medicinal... 2023Carbonic Anhydrases (CAs) are a family of metalloenzymes that catalyze the reversible interconversion of CO and water to bicarbonate and proton. CA isoforms I, II, IX,...
BACKGROUND
Carbonic Anhydrases (CAs) are a family of metalloenzymes that catalyze the reversible interconversion of CO and water to bicarbonate and proton. CA isoforms I, II, IX, and XII are considered physiologically and pharmacologically relevant.
OBJECTIVE
The objective of this study is to synthesize potent and selective tumor-associated CA IX and XII inhibitors.
METHODS
A library of 17 coumarin derivatives clubbed with piperazine and benzyl moiety was designed, synthesized and evaluated for its inhibitory effects and selectivity profile towards physiologically and pharmacologically relevant CA isoforms I, II, IX, and XII.
RESULTS
All the derivatives were found to be active against the tumor-associated isoforms IX and XII. The most active compound against hCA (human Carbonic Anhydrase) IX was found to possess a K of 229 nM, while the one against hCA XII had a K of 294.2 nM. Additionally, two of the compounds were found to have exquisite selectivity towards the off-target hCA I and II isoforms. Moreover, they were found to be approximately 20-fold more selective towards hCA IX than XII. The selectivity of the compounds was further investigated molecular modeling techniques.
CONCLUSION
Coumarin-piperazine hybrids were identified as potent and selective CA IX and XII inhibitors. Molecular modeling techniques provided interesting cues pertaining to observed selectivity.
Topics: Humans; Carbonic Anhydrase IX; Molecular Structure; Structure-Activity Relationship; Carbonic Anhydrase Inhibitors; Isoenzymes; Neoplasms; Antigens, Neoplasm; Coumarins; Piperazines
PubMed: 36733240
DOI: 10.2174/1871520623666230202123535 -
Drug Research Feb 2021Piperazine, a nitrogen-containing heterocyclic has acquired an inimitable position in medicinal chemistry because of its versatile structure, which has fascinated... (Review)
Review
Piperazine, a nitrogen-containing heterocyclic has acquired an inimitable position in medicinal chemistry because of its versatile structure, which has fascinated researchers to design novel piperazine based molecules having various biological actions. The subsistence of various compounds possessing diverse pharmacological activities in the literature further confirms this fact. Currently available analgesics and anti-inflammatory drugs are associated with side effects that limit their use. Moreover, the literature reveals the incredible anti-inflammatory and analgesic potential of piperazine derivatives along with their method of synthesis, therefore; the present review has been designed to collate the development made in this area that will surely be advantageous in designing novel piperazine based candidates with enhanced efficacy and less toxicity. An extensive literature survey was carried by scrutinizing peer reviewed articles from worldwide scientific databases available on GOOGLE, SCOPUS, PUBMED, and only relevant studies published in English were considered.
Topics: Analgesics; Animals; Anti-Inflammatory Agents; Humans; Piperazine
PubMed: 33336346
DOI: 10.1055/a-1323-2813 -
Journal of Agricultural and Food... Sep 2022Piperazine and homopiperazine are well-studied heterocycles in drug design that have found gainful application as scaffolds and terminal elements and for enhancing the... (Review)
Review
Piperazine and homopiperazine are well-studied heterocycles in drug design that have found gainful application as scaffolds and terminal elements and for enhancing the aqueous solubility of a molecule. The optimization of drug candidates that incorporate these heterocycles in an effort to refine potency, selectivity, and developability properties has stimulated the design and evaluation of a wide range of bioisosteres that can offer advantage. In this review, we summarize the design and application of bioisosteres of piperazine and homopiperazine that have almost exclusively been in the drug design arena. While there are ∼100 approved drugs that incorporate a piperazine ring, only a single marketed agricultural product is built on this heterocycle. As part of the review, we discuss some of the potential reasons underlying the relatively low level of importance of this heterocycle to the design of agrochemicals and highlight the potential opportunities for their use in contemporary research programs.
Topics: Drug Design; Piperazine; Structure-Activity Relationship
PubMed: 35675050
DOI: 10.1021/acs.jafc.2c00726 -
ChemMedChem Jun 2021Depression is the single largest contributor to global disability with a huge economic and social burden on the world. There are a number of antidepressant drugs on the... (Review)
Review
Depression is the single largest contributor to global disability with a huge economic and social burden on the world. There are a number of antidepressant drugs on the market, but treatment-resistant depression and relapse of depression in a large number of patients have increased problems for clinicians. One peculiarity observed in most of the marketed antidepressants is the presence of a piperazine substructure. Although piperazine is also used in the optimization of other pharmacological agents, it is almost extensively used for the development of novel antidepressants. One common understanding is that this is due to its favorable CNS pharmacokinetic profile; however, in the case of antidepressants, piperazine plays a much bigger role and is involved in specific binding conformations of these agents. Therefore, in this review, a critical analysis of the significance of the piperazine moiety in the development of antidepressants has been performed. An overview of current developments in the designing and synthesis of piperazine-based antidepressants (2015 onwards) along with SAR studies is also provided. The various piperazine-based therapeutic agents in early- or late-phase human testing for depression are also discussed. The preclinical compounds discussed in this review will help researchers understand how piperazine actually influences the design and development of novel antidepressant compounds. The SAR studies discussed will provide crucial clues about the structural features and optimizations required to enhance the efficacy and potency of piperazine-based antidepressants.
Topics: Antidepressive Agents; Depression; Drug Development; Humans; Molecular Structure; Piperazine; Structure-Activity Relationship
PubMed: 33751807
DOI: 10.1002/cmdc.202100045 -
Environmental Science and Pollution... Dec 2021The present study has been carried out to evaluate the effects of piperazine and EDTA (ethylenediaminetetraacetic acid) in the garden snail, Cornu aspersum. EDTA and...
The present study has been carried out to evaluate the effects of piperazine and EDTA (ethylenediaminetetraacetic acid) in the garden snail, Cornu aspersum. EDTA and piperazine-like chemicals are widely used in various pharmaceutical, household, and industrial applications. The snails after collection were kept in different earthen pots and treated with these chemicals at different concentrations. A higher concentration of these chemicals led to a change in foot color from light to dark brown and loss in average weight with time. It has been found that a 10-fold increase in piperazine and EDTA concentration reduces weight by approximately 12.7- and 11.6-fold, respectively. Further, the study provides an insight into the altered antimicrobial activity of crude extract when treated with ligands. Additionally, the variations in the electrolytes in the mucus sample have been observed with the mean standard deviation (± SD) of 6.4 and 2.4 for Na and K ions, respectively.
Topics: Animals; Anti-Infective Agents; Edetic Acid; Electrolytes; Piperazine; Snails
PubMed: 34327636
DOI: 10.1007/s11356-021-15543-5 -
Future Medicinal Chemistry Apr 2023The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer...
The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer activities. Twenty-four scaffolds were synthesized a click-inspired synthetic protocol and were assayed for anticancer activity using the methyl thiazolyl tetrazolium assay and for antimicrobial potency by serial dilution. Among all the tested 1,2,3-triazole scaffolds, compounds (IC: 5.22 ± 0.05 μM) and (IC: 5.34 ± 0.13 μM) exhibited good anticancer activity, and also showed notable antimicrobial activity. Molecular docking studies of potent analogs and were performed to provide an insight into their binding interactions. Compound is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.
Topics: Molecular Docking Simulation; Triazoles; Piperazine; Anti-Infective Agents; Structure-Activity Relationship; Antineoplastic Agents; Molecular Structure
PubMed: 37170810
DOI: 10.4155/fmc-2022-0316 -
Journal of the American Academy of... Sep 2022In this issue, readers can review a multisite, double-blind, randomized, controlled trial (DBRCT) of vortioxetine for adolescent major depression (AMD) by Findling...
In this issue, readers can review a multisite, double-blind, randomized, controlled trial (DBRCT) of vortioxetine for adolescent major depression (AMD) by Findling et al. The investigators deserve credit for this industry-sponsored study's several innovations: initial treatment following current guidelines, efforts to reduce placebo response rates (PRRs), and creation of both placebo- and active-control arms. The Journal deserves our respect for its commitment to highlighting these innovations, despite the trial's negative result. It is essential to perform treatment studies in adolescents, and this study underscores the fallacy of presuming that drugs showing efficacy in adults will be as effective in our patients.
Topics: Adolescent; Adult; Humans; Depression; Depressive Disorder, Major; Double-Blind Method; Piperazines; Sulfides; Vortioxetine; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 35364250
DOI: 10.1016/j.jaac.2022.03.019 -
Acta Pharmaceutica (Zagreb, Croatia) Dec 2020Piperazine derivatives are a group of compounds with a psychostimulant effect. They are an alternative to illegal drugs. They are being searched for recreational use due... (Review)
Review
Piperazine derivatives are a group of compounds with a psychostimulant effect. They are an alternative to illegal drugs. They are being searched for recreational use due to their psychoactive and hallucinogenic effects. The high popularity of these compounds can be noticed all over the world due to easy purchase, lack of legal regulations and incorrect assessment of the safety of use. The recreational use of piperazine derivatives can often result in chronic and acute health problems and additionally with unpredictable remote effects. It is also common to take mixtures of psychoactive compounds. This hinders the correct diagnosis and treatment of patients with poisoning. The presented work is an illustration of the wide problem of piperazine derivatives abuse. The health effects and the possibility of identifying these compounds in preparations and biological material are described.
Topics: Animals; Designer Drugs; Humans; Illicit Drugs; Piperazines; Psychotropic Drugs; Substance-Related Disorders
PubMed: 32412428
DOI: 10.2478/acph-2020-0035 -
Environmental Entomology Jun 2023Recently, there are many studies suggesting antibacterial, antifungal, and anthelmintic agents as alternative chemicals to insecticides. In this study, the oxidative and...
Recently, there are many studies suggesting antibacterial, antifungal, and anthelmintic agents as alternative chemicals to insecticides. In this study, the oxidative and genotoxic effect of Piperazine, a clinically important hexahydropyrazine anthelmintic, on Galleria mellonella L. hemolymph tissue by adding artificial diet were investigated. Galleria mellonella larvae were reared until 7th larval stage in artificial diet containing 0.001, 0.01, 0.1, and 1 g piperazine per 100 g of diet. Using hemolymph collected from 7th-instar larvae, the amount of lipid peroxidation final product malondialdehyde (MDA), protein oxidation product protein carbonyl (PCO), and detoxification enzymes glutathione S-transferase (GST) and cytochrome P450 monooxygenase (cyt P450) activity, comet assay were measured. According to the results obtained, when the piperazine high concentrations tested with the control group were compared, statistically significant differences were found in MDA, PCO content, cyt P450, GST activity, and comet assay in the hemolymph of the insect. While MDA content was 0.01 ± 0.0021 nmol/mg protein in the control group, this amount increased approximately 2-fold at the highest concentration (0.0231 ± 0.0050 nmol/mg protein). On the other hand, when the control group and the highest piperazine concentration were compared in the GST and cyt P450 activity, it was determined that there was a statistically significant increase. We obtained similar results in comet assay and micronucleus formation data. This study showed that the tested piperazine concentrations caused significant changes in the detoxification capacity, oxidative stress, and genotoxic markers in the insect's hemolymph tissue.
Topics: Animals; Hemolymph; Piperazine; Moths; Larva; Oxidative Stress; DNA Damage
PubMed: 37043612
DOI: 10.1093/ee/nvad028