Antitubercular polyhalogenated phenothiazines and phenoselenazine with reduced binding to CNS receptors

Nizi, Maria Giulia; Desantis, Jenny; Nakatani, Yoshio; Massari, Serena; Mazzarella, Maria Angela; Shetye, Gauri; Sabatini, Stefano; Barreca, Maria Letizia; Manfroni, Giuseppe; Felicetti, Tommaso; Rushton-Green, Rowena; Hards, Kiel; Latacz, Gniewomir; Satała, Grzegorz; Bojarski, Andrzej J.; Cecchetti, Violetta; Kolář, Michal H.; Handzlik, Jadwiga; Cook, Gregory M.; Franzblau, Scott G.; Tabarrini, Oriana

doi:10.1016/j.ejmech.2020.112420

Cited by 18 publications

(18 citation statements)

References 54 publications

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“…Compound 50a significantly eradicated cell viability at concentrations between 10 and 100 μM ( p < 0.0001). Nevertheless, these results are in accordance with the hepatotoxicity examination of thioridazine, an antipsychotic agent that is still in use (Figure , panel C) …”

Section: Resultssupporting

confidence: 85%

“…Nevertheless, these results are in accordance with the hepatotoxicity examination of thioridazine, an antipsychotic agent that is still in use ( Figure 8 , panel C). 54 …”

Section: Resultsmentioning

confidence: 99%

“…3-Hydroxypropanamide derivatives were obtained according to a previously reported synthetic route shown in Scheme 3. 25,47 2-Bromo-3-hydroxypropanoic acid (52) has been obtained from unprotected serine. Designed amides (53a−e) were formed after activation of acid 52 by n-propanephosphoric acid anhydride (T3P).…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, these results are in accordance with the hepatotoxicity examination of thioridazine, an antipsychotic agent that is still in use (Figure 8, panel C). 52 Subsequently, a similar study was performed with the HEK-293 cell line. Overall, compounds 2RS,4RS-39c and 56a showed stronger toxic effects than in the HepG2 assay, where a significant (****p < 0.0001) decrease in HEK-293 cell viability was observed at the concentration of 25 μM.…”

Section: Molecular Modelingmentioning

confidence: 99%

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Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity

Gryzło

Zaręba

Malawska

et al. 2021

ACS Chem. Neurosci.

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Neuropathic pain resistance to pharmacotherapy has encouraged researchers to develop effective therapies for its treatment. γ-Aminobutyric acid (GABA) transporters 1 and 4 (mGAT1 and mGAT4) have been increasingly recognized as promising drug targets for neuropathic pain (NP) associated with imbalances in inhibitory neurotransmission. In this context, we designed and synthesized new functionalized amino acids as inhibitors of GABA uptake and assessed their activities toward all four mouse GAT subtypes (mGAT1–4). According to the obtained results, compounds 2 RS ,4 RS - 39c (pIC 50 (mGAT4) = 5.36), 50a (pIC 50 (mGAT2) = 5.43), and 56a (with moderate subtype selectivity that favored mGAT4, pIC 50 (mGAT4) = 5.04) were of particular interest and were therefore evaluated for their cytotoxic and hepatotoxic effects. In a set of in vivo experiments, both compounds 50a and 56a showed antinociceptive properties in three rodent models of NP, namely, chemotherapy-induced neuropathic pain models (the oxaliplatin model and the paclitaxel model) and the diabetic neuropathic pain model induced by streptozotocin; however compound 56a demonstrated predominant activity. Since impaired motor coordination is also observed in neuropathic pain conditions, we have pointed out that none of the test compounds induced motor deficits in the rotarod test.

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Section: Resultssupporting

confidence: 85%

“…Nevertheless, these results are in accordance with the hepatotoxicity examination of thioridazine, an antipsychotic agent that is still in use ( Figure 8 , panel C). 54 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Molecular Modelingmentioning

confidence: 99%

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Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity

Gryzło

Zaręba

Malawska

et al. 2021

ACS Chem. Neurosci.

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“…In wide medical practice, phenothiazine derivatives are also successfully used as antihistamines [ 6 ]. In addition, their antibacterial, antitumor, and antituberculosis effects are known [ 7 , 8 , 9 , 10 , 11 , 12 ]. The synthesis of new phenothiazine derivatives is still ongoing.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Properties of New Phenothiazine Derivatives

et al. 2022

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Phenothiazine and its derivatives have a number of properties that contribute to their wider practical use in the production of biologically active substances, drugs, dyes, etc. Therefore, the synthesis and study of new compounds is of great relevance. The aim of this work was to investigate the antioxidant activity of a number of new phenothiazine derivatives. The patterns of electroreduction of oxygen and its radicals in the presence of phenothiazine derivatives in aqueous ethanol media were studied by voltammetry. The influence of various factors on antioxidant activity was considered by the methods of experiment planning. The optimal conditions for the manifestation of the antioxidant activity of phenothiazine derivatives have been found, which seems to be relevant since it opens up new possibilities for their further use as complex preparations with antioxidant activity, including in psychiatric practice.

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Synthesis of Two Isomers of pyrido/benzo[b][1,4]selenazines: A Selective Catalyst‐Dependent Formation of C−N and C‐Se Bonds

Santos,

Pezzini,

Cargnelutti

et al. 2023

Adv Synth Catal

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This work describes the selective synthesis of a series of pyrido/benzo‐fused 1,4‐selenazines, through the reaction of bis(3‐amino‐2‐pyridyl) or bis(2‐aminophenyl) diselenides with different β‐dicarbonyl compounds. When molecular I2 was used as catalyst, a series of (Z)‐1‐(1H‐pyrido[2,3‐b][1,4]selenazin‐2(3H)‐ylidene)propan‐2‐ones were obtained. On the other hand, in the absence of catalyst, 1‐(2‐methyl‐1H‐pyrido[2,3‐b][1,4]selenazin‐3‐yl)ethan‐1‐ones could be prepared selectively. The structure of the prepared compounds was elucidated by NMR and HRMS analysis and confirmed by single crystal X‐ray diffraction. The versatility of the protocol was demonstrated not only by the access to a variety of 1,4‐selenazine derivatives, but also by the structural diversity in the 1,3‐dicarbonyl precursors, incorporating multifunctionalities in the synthesized heterocycles.

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Antitubercular polyhalogenated phenothiazines and phenoselenazine with reduced binding to CNS receptors

Cited by 18 publications

References 54 publications

Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity

Novel Functionalized Amino Acids as Inhibitors of GABA Transporters with Analgesic Activity

Antioxidant Properties of New Phenothiazine Derivatives

Synthesis of Two Isomers of pyrido/benzo[b][1,4]selenazines: A Selective Catalyst‐Dependent Formation of C−N and C‐Se Bonds

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