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Phenothiazines and Benzothiazines Synthesis and Activities
Research Guide
What is Phenothiazines and Benzothiazines Synthesis and Activities?
Phenothiazines and benzothiazines synthesis and activities refer to the chemical synthesis methods and biological properties of phenothiazine and benzothiazine compounds, including their antimicrobial, anticancer, neuroprotective, and antioxidant effects as explored in molecular biology research.
The field encompasses 33,705 works focused on synthesis techniques such as the Smiles rearrangement and biological activities like DNA synthesis inhibition. Phenothiazines appear in pharmaceuticals as nitrogen heterocycles, with 59% of unique small-molecule U.S. FDA approved drugs containing such structures (Vitaku et al., 2014). Sulfur-containing scaffolds, including those in phenothiazines, are prevalent in drugs for medicinal chemistry applications (Feng et al., 2016).
Topic Hierarchy
Research Sub-Topics
Phenothiazine Antimicrobial Activity
This sub-topic covers the mechanisms by which phenothiazines inhibit bacterial efflux pumps, disrupt biofilms, and combat multidrug-resistant pathogens. Researchers evaluate MICs, synergy with antibiotics, and clinical repurposing potential.
Phenothiazine Anticancer Mechanisms
Research examines phenothiazines' induction of apoptosis, autophagy, and ROS-mediated cytotoxicity in cancer cells. Studies include structure-activity relationships, tumor cell line screening, and in vivo efficacy.
Smiles Rearrangement Phenothiazine Synthesis
This area develops synthetic methodologies using Smiles rearrangement for efficient construction of phenothiazine scaffolds. Researchers optimize conditions, explore variants, and apply to diversity-oriented synthesis.
Phenothiazine Neuroprotective Effects
Studies investigate phenothiazines' protection against ischemia, neurodegeneration, and dopamine toxicity via antioxidant and anti-inflammatory actions. This includes animal models and receptor pharmacology.
Phenothiazine DNA Synthesis Inhibition
Researchers elucidate phenothiazines' intercalation, topoisomerase inhibition, and blockade of DNA replication in proliferating cells. Assays include comet assays, flow cytometry, and molecular docking.
Why It Matters
Phenothiazines and benzothiazines demonstrate antimicrobial activity against Mycobacterium tuberculosis, as measured by microplate Alamar blue assays compared to BACTEC 460 systems (Collins and Franzblau, 1997). Their sulfur scaffolds contribute to pharmaceuticals targeting infections and cancers (Feng et al., 2016). Neuroprotective properties are evident in analogs like NBQX, which inhibit non-NMDA glutamate receptors to protect against cerebral ischemia (Sheardown et al., 1990). These compounds address antibiotic-resistant infections through non-antibiotic mechanisms and inhibit DNA synthesis in carcinogenic contexts (Magee and Barnes, 1967).
Reading Guide
Where to Start
"Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals" by Vitaku et al. (2014), as it provides foundational data on nitrogen heterocycles like phenothiazines in 59% of FDA drugs, offering context for synthesis and activity relevance.
Key Papers Explained
Vitaku et al. (2014) establish nitrogen heterocycles' prevalence in 59% of FDA drugs, linking to phenothiazine importance; Feng et al. (2016) build on this by detailing sulfur scaffolds' synthesis in such drugs; Collins and Franzblau (1997) apply this to antimicrobial screening of phenothiazine-like compounds against tuberculosis; Sheardown et al. (1990) extend to neuroprotective glutamate inhibition with related quinoxalinediones.
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Research continues on phenothiazines for DNA synthesis inhibition and non-antibiotic management of resistant infections, with connections to enzyme inhibition and cancer signaling pathways like Wnt/β-catenin, though no recent preprints are available.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Analysis of the Structural Diversity, Substitution Patterns, a... | 2014 | Journal of Medicinal C... | 5.9K | ✕ |
| 2 | Dithiothreitol, a New Protective Reagent for SH Groups<sup>*</... | 1964 | Biochemistry | 2.0K | ✕ |
| 3 | Sulfur Containing Scaffolds in Drugs: Synthesis and Applicatio... | 2016 | Current Topics in Medi... | 1.9K | ✕ |
| 4 | Quinoline, quinazoline and acridonealkaloids | 2007 | Natural Product Reports | 1.7K | ✕ |
| 5 | Microplate alamar blue assay versus BACTEC 460 system for high... | 1997 | Antimicrobial Agents a... | 1.6K | ✓ |
| 6 | Carbonic anhydrase inhibitors | 2002 | Medicinal Research Rev... | 1.4K | ✕ |
| 7 | 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: a Neuro... | 1990 | Science | 1.1K | ✕ |
| 8 | Carcinogenic Nitroso Compounds | 1967 | Advances in cancer res... | 1.1K | ✕ |
| 9 | [3H]Ketanserin (R 41 468), a selective 3H-ligand for serotonin... | 1982 | Molecular Pharmacology | 1.1K | ✕ |
| 10 | Receptor activity and turnover of dopamine and noradrenaline a... | 1970 | European Journal of Ph... | 1.0K | ✕ |
Frequently Asked Questions
What role do phenothiazines play in FDA-approved pharmaceuticals?
Analysis of U.S. FDA approved drugs shows that 59% of unique small-molecule drugs contain a nitrogen heterocycle, with phenothiazines among the most common (Vitaku et al., 2014). These structures are key components in medicinal chemistry. Substitution patterns highlight their frequency in approved therapeutics.
How are sulfur scaffolds like those in phenothiazines synthesized for drugs?
Sulfur-containing scaffolds in phenothiazines and benzothiazines are synthesized for applications in antimicrobial and anticancer drugs (Feng et al., 2016). Methods include adaptations of the Smiles rearrangement. These scaffolds maintain prominence in pharmaceutical development.
What antimicrobial screening methods test phenothiazine activities?
Microplate Alamar blue assays screen phenothiazines against Mycobacterium tuberculosis and M. avium, offering high-throughput alternatives to BACTEC 460 (Collins and Franzblau, 1997). MICs of 30 agents were evaluated. This enables rapid compound testing.
How do phenothiazine-related compounds provide neuroprotection?
NBQX, a quinoxalinedione analog related to phenothiazine scaffolds, selectively inhibits quisqualate subtype glutamate receptors for cerebral ischemia protection (Sheardown et al., 1990). It shows no activity at NMDA sites. This supports neuroprotective applications.
What is the prevalence of works on phenothiazine synthesis and activities?
The topic includes 33,705 works covering synthesis and activities like antimicrobial and anticancer properties. Growth data over 5 years is not available. Keywords include Smiles rearrangement and DNA synthesis inhibition.
Open Research Questions
- ? How can Smiles rearrangement be optimized for scalable synthesis of benzothiazine derivatives with enhanced antimicrobial selectivity?
- ? What structural modifications to phenothiazines improve inhibition of DNA synthesis in antibiotic-resistant bacteria?
- ? Which neuroprotective mechanisms of phenothiazine analogs target glutamate receptors without NMDA interference?
- ? How do sulfur substitution patterns in phenothiazines influence their anticancer activity against renal and related cancers?
- ? What roles do phenothiazines play in modulating Wnt/β-catenin signaling for cancer therapy?
Recent Trends
The field maintains 33,705 works with no specified 5-year growth rate.
Core papers from 2016 (Feng et al.) emphasize sulfur scaffolds in phenothiazines for medicinal applications, while earlier works like Collins and Franzblau validate screening methods.
1997No recent preprints or news coverage indicate steady focus on synthesis via Smiles rearrangement and activities against tuberculosis.
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