Erica Hilton investigada por contratar 2 maquiadores como assessores.
Erica Hilton investigada
Olhe para mim! Olhe esse cabelo, veja, está um bagaço, isso porque não tomei banho com shampoo de laranja.
Essa direita me persegue, essa direita fica falando mal de mim e dos meus assessores, isso é inadmissível, porém o amor vai vencer.
São fake news feitas contra mim, pessoa, eu não vou admitir que vocês façam isso.
Cabeleireiro, sim, maquiador, sim, mas eu vi algo mais. Nessas duas pessoas.
Algum tempo depois.
Depois de algumas horas percebemos o que realmente esses assessores conseguiram fazer, seu trabalho realmente é necessário para a deputada curtir e gastar o dinheiro público.
Eles são mágicos, olha o que eles fizeram comigo, agora posso ver a minha diva Beyoncé da melhor maneira possível.
Olha isso, olha essa pele maravilhosa, olha esse cabelo.
Para que gastar tempo com emendas?
Gastar tempo e dinheiro com estudos para os meus projetos de lei? Para saber se podem ou não afetar a economia, não!
O que eu quero é curtir e gastar o dinheiro público do jeito que eu quiser.
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An Overview of Anabolic Steroids (Anabolic–androgenic steroids)
Published for educational purposes – no endorsement or instruction is given regarding their use for sports, bodybuilding, or
other non‑medical purposes.
—
1. What Are Anabolic Steroids?
Definition: Synthetic derivatives of the male sex hormone testosterone that promote muscle growth (anabolism) and can also increase secondary sexual characteristics (androgenic effects).
Classification: They belong to a family called steroids—organic compounds with four interconnected rings, derived from cholesterol.
1.1 Chemical Structure
Feature Description
Core skeleton Four fused carbon rings (three six‑membered, one five‑membered).
Functional groups Hydroxyl (-OH), ketone (=O), and other substituents
at specific positions.
Steroid nomenclature Uses systematic names based on ring numbering (A–D) and functional group
locations.
1.2 Biosynthesis Pathway
Cholesterol → Pregnenolone
Pregnenolone → Progesterone
Progesterone → Testosterone → Estradiol
2. Key Pharmacological Properties
Property Relevance to Therapeutic Use
Potency Determines minimal effective dose; high potency reduces risk of off‑target effects.
Selectivity High receptor subtype selectivity limits side effects such as vasoconstriction or hormonal imbalance.
Metabolic Stability Influences duration of action and dosing frequency.
Toxicity Profile Acute toxicity, organ-specific damage (hepatic, renal).
Drug–Drug Interactions CYP450 inhibition/induction can alter plasma levels of concomitant medications.
—
4. Experimental Design for Comparative Evaluation
A. In‑Vitro Potency & Selectivity Assays
Radioligand Binding
– Use membranes from cells expressing α2A, α2B, and
α2C receptors.
– Determine IC50 values for each compound against each receptor subtype.
Functional G‑Protein Activation
– Measure inhibition of cAMP production in HEK293
cells stably expressing human α2A.
– Calculate EC50 and maximal efficacy (% of control).
Cross‑Receptor Profiling
– Test activity at off‑target receptors (e.g., 5‑HT2A, β‑adrenergic) to assess selectivity.
Expected Outcomes
Compound α₂A IC₅₀ (µM) EC₅₀ (nM) Max.
Efficacy (%)
4‑(p‑MeO‑Ph) – Cl ~0.02 5 95
4‑(p‑MeO‑Ph) – F ~0.05 15 90
A lower IC₅₀/EC₅₀ indicates higher affinity, while efficacy close to 100 % confirms full agonism.
—
Conclusion
SAR Findings
– The 4‑p‑methoxyphenyl substituent is crucial for activity; it provides the necessary lipophilic
and electronic environment that interacts with the receptor pocket.
– Fluorine improves potency compared to chlorine due to optimal size, electronegativity, and polarizability,
whereas bromine’s larger size reduces binding affinity.
Optimal Substituent
– 4‑p‑methoxy‑fluoro (compound 3) is the most potent analog, showing the lowest IC₅₀/EC₁₀ values.
Future Directions
– Further optimization could involve varying the halogen position or introducing additional electron-withdrawing/donating
groups at other ring positions to fine-tune receptor interaction and pharmacokinetics.
– Structural biology studies (e.g., crystallography, cryo-EM) of the receptor in complex with compound 3
would clarify binding mode and guide rational design.
—
Prepared by:
Your Name
Lead Medicinal Chemist
—
End of Memorandum
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