StudentShare
Contact Us
Sign In / Sign Up for FREE
Search
Go to advanced search...
Free

Leukotrienes A4 Hydrolase Inhibitors - Lab Report Example

Cite this document
Summary
This paper 'Leukotrienes A4 Hydrolase Inhibitors' tells us that E- Resveratrol is a naturally occurring, potent LTA4 hydrolase inhibitor of high medical importance.  Being based on the stilbene skeleton, resveratrol can exist as both cis-(Z) and trans-(E) isomers, being the transisomer the most commonly found in nature…
Download full paper File format: .doc, available for editing
GRAB THE BEST PAPER94.3% of users find it useful
Leukotrienes A4 Hydrolase Inhibitors
Read Text Preview

Extract of sample "Leukotrienes A4 Hydrolase Inhibitors"

One of the most efficient ways to achieve (E)-resveratrol is by employing the Heck reaction.

As it is seen in scheme 1, the starting 3,5-diacetoxy-styrene (1) was coupled with the para-monoderivative (2). Deacetylation of the formed stilbene derivative afforded the desired isomer of resveratrol.

The starting material (1) was prepared through the Wittig reaction followed by subsequent acetylation of the produced phenol as can be illustrated on the following diagram. 

While addressing the topic of trans-resveratrol, the research does not make any contribution in the area of cis-resveratrol synthesis and application. (Farina, Guiso, and Marra, 2002).

To fill that gap, it is worth mentioning other methods of resveratrol synthesis. For example, Roberti, et al. (2003) synthesized a series of cis- and trans-resveratrol (Scheme 3) derivatives using the following Wittig reaction. 

The groups marked as “R” are both silicon and carbon-containing ethers. The silicon-containing groups were further removed and the ability to induce apoptosis in cells of HL60 promyelocytic leukemia as well as cell growth inhibition properties of produced cis and trans-resveratrol derivatives were investigated. In most cases, trans isomers were less effective than their cis counterparts. It was also established that the following two products stand out for showing the best results in the mentioned tests.  

Comparing the accumulated results, the authors concluded that structural changes in the stilbene backbone will undeniably lead to the production of powerful apoptosis-reducing agents.

            The described research takes the concept of resveratrol-based drugs to a new level but does not mention the poor stability of cis-resveratrol (4). The information about cis-resveratrol is not as abundant as it is for trans isomers. 

Cis-resveratrol has shown antioxidant properties antiplatelet properties and affects cytoplasmic calcium levels in vascular smooth muscle cells Cis-resveratrol (4) has also been shown to inhibit kinase activity, a factor related to cancer (Jayatilake et al., 1993) and has a significant modulatory effect on the nuclear factor kappa B signaling pathway (Leiro et al, 2005) and, consequently, an important antioxidant role that may partially explain the cardioprotective effects attributed to long-term moderate red wine consumption. That was the main reason for our design of a cis-revere analogous (5) by modulative pharmacomodulation. (Scheme 5). 

Scheme 5: cis-resveratrol (4) autists analog( 5) produced by modulative pharmacomodulation.

            The compound preserves cis-resveratrol’s essential structural requirements and does not have the possibility of isomerization like it happens with natural cis-resveratrol (Trela and Waterhouse, 1996). For the synthesis of the resveratrol analog (5), we need to prepare the corresponding nitro derivative (6) from the respective aldehyde (7) using the methodology developed by Dauzone (1986) as described in scheme 6.

To prepare compound 5, we need to perform the Suzuki-Miyaura condensation (Beaumard et al., 2009) as described in scheme 7.

After treatment of the nitro derivative 9 with sodium aside in DMSO (Quiclet and Zard, 2005) and deprotection, we should be able to obtain the desired compound 5 (Scheme 8).

To assess cell growth inhibition properties MTT assay will be conducted. This colorimetric test is possible to apply in this particular case as LTA4H is an enzyme that reduces MTT. To do that 96-well plates will be populated with studied cancer cells(5000/well). To produce consistent results, six measurements should be done, repeating each concentration three times. At 370C MTT (5 mg/ml) for 4h will be added to the cells grown in various experimental conditions. As a consequence, purple formazan will be accumulated by the reduction of MTT in the mitochondria of the living cells. Formosan is stabilized by DMSO. The amount of reduced MTT provides information about the number of viable cells and, therefore, effete activeness of the drug and cell proliferation.   
The obtained formazan in its crystal state will be solubilized with DMSO and the absorbance measured at 570 nm using a Dynatech MR 5000 spectrometer. As this type of spectrometer is designed for 96-well plates it is possible to do all the measurements from 1.7 to 2.2 seconds depending on its input parameters. 

Abbreviationsions

 

Ac2O

Acetic anhydride

DMF

Dimethylformamide

DMSO

Dimethyl sulfoxide

MTT

((3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)

n-BuLi

n-butyllithium

PPh3

Triphenylphosphine

Py

Pyridine

THE

Tetrahydrofuran

Read More
Cite this document
  • APA
  • MLA
  • CHICAGO
(Design, synthesis and pharmacological tests of leukotrienes A4 Lab Report - 1, n.d.)
Design, synthesis and pharmacological tests of leukotrienes A4 Lab Report - 1. https://studentshare.org/medical-science/1759864-design-synthesis-and-pharmacological-tests-of-leukotrienes-a4-hydrolase-inhibitors-as-potential-targets-of-interest-in-cancer-treatment
(Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Lab Report - 1)
Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Lab Report - 1. https://studentshare.org/medical-science/1759864-design-synthesis-and-pharmacological-tests-of-leukotrienes-a4-hydrolase-inhibitors-as-potential-targets-of-interest-in-cancer-treatment.
“Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Lab Report - 1”. https://studentshare.org/medical-science/1759864-design-synthesis-and-pharmacological-tests-of-leukotrienes-a4-hydrolase-inhibitors-as-potential-targets-of-interest-in-cancer-treatment.
  • Cited: 0 times

CHECK THESE SAMPLES OF Leukotrienes A4 Hydrolase Inhibitors

Pharmaceutical Evaluation Report: The drug is Singulair

leukotrienes are chemicals that the human body releases.... Pharmacological studies have shown that the cysteinyl leukotrienes usually activate a minimum of two receptors (Monson, 2008).... The drug works by blocking or simply inhibiting leukotrienes from performing their functions.... leukotrienes are chemicals that are usually released during inflammatory and allergic reactions by the human body (Dubrin, 2011).... People with asthma usually release leukotrienes which result in inflammation and high levels of mucous production within the airways....
16 Pages (4000 words) Literature review

Morpholins anti-cancer drugs

The aim of the present research was to analyze the effect of introducing a variety of functional groups to morpolins, aiming at designing more selective/potent β-D-galactosidase inhibitors.... The target compounds were characterised using H1, C13NMR, IR and were studied as inhibitors of β-D-galactosidase extracted from Bovine kidney....
13 Pages (3250 words) Dissertation

The action of a competitive inhibitor to that of a non-competitive enzyme inhibitor

inhibitors are of two types reversible or irreversible.... Reversible inhibitors are those which bind to the enzyme and cause inhibition but do not change the chemical structure of the enzyme.... Irreversible inhibitors are those which bind to the enzyme and change the chemical structure of the enzyme thus making them unable to perform its function accurately.... Many drugs are enzyme inhibitors (Chatterjea et al 2007; Murray 2009)....
2 Pages (500 words) Essay

Leukotrienes A4 Hydrolase Inhibitors as Potential Targets of Interest in Cancer Treatment

The author of the paper "Leukotrienes A4 Hydrolase Inhibitors as Potential Targets of Interest in Cancer Treatment" will begin with the statement that (E)-Resveratrol is a naturally occurring, potent LTA4 hydrolase inhibitor of high medical importance.... ... ... ... Being based on the stilbene skeleton, resveratrol can exist as both cis-(Z) and trans-(E) isomers, being the trans isomer the most commonly found in nature (Romero-Perez et al, 1996)....
3 Pages (750 words) Literature review

Purification of Extracellular Cysteine Protease Inhibitor

This leads to the conclusion that the inhibitor is most effective on certain cysteine proteases, and prompts the comparison of ECPI-2's inhibitory spectrum to that of microbial originating inhibitors such as leupeptin and antipain; suggesting ECPI-2 as a unique cysteine protease inhibitor....
6 Pages (1500 words) Assignment

Adrenal Cortex and Adrenal Medulla in the Endocrine Response to Stress

Introduction: Each adrenal gland is, in effect, structurally and functionally two endocrine glands in one in that it is comprised of an outer cortex surrounding an inner medulla.... The cortex contains three histologically distinct zones from out to inward.... These are the zona glomerulosa, zona fasciculata, and zona reticularis....
6 Pages (1500 words) Essay

Inhibitory Effects of Fruit Juices on Cytochrome

On the other hand, Raspberry and Plum's juices are other non-competitive inhibitors.... This paper "Inhibitory Effects of Fruit Juices on Cytochrome" discusses fruit juices interactions with drugs.... A better understanding has been gotten on how the drugs are metabolized, how they transported inside the body and how different products might affect metabolism and interaction processes....
7 Pages (1750 words) Research Paper

Post Translational Modification and Glutathionylation

The paper "Post Translational Modification and Glutathionylation" tells that glutathionylation not only stabilizes the proteins but also makes them functionally active allowing it to play a major role in biochemical reactions such as detoxification and active defense against antioxidants.... ... ...
17 Pages (4250 words) Thesis
sponsored ads
We use cookies to create the best experience for you. Keep on browsing if you are OK with that, or find out how to manage cookies.
Contact Us