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

Leukotrienes A4 Hydrolase Inhibitors as Potential Targets of Interest in Cancer Treatment - Literature review Example

Cite this document
Summary
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…
Download full paper File format: .doc, available for editing
GRAB THE BEST PAPER97.7% of users find it useful
Leukotrienes A4 Hydrolase Inhibitors as Potential Targets of Interest in Cancer Treatment
Read Text Preview

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

Many synthetic pathways were developed to synthesize this highly promising compound. (Farina, Guiso, and  Marra, 2002).

            One of the most efficient ways to achieve (E)-resveratrol is by employing the Heck reaction. The process is highly advantageous as it produces only the desired product in exceptional 99% yield:

Scheme 1: Synthesis of (E)-resveratrol using Heck reaction

            As it is seen in scheme 1, the starting 3,5-diacetoxy-styrene (1) was coupled with the para-iododerivative (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.

Scheme 2: Preparation of 3,5-diacetoxy-stirene (1)

            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.

Scheme 3: Synthesis of stilbene derivatives

            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.  

Scheme 4: Highly promising cis-Resveratrol derivatives

            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 affect 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-resveratrol analog (5) by modulative pharmacomodulation. (Scheme 5).

Scheme 5: cis-resveratrol (4) and its 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.

 

Scheme 6

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

 

Scheme 7

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

 

Scheme 8

MTT assay:

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. In order 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, the effectiveness 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.

 

 

 

 

 

 

 

 

 

 

Abbreviations

 

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

THF

Tetrahydrofuran

 

Read More
Cite this document
  • APA
  • MLA
  • CHICAGO
(“Design, synthesis and pharmacological tests of leukotrienes A4 Literature review”, n.d.)
Design, synthesis and pharmacological tests of leukotrienes A4 Literature review. Retrieved from https://studentshare.org/health-sciences-medicine/1435246-design-synthesis-and-pharmacological-tests-of
(Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Literature Review)
Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Literature Review. https://studentshare.org/health-sciences-medicine/1435246-design-synthesis-and-pharmacological-tests-of.
“Design, Synthesis and Pharmacological Tests of Leukotrienes A4 Literature Review”, n.d. https://studentshare.org/health-sciences-medicine/1435246-design-synthesis-and-pharmacological-tests-of.
  • Cited: 0 times

CHECK THESE SAMPLES OF Leukotrienes A4 Hydrolase Inhibitors as Potential Targets of Interest in Cancer Treatment

Tyrosine kinase inhibitors as targeted agents for the treatment of cancer

The improvement in the 5-year and 10-year survival rates could be due to either early detection or better treatment or both and based on the histopathological type of malignancy.... The improvement in the 5-year and 10-year survival rates could be due to either early detection or better treatment or both and based on the histopathological type of malignancy.... The treatment was based on the difference in cell proliferation in normal and cancer cells (Broekman, 2011)....
45 Pages (11250 words) Dissertation

Morpholins anti-cancer drugs

For this reason they are often take part in interactions with substrates or other cells, consequently carbohydrates are of paramount importance in cellular interactions and disease processes such as cancer, infections or inflammations.... The produced clusters are often the ideal targets for antitumor antibodies.... The activity of this enzyme is associated with a variety of diseases therefore the produced morpholine derivatives have potential medical applications....
13 Pages (3250 words) Dissertation

Cancer Therapy and Standard Modes of Treatment

(Folkman, 2001) means that since it is a vascular treatment and it does not have its own blood supply it can only maintain it's life if it is getting blood from the nearby vessels which will not give it enough capability to increase in size and gets metastasized.... The paper describes Sustained Angiogenesis is one of the six Hallmarks of cancer determined by Hanahan and Weinberg in 2000 proposed six characteristic capabilities by which normal cells become cancer cells....
20 Pages (5000 words) Research Paper

Enzyme Inhibitors in Breast Cancer Therapy

in cancer cells, excessive mitotic signals activate the intrinsic pathway, as a result of mutations within signaling pathways (Mashima et al 2005; Ripple et al 2005).... Third-line therapy uses the medicine if patients relapse after the second treatment, which followed an initial treatment.... The present discourse 'Enzyme Inhibitors in Breast cancer Therapy' addresses modern methods of treating breast cancer, in particular, such surgical techniques as prophylactic removal of ovaries and shutting down of ovaries in case of detection of estrogen-progesterone dependent tumor on early stage....
19 Pages (4750 words) Coursework

Leukotrienes A4 Hydrolase Inhibitors

(Farina, Guiso, and Marra, The paper "Design, Synthesis and Pharmacological Tests of leukotrienes a4 hydrolase inhibitors" is a worthy example of a lab report on medical science.... Scheme 7 After treatment of the nitro derivative 9 with sodium azide in DMSO (Quiclet and Zard, 2005) and deprotection, we should be able to obtain the desired compound 5 (Scheme 8).... Cis-resveratrol has shown antioxidant properties, antiplatelet properties and affect cytoplasmic calcium levels in vascular smooth muscle cells Cis-resveratrol (4) has also shown to inhibit kinase activity, a factor related to cancer (Jayatilake et al....
3 Pages (750 words) Lab Report

Treatment of Cancer and Its Progress: Solving Cancer Problems

treatment of cancer has experienced progress in quantum bounds.... A closer look at this review would hint that while in some fields there has been a paradigm shift in treatment, such as the employment of targeted therapy in the management of breast cancer and the use of monoclonal antibody, in other areas, novel treatments have developed in tough chronic cancers such as the Multiple Myeloma and Glioblastoma Multiforme, giving hope to patients on prolonged life....
9 Pages (2250 words) Research Paper

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

In vitro, glutathionylation is studied under conditions of stress but recent advances in proteomic studies have helped in the study of some targets for glutathionylation in a cell without the induction of external stress.... Glutathione has several targets in a cell in which most of it functions as a protector or as a signal transducer [13]....
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