LETROZOLE- AN ANTI BREAST CANCER DRUG

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LETROZOLE- AN ANTI BREAST CANCER DRUG
LOC HUA CHEMISTRY 12B- SEMINAR 11
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AN OVERVIEW OF BREAST CANCER

• What is breast cancer?
• A single cell in a tissue undergoes
  transformation which converts a normal cell to a
  cancer cell.
• The cell evades destruction, it proliferates to
  form a tumor, a mass of abnormal cells within
  otherwise normal tissue.
• If the abnormal cell remain at the original site,
  the lump is called a begin tumor.
• A malignant tumor becomes invasive enough to
  impair the functions of one or more organs. At
  this point the tumor is cancer.

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AN OVERVIEW OF BREAST CANCER

• 2. What factors can cause breast cancer?
• Women over 40 have higher risks of breast cancer
• Native Americans, Hispanics, and Asians have
  lower rates of breast cancer than Caucasians and
  African Americans
• Genetic factor and family history
• Because growth of breast tissue is highly
  sensitive to estrogens, the more a women is
  exposed to estrogen over her lifetime, the higher
  the risk for breast cancer
• Pregnancy appears to increase the risk of breast
  cancer for up to 15 years following the first
  birth, particularly in older women

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AN OVERVIEW OF BREAST CANCER

• 3. Stages of Breast Cancer
• Stage 0 This means that paitient either have
  DCIS which is an early age of breast cancer or
  LCIS which is not a cancer but increase the
  chance to have breast cancer.
• Stage I cancer is less than 1 inch across. The
  cancer is only in the breast and has not spread
  out.
• Stage II cancer is about 1 to 2 inches or larger
  and has spread to the lymph nodes under arm
• Stage III cancer has spread to tissues near the
  breast (skin or chest wall, including the ribs
  and the muscles in the chest). cancer has spread
  to lymph nodes inside the chest wall along the
  breast bone.
• Stage IV This stage is defined by either of the
  following the cancer has spread to other organs
  of the body, most often the bones, lungs, liver,
  or brain. the tumor has spread locally to the
  skin and lymph nodes inside the neck, near the
  collarbone.
• Recurrent In this stage, the cancer has come
  back (recurred) after treatment. It may come back
  in the breast, in the soft tissues of the chest
  (the chest wall), or in another part of the body.

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AN OVERVIEW OF BREAST CANCER

• Statistics of Breast Cancer

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Structure and Synthesis Letrozole

• Pharmacology of Letrozole
• A type of drug called an aromatase inhibitor
  which work by limiting the ability of an enzyme
  called aromatase to create estrogen.
• Letrozole comes in pill form and is taken once a
  day. Its also called Femara.
• Letrozole is a drug for patients that have been
  taking Tamoxifen for five years.

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Structure and Synthesis Letrozole

• Synthesis Letrolzole

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Structure and Synthesis Letrozole

• structure

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Structure and Synthesis Letrozole

• FT -IR of Letrozole

Show the amine group
Show the nitriles group
Show the aromatic ring
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Structure and Synthesis Letrozole

• 1H NMR

13C NMR
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Structure and Synthesis Letrozole
Carbon Chemical Shift (ppm) Proton Chemical Shift (ppm) Atom Number and Notes
66.36 6.81 (singlet) 1 (alkyl methine)
113.29   1,1' (benzene rings)
117.82   19, 21 (benzene rings)
128.9 7.70, 7.72 (doublet) 3, 5, 3', 5' (benzene rings)
132.91 7.28, 7.30 (doublet) 2, 6, 2', 6' (benzene rings)
141.76   4, 4' (benzene rings)
143.68 8.09 (singlet) 5 (triazole ring)
153.05 8.07 (singlet) 3 (triazole ring)
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Comparison between Tamoxifen and Letrozole
Tamoxifen Letrozole
1. Long term working After 5 years the drug becomes ineffective Continue after 5 years treatment
2. Effect no effect on the production of estrogen A very powerful aromatase inhibitor, suppresses the production of estrogen
3. Physical effect Effect on women sexual function, memory loss, stroke hot flashes, sweating, edema, sore muscles and fatigue
4. Pregnancy affect on the fetus cause fetal harm when administered to pregnant women
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Reference

• http//www.cancer.gov/newscenter/pressreleases/let
  rozoleQandA
• http//www.drugs.com/pdr/Femara_Tablets.html
• http//www.usdoj.gov/dea/programs/forensicsci/micr
  ogram/journal071203/mj071203_pg6.html
• http//www.fda.gov/cder/foi/label/2003/20726se8008
  _Femara_lbl.pdfsearch'synthesis20letrozole
• http//www.sante.univnantes.fr/pharma/biocit/publi
  spdf/p34.pdf
• http//www.reutershealth.com/wellconnected/doc06.h
  tml