FORMED CELL STRUCTURE AS POTENTIAL TARGET FOR

CHEMOTHERAPY

Submited By :
Attiya amjad
Roll No(10McolE17)
Submited To:
Sir nawazish Hussain
INTRODUCTION
 The concept of drug targeting was first mentioned by Paul Ehrlich.
 He suggested the hypothetical “magic bullet”;
 first one should recognize and bind the target
 Second should provide a therapeutic action in this target.
 Currently, the concept of ‘magic bullet’ includes a coordinated
behavior of three components:
 Drug
 Targeting moiety
 Pharmaceutical carrier
DRUG TARGETING
 Drug targeting is defined as the ability of a drug molecule to accumulate in
the target organ or tissue selectively.
SIGNIFICANCE
 Drug targeting can overcome the non-specific toxic effect of
conventional drug delivery.
 This may also reduce the amount of drug required to dose.
FORMED CELL STRUCTURE AS POTENTIAL TARGET
1. The Membrane
 Similarity in the membrane composition of the bacteria and mammals.
 This structure can be easily disrupted in the bacteria and in some fungi than
in the mammals.
EXAMPLES
 Cationic Detergent Antibiotics
 Polyene Antibiotics
 Azoles
Cationic Detergent Antibiotics
 Polymyxin B is derived from the bacterium Bacillus polymyxa.
 Polymyxin B is an antibiotic primarily used for resistant Gram-
negative infections except the Proteus and Neisseria genera.

 Polymyxins are cationic, basic peptides that act like detergents (surfactants).
MECHANISM OF ACTION
 The molecules contained in polymyxins are positively charged, while the
lipopolysaccharides (LPS) present in the cell wall of Gram-negative
bacteria, are negatively charged.
 Polymyxins bind to the Gram-negative bacterial cell membrane
phospholipids, producing a disruptive physicochemical effect, which leads
to cell-membrane permeability changes and ultimately cell death.
 The initial association is through electrostatic interactions.
 Divalent ions Ca2+ n Mg2+
 Increase in the permeability of the cell envelope consisting of the cell wall
and the cytoplasmic membrane, leakage of cell contents, and subsequently
cell death.
 A secondary target site for polymyxins is the type II NADH-Quinone
oxydoreductase respiratory enzyme of the inner bacterial membrane. These
enzymes are an integral part of the bacterial electron transport pathway.
Newer studies show that polymyxins inhibit these enzymes in both Gram
positive and Gram negative bacteria.
 Third action of polymixins is Anti-Endotoxin effect.
Polyene Antibiotics
 Amphotericin B is a polyene macrolide antibiotic derived from the
actinomycete Streptomyces nodosus.
 Amphotericin B has a relatively broad spectrum of action and is useful in
treating cases of candidosis, histoplasmosis, blastomycosis, aspergillosis and
mucormycosis.
MECHANISM OF ACTION
 Polyenes bind to ergosterol. The consequence of this binding includes
disruption of the osmotic integrity of the membrane, with leakage of
intracellular potassium and magnesium, and also the disruption of oxidative
enzymes in target cells
 Researchers have found evidence that amphotericin B also causes oxidative
stress within the fungal cell, but it remains unclear to what extent this
oxidative damage contributes to the drug's effectiveness.
Azoles
 The mechanism of action of itraconazole is the same as the
other azole antifungals: it inhibits the fungal-mediated synthesis
of ergosterol, via inhibition of lanosterol 14α-demethylase.
 Itraconazole is pharmacologically distinct from other azole antifungal agents
in that it is the only inhibitor in this class that has been shown to inhibit both
the hedgehog signaling pathway and angiogenesis.

2. DNA
 BLEOMYCIN:
 Bleomycin is a glycopeptide antibiotic with a unique mechanism of
antitumor activity.
 The drug binds to guanosine-cytosine-rich portions of DNA.
MECHANISM OF ACTION
 Molecular oxygen, bound by the iron, can produce highly reactive free
radicals and Fe(III). The free radicals produce DNA single-strand breaks at
3'-4' bonds in deoxyribose.
 Cytotoxicity is cell-cycle-phase specific for G2 phase
3. Microtubules
 Albendazole
Albendazole causes degenerative alterations in the tegument and intestinal
cells of the worm by binding to the colchicine-sensitive site of tubulin, thus
inhibiting its polymerization or assembly into microtubules.
MECHANISM OF ACTION
 Impaired uptake of glucose.
 Depletion of the glycogen stores.
 Degenerative changes in the endoplasmic reticulum, the mitochondria of the
germinal layer, and the subsequent release of lysosomes result in decreased
production of adenosine triphosphate (ATP), which is the energy required
for the survival of the helminth.
 FORMED CELL STRUCTURE AS POTENTIAL TARGET
 Vincristine/Vinblastine
 Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for
various cancers including breast cancer, Hodgkin's disease, Kaposi's
sarcoma, and testicular cancer.
 The vinca alkaloids are considered to be cell cycle phase-specific.

MECHANISM OF ACTION
 The antitumor activity of Vincristine is thought to be due primarily to
inhibition of mitosis at metaphase through its interaction with tubulin.
 Vincristine may also interfere with:
1) Amino acid, cyclic AMP, and glutathione metabolism
2) calmodulin-dependent Ca2+-transport ATPase activity
3) Cellular respiration
4) Nucleic acid and lipid biosynthesis
 Vinblastine
Vinblastine inhibits angiogenesis. Angiogenesis is an essential step in a
tumor’s transition to malignancy.
Inhibition of mitosis at metaphase through its interaction with tubulin.
 Vinblastine binds to the microtubular proteins of the mitotic spindle, leading
to crystallization of the microtubule and mitotic arrest or cell death.

4. Food Vacuoles
 Chloroquine
 Quinoline-containing drugs such as chloroquine and quinine have had a long
and successful history in antimalarial chemotherapy.
 Prevent hemoglobin degradation.

5. Muscle Fibers
 Some anthelminthic drugs have a selective action on muscle cells in
helminths
 Piperazine
 Agonist on parasite specific chloride channels gated by GABA in nematode
muscles.
 Hyperpolarizes the muscle fibre membrane and paralysing the worm.
REFERENCES:
 http://www.americanpharmaceuticalreview.com/Featured-Articles/148744-
Key-Targeting-Approaches-for-Pharmaceutical-Drug-Delivery/
 http://www.antimicrobe.org/d05.asp
 https://www.ncbi.nlm.nih.gov/pubmed/11801575
 https://www.google.com.pk/search?q=bleomycin+mechanism+of+action&s
ource=lnms&tbm=isch&sa=X&ved=0ahUKEwjFjdn8qbLWAhVIP5oKHbi-
D6QQ_AUICigB&biw=1280&bih=617#imgrc=4y9juGqyQ6qojM:
 https://www.ncbi.nlm.nih.gov/pubmed/1384141
 https://www.drugbank.ca/drugs/DB00518
 https://www.drugbank.ca/drugs/DB00541
 https://www.drugbank.ca/drugs/DB00570
 https://www.ncbi.nlm.nih.gov/pubmed/8361993