the lord hath created medicines out of the earth and he that is wise will not abhor them n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
The Lord hath created medicines out of the earth and he that is wise will not abhor them PowerPoint Presentation
Download Presentation
The Lord hath created medicines out of the earth and he that is wise will not abhor them

Loading in 2 Seconds...

play fullscreen
1 / 29

The Lord hath created medicines out of the earth and he that is wise will not abhor them - PowerPoint PPT Presentation


  • 265 Views
  • Uploaded on

The Lord hath created medicines out of the earth and he that is wise will not abhor them. ECCLESIASTICUS, XXX VIII Quoted by Selman A. Waksman in his Nobel Lecture, 1952. The Waksman Lab. Actinomycin D – 1940 – Waksman and Woodruff Streptomyces antibioticus – chromo oligopeptide

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'The Lord hath created medicines out of the earth and he that is wise will not abhor them' - Lucy


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
the lord hath created medicines out of the earth and he that is wise will not abhor them

The Lord hath created medicines out of the earth and he that is wise will not abhor them

ECCLESIASTICUS, XXX VIII

Quoted by Selman A. Waksman

in his Nobel Lecture, 1952

the waksman lab
The Waksman Lab
  • Actinomycin D – 1940 – Waksman and Woodruff
    • Streptomyces antibioticus – chromo oligopeptide
    • Used for Wilm’s Tumor in children and a basic tool in development of molecular biology as inhibitor of RNA polymerase
  • Streptomycin – 1945- Waksman and Schatz
    • Streptomyces griseus – aminoglycoside
    • First antibiotic against TB. Also vs. bacterial meningitis
  • Neomycin – 1948 – Waksman and Lechevalier
    • Streptomyces fradiae – aminoglycoside - topical antibiotic
  • Candicidin – 1953 – Waksman and Lechevalier
    • Streptomyces griseus – polyene antifungal
  • Another 25 antibiotics
  • Waksman et al’s discoveries stimulated drug discovery work internationally from 1948 until today
use of secondary metabolites
Use of Secondary Metabolites
  • Helped double lifespan in 20th century
  • Reduced pain and suffering
  • Revolutionized medicine by facilitating organ transplantation

(Verdine, 1996)

facts about secondary metabolites
Facts About Secondary Metabolites
  • 10,000 microbial secondary metabolites have been discovered.
  • Actinomycetes produce about 75% of all described antibiotics.
  • Streptomyces species make 75% of all actinomycete secondary metabolites.
  • Streptomyces hygroscopicus strains produce over 180 different secondary metabolites.

(Omura, 1992; Zedan, 1993; Miyadoh, 1993)

anti infective market
ANTI-INFECTIVE MARKET

1996:

  • 160 ANTIBIOTICS
  • $23 BILLION MARKET

2000:

  • $55 BILLION MARKET
blockbuster markets for natural product derivatives
BLOCKBUSTER MARKETS FOR NATURAL PRODUCT DERIVATIVES

(Elander, 2002; Thayer, 2003; Strohl, 2004)

clavulanic acid
Clavulanic Acid
  • β-Lactamase inhibitor
  • Market is over $1 billion
  • Used in combination with susceptible penicillins.
    • With amoxycillin=Augmentintm
    • With ticarcillin=Timentintm

(Jensen and Paradkar, 1999)

carbapenems
CARBAPENEMS
  • Thienamycin discovered in 1970’s.
  • 40 naturally occurring forms, most from Streptomyces.
  • Broad spectrum antibiotics.
  • Resistant to most β-lactamases.

(Derzelle et al., 2002)

glycopeptides
GLYCOPEPTIDES
  • Sales of vancomycin and teicoplanin are $1 billion/year

(Williams and Bardsley, 1999)

daptomycin
DAPTOMYCIN
  • Cyclolipopeptide produced by S. roseosporus
  • Inhibits MRSA, VRE, penicillin-resistant Streptococcus pneumoniae, linezolide-resistant bacteria.
  • Discovered by Lillyin early 1980’s.
  • Licensed to Cubist in 1997.
  • Approved in 2003 and licensed to Chiron.
  • Disrupts plasma membrane function wothout entering cytoplasm; unique mode of action.
  • Bacteriocidal.
  • First new natural antibiotic in many years.

(Tally et al., 1999; Raja et al., 2003)

modified erythromycins
Modified Erythromycins
  • Clarithromycin (Biaxin® developed by Taisho)
  • Azithromycin (Zithromax® developed byPliva)
  • Telithromycin (Cetek® developed by Aventis) acts against resistant strains.

(Henninger, 2003)

current antitumor agents
Current Antitumor Agents
  • Daunorubicin
  • Doxorubicin
  • Bleomycins
  • Mitomycin C
  • Taxol
mylotarg gemtuzmab ozogamycin
Mylotarg (Gemtuzmab Ozogamycin)
  • Toxic enediyne antitumor agent calicheamycin attached to a humanized monoclonal antibody.
  • Directs enediyne to CD 33 protein antigen expressed by AML cells.
  • In 2000, approved for acute myeloid leukemia (AML).

(Borman, 2000)

rapamycin
Rapamycin
  • Discovered as antifungal agent.
  • Produced by Streptomyces hygroscopicus.
  • Unusual nitrogen-containing triene macrolide (polyketide) with very large 31-membered lactone ring.
  • Has antitumor activity.
  • Immunosuppressive potency somewhat greater than FK-506 and 150X cyclosporin A.
  • Toxicity less than cyclosporin A.
  • Precursors: acetate, propionate, methionine, pipecolate, shikimate.
the tacrolimus fk506 story
THE TACROLIMUS (FK506) STORY
  • Almost abandoned as a transplant immunosuppressant by Fujisawa because of dose-associated toxicity.
  • Dr. Thomas Starzl (U. Pittsburgh) rescued it by using lower doses , realizing it was 30-100x more active than cyclosporin A.
  • Introduced in Japan in 1993; USA in 1994.
  • Used for transplants of liver, heart, kidney, pancreas, lung, intestines, and for prevention of graft-vs.-host disease.
  • Topically used against a topic dermatitis, a widespread skin disease.

(T. Amaya et al., 2002)

actinomycete immunosuppressants have many activities
ACTINOMYCETE IMMUNOSUPPRESSANTS HAVE MANY ACTIVITIES
  • Approved for organ transplantation.
  • Antifungal.
  • Antitumor.
  • Reversal of multidrug resistance in mammalian cells.
  • Ascomycin is anti-inflammatory; SDZ ASM 981 in clinical tests vs. atopic dermtitis, allergic contact dermatitis and psoriasis. Also FK506.

(Arceci et al., 1992; Carle et al., 2000; Lehne et al., 2002; Robert and Jarry, 2003)

anti parasitic agents
Anti-parasitic Agents

2. Antihelmintic Agents

Previously only synthetic agents

Hygromycin, destomycin, myxin, etc. failed to compete

Avermectins (S. avermitilis)

Non-toxic

Non-antimicrobial

Macrocyclic lactones

Do not inhibit protein synthesis

Interfere with neurotransmission in invertebrates

1000x thiobenzole

10x other synthetics

Active vs. nematode and arthropod parasites in sheep, cattle, dogs, horses, swine

Ivermectin (22,23-dihydroavermectin B1)

Also insecticidal

bialaphos a herbicide
Bialaphos- A Herbicide
  • 1972 – Zähner group discovers phosphinothricyl-Ala-Ala from S. viridochromogenes: antibiotic against Gm+ and Gm- bacteria and Botyritis cinerea
  • 1973 – Independent discovery at Meiji Seiki of Bialaphos from S. hygroscopicus
  • Bialaphos =phosphinothricyl-Ala-Ala
  • Bialaphos is an herbicide with or without Ala-Ala
  • Bialaphos without Ala-Ala (= phosphinothricin) developed by Hoechst as herbicide (“glufosinate”)
acarbose
Acarbose
  • α-Glycosidase
  • Tetrasaccharide produced by Actinoplanes sp.
  • Used for Type I and Type II diabetes
  • Anti-glycosidase action delays uptake of glucose into intestine.

(Copsey et al.,1999; Wehmeier and Pipersberg, 2004)

desferal
DESFERAL
  • Desferri-ferrioxamine B
  • Discovered as an antibiotic
  • Fe (III)-Chelator from Streptomyces pilosus
  • Non-Toxic
  • Uses:
    • Iron overload (hemochromatosis) in acute iron intoxication
    • Iron overload from transfusions
    • Iron overload in Thalassemia
    • Aluminum overload in dialysis patients
    • Metal-desferal complex eliminated from body via kidneys.
lipstatin an enzyme inhibitor
LIPSTATIN, AN ENZYME INHIBITOR
  • Produced by Streptomyces toxytricini.
  • A pancreatic lipase inhibitor.
  • Combats diabetes and obesity.
  • Interferes with gastrointestinal absorption of fat.
  • Commercial product ORLISTAT is tetrahydrolipstatin.

(Weibel et al., 1987)

slide29
The microbe has come of age…there is no field of human endeavor, whether it be in industry or in agriculture, whether it be in the preparation of foodstuffs or in connection with problems of shelter and clothing, whether it be in the conservation of human and animal health and the combating of disease, where the microbe does not play an important and often a dominant part.

~S.A. Waksman, 1942