Podophyllotoxin: Critical Review, Commercial Development

This report provides a critical review of Podophyllotoxin, a lignan toxin derived from plants, exploring its history, biodiversity, and toxicity. The review examines the synthesis, biosynthesis, and medical applications of Podophyllotoxin, highlighting its use in traditional medicine and its derivatives, such as etoposide and teniposide, used in cancer treatment. It addresses the mode of action, including the inhibition of TOP2 and microtubule hindrance. The report also discusses the toxicity associated with Podophyllotoxin and compares it with other drugs in the market, such as TrichloroAceticAcid (TCA), Aldara cream, Sinecatechis, and Thuja, used for treating genital warts. The conclusion evaluates the suitability of Podophyllotoxin for commercial development, considering factors like cost of synthesis, biodiversity, and the presence of alternative treatments. The report uses Vancouver style of referencing.

Podophyllotoxin
CRITICAL REVIEW OF PODOPHYLLOTOXIN.
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INSTITUTION:
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Podophyllotoxin
Introduction.
Podophyllotoxin is a lignan toxin that is removed from the tubers and the shoots of podophyllum
classes. Plants which contain lignans have been in use for many decades as solutions for
traditional medicines by many communities. Plants containing high concentration of lignan
content were extensively in use China, Japan, and the East traditional medication, for instance,
Schizandraceae, Fraxinus sp. and Oleaeuropaea . [1]
It has originally been remote podophyllin, resin of Podophyllum shoot. Podophyllum emodi
which is also called Indian podophyllum is favored to Podophyllum peltatum or the
American podophyllum. The process of isolation is done using Chloroform (CHCl3), also called
trichloromethane which is easily available and thus making the cost of extraction more
economical.[2]
Biodiversity
There are three crucial half-synthetic byproducts of podophyllotoxin are etoposide, teniposide
and etoposide phosphate. The major target molecular of these anti-cancer medicines is TOP2.
[2]The elevated levels of DNA harm results from the adjustment of the cleavage complex, the
ternary complex between the medications, protein and the DNA. Hindrance of microtubule is a
second instrument of movement of podohyllotoxines in spite of the fact that etoposide and
teniposide doesn’t use this one however it influences the late S or G2 stage through TOP2
hesitance. For the most part the podophyllotoxin analogs display proficiency in germ cell tumor,
lung malignant growths, Hodgkin's ailment, non-Hodgkin's lymphoma and a few others. [2]
Toxicity.

Podophyllotoxin
The commonly known effects of podophyllotoxin ointment are typically inadequate to crossness
of soft tissue adjacent to the affected area, comprising scorching, soreness, soreness, irritating,
and bulge. Sore skin, itching and peeling skin can also be experienced and therefore application
should be done in a way to prevent the unaffected area. Podophyllin and or podophyllotoxin
should not be used by pregnant mothers because it causes embroytoxic. In addition, antimitotic
products are not classically suggested during pregnancy.[3].
Other drugs in the Market.
TrichloroAceticAcid (TCA)
This is a Podophyllotoxin substitute. TrichloroAceticAcid (TCA) is the most prevalent genital
warts drug. It destroys warts’ proteins, but it carries the risk of interfering with the proteins of
normal tissues as well. TCA is not commended for the curing of genitalia verrucae of the vagina,
cervix, or anus for it causes feeling of irritation.
Podophyllin is also used in treating genital warts. It is a non-standardized unsteady herb by-
product that has various lively components and the more active one being podophyllotoxin;
podophyllin 20% that contains 4-8 podophyllotoxin. This means that podophyllotoxin is more
pure and stable compared to podophyllin and therefore safer to use. [4]. other drugs used for
treating genital warts includes; Aldara cream (5%), which is categorized as a topical “immune
response modifier. Another drug is Sinecatechis .It is applied on top of the affected region. [5]
This genital warts drug is a compound found naturally in green tea leaves and is used primarily
to treat genital warts around the anus, and on the genitals. Thuja is also effective genital warts
drug which is a genus of coniferous trees, commonly known as “arborvitae.[6]

Podophyllotoxin
In conclusion, podophyllotoxin is suitable for commercial development because it is used in drug
manufacturing, pharmaceutical related products and in food manufacturing facilities but with
appropriate modifiers.[7]
Ref;

Podophyllotoxin
1. Efferth Thomas, Kuete Victor; Biodiversity, Natural Products and Cancer Treatment pg
356.
2. Paul E. Minnis, Wayne J. Elisens; Biodiversity and Native America pg 86.
3. Lewis R. Goldfrank, Robert S. Hoffman, Mary Ann Howland, Neal A. Lewin
Toxicologic Emergencies pg 584.
4. National Center for Biotechnology Information. PubChem Database. Podofilox,
CID=10607, https://pubchem.ncbi.nlm.nih.gov/compound/Podofilox .
5. Marques JV, Kim KW, Lee C, Costa MA, May GD, Crow JA, Davin LB, Lewis NG.
Next generation sequencing in predicting gene function in podophyllotoxin biosynthesis.
Journal of Biological Chemistry. 2013 Jan 4;288(1):466-79.
6. Guerram M, JIANG ZZ, Zhang LY. Podophyllotoxin, a medicinal agent of plant origin:
past, present and future. Chinese journal of natural medicines. 2012 May 1;10(3):161-9.
7. Lv M, Xu H. Recent advances in semisynthesis, biosynthesis, biological activities, mode
of action, and structure-activity relationship of podophyllotoxins: an update (2008-2010).
Mini reviews in medicinal chemistry. 2011 Sep 1;11(10):901-9.