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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-9827
Vol. 8, Num. 5, 2009, pp. 383-384
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Tropical Journal of Pharmaceutical Research, June 2002; 1 (1): 63-22
Tropical Journal of Pharmaceutical Research, Vol. 8, No. 5, October, 2009, pp. 383-384
Guest Editorial
Natural Products Regain Attention in
Oncology
Samuel X. Qiu
Ph.D., CAS ‘BRJH’ Endowed Professor, Natural Product Medicinal Chemistry
& Drug Discovery, South China Botanical Garden, Chinese Academy of Sciences Guangzhou, 510650, China, Email: sxqiu@scbg.ac.cn
Code Number: pr09049
Cancer is
a dreadful disease caused by abnormal and uncontrolled cell division. About
6 million new incidences of cancer are reported yearly worldwide. Nature has
given man a variety of useful sources of remedies to cure a number of diseases.
Since ca 1500, natural products (NP; here the term is restricted to
small-molecule secondary metabolites) have played a significant role in drug
discovery and development, especially agents active against cancer and
infectious diseases [1].
An
analysis of new and approved drugs for cancer by the United States Food and
Drug Administration (FDA) over the period 1981 - 2002 showed that 62 % of
cancer drugs were of natural origin. Natural compounds possess highly diverse
and complex molecular structures, compared to synthetic small-molecule drugs,
and often provide highly specific biological activities that are likely derived
from their rigidity and high number of chiral centres.
Since the
discovery of novel anticancer agents doxorubicin and mitomycin in 1961, and
bleomycin and vincristine in 1969 [2] - natural products have been the
cornerstone of cancer treatment. However, since the late 1990s, with the rapid
expansion of the use of monoclonal antibodies and synthetic protein (peptide)
kinase inhibitors against cancer cells, anticancer natural products fell out of
favour in the pharmaceutical industry. This situation did not change much until
2007. However, with the approval of three new drugs derived from
microorganisms, including alvespimycin and salinosporamide [3] and the new
formulations of known natural product-derived drugs (nanoparticle formulations,
for example), there has been a wave of renewed interest in natural products in
oncology. The recent approval of the microtubule-targeted epothilone
derivative, ixabepilone (Ixempra®); the DNA-alkylating marine
alkaloid, trabectedin (Yondelis®) and the mTOR protein kinase
inhibitor, temsirolimus (Torisel®) is emblematic of the evolution in
this area which combines the well-established findings of conventional
cytotoxic agents and emerging molecularly-targeted therapeutics. The
aforementioned examples also highlight the increasing significance of microbial
sources for the discovery of natural-product drugs, although novel molecules of
marine and terrestrial origins are regularly approved for the treatment of
cancer.
Bioassay-guided
fractionation and isolation is still a gold standard for the discovery of
natural product anticancer agents, which depends mainly on the quality of the
NP library with structural diversity, as well as the well-defined
cancer-specific molecular targets and bioassay systems set up to monitor the
compounds of interest. Not all molecular targets are well adapted to the
identification of active NPs. For example, the initial screening of natural
extracts against purified protein kinases is generally difficult due to a
higher rate of false positives compared to synthetic chemical libraries, and
this is caused primarily by non-specific interaction with accompanying
interfering compounds, such as polyphenols and tannin, which are commonly
present in all plant extracts. Cell-based assays are more suitable for
screening NP extracts [4]. The development of highly robust and sensitive high
throughput screening (HTS) assays is a key to minimising expenditures on NP
anticancer drug discovery.
It can be
envisioned that conventional cytotoxic anticancer agents will still remain the
favorites of oncology clinicians, but with a preference for NP anticancer drugs
targeting areas other than the tubulin/microtubulin network or the DNA
replication machinery. It is expected that increasing numbers of anticancer
natural products from plants, marine and microorganisms with desirable efficacy
and side-effect profiles will be discovered in years to come. With advances in
cell and molecular biology, detailed understanding of the mechanisms of action
of NP anticancer drugs will, in turn, aid research in cancer biology and
oncology, with these active natural products serving as bio-probes through an
approach known as chemical biology or chemical genetics [5].
References
1.
Butler MS.
Natural products to drugs: natural product-derived compounds in clinical
trials. Nat. Prod. Rep 2008; 25: 475-516.
2.
Blum RH,
Carter SK. Adriamycin. A new anticancer drug with significant clinical
activity. Ann Intern Med 1974; 80: 249-259.
3.
Ganesa A.
The impact of natural products upon modern drug discovery. Curr Opin Chem Biol
2008; 12: 306-317.
4.
Harvey AL.
Natural products as a screening resource. Curr Opin Chem Biol 2007; 11:
480-484.
5.
Spring DR.
Chemical genetics to chemical genomics: small molecules offer big insights.
Chem. Soc. Rev. 2005; 34: 472-482.
© Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria.
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