Marine organisms and other novel natural sources of new cancer drugs Gilberto Schwartsmann
South-American Office for Anticancer Drug Development (SOAD), Comprehensive Cancer Centre (CINCAN), The Lutheran University (ULBRA) & Postgraduate Course in Medicine (UFRGS), Porto Alegre, Brazil Introduction
Man has always relied on nature for survival. Since
ancient times, nature has been our main source of
food, protection, clothing, transportation and remedies
[1,2]. This can be illustrated by the number
of natural product derived agents currently in use
in routine medical practice (Table 1) [3-5]. In addition
to plant-derived compounds, microorganisms
constitute a very important source of novel bioactive
agents. They have contributed to the medical
armamentarium with antibiotics such as penicillins,
aminoglycosides and cephalosporins, which represent
landmarks in the history of human therapeutics
[6,7]. Although marine compounds are yet underrepresented
in routine clinical practice, it can be
anticipated that aquatic environment may become a
potentially valuable source of novel compounds, as
the world's oceans cover about 70% of the earth's
surface and all except 2 of the 28 major animal phyla
are represented there [8-11].
Anti-cancer agents derived from natural sources
Several new anticancer agents that entered the market
in the 1990s were obtained from natural sources
(Table 2) [12,13]. There is also a significant number
of naturally derived new anticancer candidate compounds
that are currently undergoing preclinical and
early clinical development (Table 3) [3,14].
Plant-derived compounds, in particular, have .a
special place in the anticancer therapy (Table 4)
[15,16]. The Vinca alkaloid vincristine (isolated from
Catharanthus roseus) is part of various curative regimens
in patients with leukaemia and lymphoma
[17,18]. Similarly, the epipodophyllotoxin derivative,
etoposide (extracted from the mandrake plant
Podophyllum peltatum and the wild chervill P. emodi)
is included in drug regimens that produce a significant
number of cures in patients with germ-cell
tumours [19,20]. The taxoids (extracted from the
bark of the Taxaceae Taxus brevifolia, T. canadensis,
or T. baccata) and the camptothecins (derived from
the bark and wood of the Nyssacea Camptotheca
acuminata) have also significant anti-solid tumour
Drugs developed from plant sources
Drug Medical use Plant source
For atrial fibrillation and CHF
For malaria prophylaxis
For motion sickness
Relaxant in surgery
Sty rax tonkinensis
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Anticancer drugs developed from plant sources
Drug Medical use Plant source
Etoposide Testicular tumours, small cell lung cancer
Teniposide Paediatric acute lymphoblastic leukaemia
Vinblastine Hodgkin's disease, non-Hodgkin's lymphoma, carcinoma of the testis, Kaposi's sarcoma, choriocarcinoma, breast cancer
Vincristine Acute leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, rhabdomyosarcoma, Wilm's tumour
Vindesine Investigational; modest activity in Hodgkin's disease, non-Hodgkin's lymphoma, leukaemias, non-small cell lung cancer, and breast cancer
Vinorelbine Activity in breast and non-small cell lung cancer Paclitaxel...
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7 Samuelsson G. Drugs of Natural Origin. Swedish Pharmaceutical
Press, Stockholm, 1992.
The Cairns Conference, Australia, 25-28 March, 1996.
OECD Publications, Paris, 1997, pp 253.
(eds), Natural Products and Drug Development Balliere, Tindall,
and Cox, London, 1984, pp 8-98.
14 Hartwell JL. Plants used against cancer. A survey. Quartennan
Publications, Lawrence, 1982.
Practice, 4th edn. Lippincott, Philadelphia, 1991, pp 325-417.
28 DiMarco A, Gaetani M, Scarpinato B. Adriamycin (NSC
123127) a new antibiotic with antitumor activity
31 Jessup JM, McGinnis LS, Winchester DP, et al. Clinical
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