Structure-activity relationships of dimeric Catharanthus alkaloids. 1. Deacetyl vinblastine amide (vindesine) sulfate

Barnett, Charles J.; Cullinan, George J.; Gerzon, Koert; Hoying, Richard C.; Jones, William E.; Newlon, W. M.; Poore, Gerald A.; Robison, R. L.; Sweeney, Martin J.

doi:10.1021/jm00199a016

Cited by 131 publications

(41 citation statements)

References 4 publications

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“…Vinblastine and vincristine are two natural alkaloids from Catharanthus roseus or Vinca rosea used as major drugs in the treatment of lymphoma and leukemia, respectively (Barnett et al 1978). C. roseus L. (Apocynaceae) Madagascar Periwinkle is found to contain a very large number of alkaloids, about 100 of which have been isolated so far (Verpoorte et al 1997;Hughes and Shanks 2002;Samuelsson 1999).…”

Section: Vinca Alkaloidsmentioning

confidence: 99%

Endophytic fungi: novel sources of anticancer lead molecules

Chandra

2012

Appl Microbiol Biotechnol

219

120

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Cancer is a major killer disease all over the world and more than six million new cases are reported every year. Nature is an attractive source of new therapeutic compounds, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, camptothecin, podophyllotoxin, and taxol. Production of a plant-based natural drug is always not up to the desired level. It is produced at a specific developmental stage or under specific environmental condition, stress, or nutrient availability; the plants may be very slow growing taking several years to attain a suitable growth phase for product accumulation and extraction. Considering the limitations associated with the productivity and vulnerability of plant species as sources of novel metabolites, microorganisms serve as the ultimate, readily renewable, and inexhaustible source of novel structures bearing pharmaceutical potential. Endophytes, the microorganisms that reside in the tissues of living plants, are relatively unstudied and offer potential sources of novel natural products for exploitation in medicine, agriculture and the pharmaceutical industry. They develop special mechanisms to penetrate inside the host tissue, residing in mutualistic association and their biotransformation abilities opens a new platform for synthesis of novel secondary metabolites. They produce metabolites to compete with the epiphytes and also with the plant pathogens to maintain a critical balance between fungal virulence and plant defense. It is therefore necessary that the relationship between the plants and endophytes during the accumulation of these secondary metabolites is studied. Insights from such research would provide alternative methods of natural product drug discovery which could be reliable, economical, and environmentally safe.

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Section: Vinca Alkaloidsmentioning

confidence: 99%

Endophytic fungi: novel sources of anticancer lead molecules

Chandra

2012

Appl Microbiol Biotechnol

219

120

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“…Vinblastine is mainly used to treat advanced Hodgkins lymphoma and testicular, bladder and breast cancers. These two vinca alkaloids differ structurally by only a single methyl substitution in the vindoline ring, yet they display remarkably different activities and toxicity profiles [178,179] .…”

Section: Vinca Alkaloidsmentioning

confidence: 99%

Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response

Mellor¹,

Callaghan²

2008

Pharmacology

150

100

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Inherent and acquired resistance pathways account for the high rate of failure in cancer chemotherapy. The mechanisms or pathways mediating resistance may be classified as pharmacokinetic (i.e. alter intratumour drug exposue) or pharmacodynamic (i.e. failure to elicit cytotoxicity). More often than not, the resistant phenotype is characterised by alterations in multiple pathways. Consequently, the pathways may act synergistically or generate a broad spectrum of resistance to anticancer drugs. There has been a great deal of systematic characterisation of drug resistance in vitro. However, translating this greater understanding into clinical efficacy has rarely been achieved. This review explores the phenomenon of drug resistance in cancer and highlights the gap between in vitro and in vivo observations. This gap presents a major obstacle in overcoming drug resistance and restoring sensitivity to chemotherapy.

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“…This was the impetus to compare them on the basis of the time required to block axoplasmic transport in uitro. In our first work on the effect of these agents, VCR blocked axoplasmic transport i n uitro sooner than VLB (Ochs and Worth, 1975) or a new vinca alkaloid derivative, vindesine (VDS) (Barnett et al, 1978).…”

Section: Introductionmentioning

confidence: 99%

Block of axoplasmic transport in vitro by vinca alkaloids

1980

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The three potent antimitotic vinca alkaloids: vincristine (VCR), vinblastine (VLB), and vindesine (VDS) were compared for their effect in blocking axoplasmic transport in vitro using a desheathed preparation of the peroneal branch of cat sciatic nerve. A range of vinca alkaloid concentrations from 1-100 microM was examined. The relative order of potency in blocking axoplasmic transport was VCR greater than VLB greater than VDS at a concentration of 25 microM. At the higher concentrations block occurred so rapidly that a statistically significant difference between these agents could not be obtained. The relation of vinca block to the transport mechanism is discussed.

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Structure-activity relationships of dimeric Catharanthus alkaloids. 1. Deacetyl vinblastine amide (vindesine) sulfate

Cited by 131 publications

References 4 publications

Endophytic fungi: novel sources of anticancer lead molecules

Endophytic fungi: novel sources of anticancer lead molecules

Resistance to Chemotherapy in Cancer: A Complex and Integrated Cellular Response

Block of axoplasmic transport in vitro by vinca alkaloids

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