Abstract
A series of 47 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for anti-lung cancer activity by screening against the melanoma cancer cell line B16-F10. Five compounds have been found to possess significant activity, more so than a standard therapy, Gemcitabine. Moreover, one compound has been found to have an activity around 70-fold that of Gemcitabine and has a favourable selectivity index of greater than 125. Furthermore, initial studies have revealed this compound to be metabolically stable and thus it represents a lead for further optimisation towards a novel treatment for lung cancer.
Keywords:
Anti-cancer; Lung cancer; Minor Groove Binders.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / pharmacology*
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Biological Products / chemistry
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Biological Products / isolation & purification
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Biological Products / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemistry
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Deoxycytidine / isolation & purification
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Deoxycytidine / pharmacology
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Distamycins / chemistry
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Distamycins / isolation & purification
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Distamycins / pharmacology*
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Gemcitabine
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / pathology
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Molecular Structure
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Structure-Activity Relationship
Substances
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Antineoplastic Agents, Phytogenic
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Biological Products
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Distamycins
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Deoxycytidine
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stallimycin
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Gemcitabine