Abstract
Several ring-contracted analogues of the antitumor agent etoposide have been prepared. The synthesis of the simple indanyl system 3 is described along with two bicyclic systems of general structure 4 prepared through a stereoselective allylation of the keto-ester 6. A cis-fused lactone analogue 5, which is isomeric with the etoposide aglycone, has been synthesized via a dialkylation of the indene-2-carboxylate anion. Regiochemical and stereochemical results of these alkylations are described. The cytotoxicity of these derivatives toward several tumor cell lines is described and generally follows the structure-activity relationships known for the agent podophyllotoxin (2).
MeSH terms
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Adenocarcinoma / drug therapy
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / therapeutic use
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Carcinoma / drug therapy
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Chemical Phenomena
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Chemistry
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Colonic Neoplasms / drug therapy
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Etoposide / analogs & derivatives
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Etoposide / chemistry
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Etoposide / therapeutic use
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Humans
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Indans / chemistry
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Indans / therapeutic use
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Leukemia P388 / drug therapy
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Lung Neoplasms / drug therapy
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Mice
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Molecular Structure
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Podophyllotoxin / analogs & derivatives
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Podophyllotoxin / chemical synthesis*
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Podophyllotoxin / chemistry
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Podophyllotoxin / therapeutic use
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Indans
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Etoposide
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Podophyllotoxin