Abstract
Isosteres of cryptolepine (1) were synthesized and evaluated for their antiinfective activities. Overall, the sulfur isostere, 5-methyl benzothieno[3,2-b]quinolinium salt (5b), was equipotent to 1 and has shown no cytotoxicity at 23.8 microg/mL. Compound 5b was also found to have a broad spectrum of activity. Both the carbon and oxygen isosteres were less potent than cryptolepine. A limited library of 2-substituted analogs of 5b has been synthesized and evaluated in antifungal screens but did not show increase in potency compared to the unsubstituted 5b. Similarly, evaluation of tricyclic benzothieno[3,2-b]pyridines while showing promise in individual screens did not produce an overall increase in potency. Overall, the evaluation of the activities of 5b compared with standard antifungal/anti-protozoal agents suggests that the benzothienoquinoline scaffold could serve as a lead for optimization.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alkaloids / chemical synthesis*
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Alkaloids / pharmacology*
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Animals
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / pharmacology*
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Antimalarials / chemical synthesis
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Antimalarials / pharmacology
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Antiparasitic Agents / chemical synthesis
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Antiparasitic Agents / pharmacology
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Bacteria / drug effects
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Cell Line
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Cell Survival / drug effects
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Chemical Phenomena
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Chemistry, Physical
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Chlorocebus aethiops
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Fungi / drug effects
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Humans
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Indicators and Reagents
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Indole Alkaloids
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Indoles / chemical synthesis*
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Indoles / pharmacology*
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Isomerism
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Leishmania donovani / drug effects
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Magnetic Resonance Spectroscopy
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Mice
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Microbial Sensitivity Tests
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Plasmodium falciparum / drug effects
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Quinolines / chemical synthesis*
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Quinolines / pharmacology*
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Structure-Activity Relationship
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Vero Cells
Substances
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Alkaloids
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Anti-Infective Agents
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Antimalarials
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Antiparasitic Agents
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Indicators and Reagents
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Indole Alkaloids
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Indoles
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Quinolines
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cryptolepine