Probing the N-5 region of the indoloquinoline alkaloid, cryptolepine for anticryptococcal activity.
N-5 Alkylated analogues of cryptolepine were synthesized and tested for anticryptococcal activity. Evidence provided in this study suggests that the active form of cryptolepine consists of the flat tetracyclic aromatic ring with the methyl group on the N-5 atom. It was also found that changes in the electronic density around the N-5 atom do not appear to affect activity. Steric hindrance of the N-5 substituents seems to decrease activity. Through systematic modification of the N-5 alkyl groups, o-phenylpentyl group was shown to possess the highest potency thus far.
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Division of Basic Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307, USA.
Fan
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Clark
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D000470:Alkaloids / Q000737:chemistry*; D000478:Alkylation; D000935:Antifungal Agents / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D026121:Indole Alkaloids; D007211:Indoles; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011804:Quinolines; D013696:Temperature
D000470:Alkaloids; D000935:Antifungal Agents; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C024015:cryptolepine