A series of pyrrolidinoindolines have been synthesized as debromoflustramine B (4a) analogues for their evaluation as cholinesterase inhibitors. Structure-activity studies of this series revealed the optimum pharmacophoric elements required for activity and resulted in the discovery of selective butyrylcholinesterase inhibitors with micromolar potency. Biological testing demonstrated that (-)-4a was 7500 times more potent than its enantiomer (+)-4b. The most active inhibitor against BChE in the series was demethyldebromoflustramine B (5a), with an IC50 value of 0.26 microM. X-ray crystallography of 15 and docking studies of selected compounds into human BChE (PDB 1POI) are presented. Molecular modeling studies showed that pi-hydrogen bond, classical hydrogen bond, and cation-pi interactions are critical for optimum potency.

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Physicochemical properties of the hexosomes containing ketoconazole are important for topical mycosis treatment administration, conditions of storage, and for its incorporation into the formulation of semi-solid dosage forms.

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A series of 1,3a,8-alkylpyrrolidinoindolines have been synthesized. The scope and limitations of the alkylation of starting methyl oxindol-3acetates are explored employing electron-rich and electron-poor alkylating agents. Hydrolysis and reductive lactonization of the resulting carboxylic γ-oxindolic acid derivatives proceeds with good yields to afford 2-oxofuroindolines providing ready access to the pyrrolidinoindoline derivatives.