title: δ-Carbolines and their ring-opened analogs: synthesis and evaluation against fungal and bacterial opportunistic pathogens.
abstract: Previous studies have indicated that the δ-carboline (2) ring system derived from the natural product cryptolepine (1) may represent a pharmacophore for anti-infective activity. This paper describes the design and synthesis of a small library of substituted δ-carbolines and the evaluation of the anti-fungal and anti-bacterial activities. An evaluation of the anti-bacterial activity of a previously reported library of ring-opened analogs was also conducted to provide an opportunity to test the hypothesis that both group of compounds may have the same biological target. Results indicate that against a selected group of fungal pathogens, substituted δ-carbolinium analogs displayed higher potency and several fold lower cytotoxicity than cryptolepine the parent natural product. Both the δ-carbolinium compounds and their ring-opened analogs, exhibited equally high anti-bacterial activity against the selected pathogens and especially against the gram positive bacteria evaluated.
authors: Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA.
authors: Tryphon K
authors: TK
authors: Mazu
authors: Jagan R
authors: JR
authors: Etukala
authors: Melissa R
authors: MR
authors: Jacob
authors: Shabana I
authors: SI
authors: Khan
authors: Larry A
authors: LA
authors: Walker
authors: Seth Y
authors: SY
authors: Ablordeppey
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000472:pathogenicity; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D005658:Fungi / Q000187:drug effects* / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002243:Carbolines