title: Biological activity of novel macrocyclic alkaloids (budmunchiamines) from Albizia amara detected on the basis of interaction with DNA.
abstract: Extracts derived from Albizia amara were found to demonstrate activity in a recently developed hplc system designed to detect compounds capable of interacting with DNA. Further investigation led to the procurement of four sets of alkaloid isolates X1-X4 that were found to be macrocyclic pithecolobine alkaloids. All four isolates interacted with calf thymus DNA and were generally cytotoxic with a battery of cultured mammalian cells. As determined with Salmonella typhimurium strain TM677, isolates X1 and X3 were bactericidal, but not mutagenic. Isolate X1 was found to inhibit the catalytic activity of DNA polymerase, RNA polymerase, and HIV-1 reverse transcriptase. With DNA polymerase, the reaction was shown to be inhibited in a manner that was competitive with respect to DNA. In addition, isolate X1 inhibited each of the following: platelet aggregation, human lymphocyte transformation, phorbol-ester-induced chemiluminescence with human granulocytes, and cyclooxygenase activity. Detection of these alkaloids on the basis of their interaction with DNA exemplifies the validity of this approach.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60612.
authors.forename: W
authors.initials: W
authors.lastname: Mar
authors.forename: G T
authors.initials: GT
authors.lastname: Tan
authors.forename: G A
authors.initials: GA
authors.lastname: Cordell
authors.forename: J M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: K
authors.initials: K
authors.lastname: Jurcic
authors.forename: F
authors.initials: F
authors.lastname: Offermann
authors.forename: K
authors.initials: K
authors.lastname: Redl
authors.forename: B
authors.initials: B
authors.lastname: Steinke
authors.forename: H
authors.initials: H
authors.lastname: Wagner
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004247:DNA; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004354:Drug Screening Assays, Antitumor; D007887:Fabaceae / Q000737:chemistry; D006098:Granulocytes / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D008214:Lymphocytes / Q000187:drug effects; D009153:Mutagens / Q000302:isolation & purification / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors; D010946:Plants, Medicinal; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D018894:Reverse Transcriptase Inhibitors; D012486:Salmonella typhimurium / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D009153:Mutagens; D019384:Nucleic Acid Synthesis Inhibitors; D010975:Platelet Aggregation Inhibitors; D018894:Reverse Transcriptase Inhibitors; D004247:DNA; D011451:Prostaglandin-Endoperoxide Synthases; D012321:DNA-Directed RNA Polymerases