title: Searching for new derivatives of neocryptolepine: synthesis, antiproliferative, antimicrobial and antifungal activities.
abstract: A series of novel amino acid and dipeptide derivatives of neocryptolepine were synthesized and tested for their antimicrobial, antifungal and antiproliferative activity in vitro against cancer cell lines (KB, A549, MCF-7, LoVo) and normal mice fibroblast cells (BALB/3T3). Biological evaluation revealed that almost all of the new compounds displayed high antiproliferative activity against the tested cells and moderate to potent antibacterial activities. Interestingly, these compounds were active against Candida albicans biofilms at doses significantly lower than those required against free-floating planktonic fungal cells. The most promising compounds are derivatives with glycine and L-proline as a substituent both at 2 and at 9 position of 5H-indolo[2,3-b]quinoline. In general, these new compounds (2a, 3a, 6a and 7a) showed the highest dual action against cancer lines and infectious pathogenic microbes in vitro.
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland. Electronic address: k.sidoryk@ifarm.eu.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sidoryk
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaromin
authors.affiliation: Department of Medicine, Section of Infectious Diseases, 4125 Microbial Sciences Building, 1550 Linden Dr., University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Edward
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Świtalska
authors.affiliation: Medical University of Warsaw, Department of Pharmaceutical Microbiology, 3 Oczki St., 02-007 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefańska
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland; Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Cmoch
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Zagrodzka
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szczepek
authors.affiliation: Division of Organic Technology, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
authors.forename: Wanda
authors.initials: W
authors.lastname: Peczyńska-Czoch
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St., 53-114 Wroclaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: Department of Lipids and Liposomes, Faculty of Biotechnology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Kozubek
authors.affiliation: Department of Medicine, Section of Infectious Diseases, 4125 Microbial Sciences Building, 1550 Linden Dr., University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zarnowski
authors.affiliation: Department of Medicine, Section of Infectious Diseases, 4125 Microbial Sciences Building, 1550 Linden Dr., University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Kaczmarek
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D011804:Quinolines; C414982:neocryptolepine
keywords: Amino acid; Antimicrobial activity; Antiproliferative activity; Biofilm; NMR; Neocryptolepine; Peptide