Searching for new derivatives of neocryptolepine: synthesis, antiproliferative, antimicrobial and antifungal activities

• Published in: European journal of medicinal chemistry 2014-05, Vol.78, p.304-313
• Main Authors: Sidoryk, Katarzyna, Jaromin, Anna, Edward, Jessica A, Świtalska, Marta, Stefańska, Joanna, Cmoch, Piotr, Zagrodzka, Joanna, Szczepek, Wojciech, Peczyńska-Czoch, Wanda, Wietrzyk, Joanna, Kozubek, Arkadiusz, Zarnowski, Robert, Andes, David R, Kaczmarek, Łukasz
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; BALB 3T3 Cells; Biofilms - drug effects; Candida albicans - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fibroblasts - drug effects; Humans; MCF-7 Cells; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Molecular Structure; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.03.060

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.