Synthesis of novel proxyphylline derivatives with dual Anti- Candida albicans and anticancer activity

Paweł Borowiecki , Patrycja Wińska , Maria Bretner , Małgorzata Gizińska , Mirosława Koronkiewicz , Monika Staniszewska


Three out of 16 newly synthesized 1,3-dimethylxanthine derivatives (proxyphylline analogues) exhibited consistencies between antifungal and anticancer properties. Proxyphylline possessing 1-(10H-phenothiazin-10-yl)propan-2-yl (6) and polybrominated benzimidazole (41) or benzotriazole moiety (42) remained selectively cidal against Candida albicans (lg R � 3 at conc. of 31, 36 and 20 mM, respectively) however not against normal mammalian Vero cell line in vitro (IC50 � 280 mM) and Galleria mellonella in vivo. These compounds also displayed moderate antineoplastic activity against human breast adenocarcinoma (MCF-7) cell line (EC50 ¼ 80 mM) and high against peripheral blood T lymphoblast (CCRF-CEM) (EC50 ¼ 6.3e6.5 mM). In addition, 6 and 42 exerted: (1) dual activity against fungal adhesion and damage mature biofilm; (2) necrosis of planktonic cells due to loss of membrane function and of structural integrity; (3) biochemical (inhibition of sessile cell respiration) and morphological changes in cell wall polysaccharide contents. Therefore, leading proxyphylline derivatives can be employed to prevent cancer-associated biofilm Candida infections.
Author Paweł Borowiecki (FC / IBC / DDTB)
Paweł Borowiecki,,
- Department Of Drug Technology And Biotechnology
, Patrycja Wińska (FC / IBC / DDTB)
Patrycja Wińska,,
- Department Of Drug Technology And Biotechnology
, Maria Bretner (FC / IBC / DDTB)
Maria Bretner,,
- Department Of Drug Technology And Biotechnology
, Małgorzata Gizińska
Małgorzata Gizińska,,
, Mirosława Koronkiewicz
Mirosława Koronkiewicz,,
, Monika Staniszewska
Monika Staniszewska,,
Journal seriesEuropean Journal of Medicinal Chemistry, ISSN 0223-5234, (A 40 pkt)
Issue year2018
Publication size in sheets1.3
Keywords in English1,3-Dimethylxanthines, Proxyphylline analogues, Fungicidal activity, Antibiofilm activity, Selective toxicity, Anticancer activity.
Languageen angielski
wdpb_publikacje_pliki_plik_publikacja_3429_org.pdf 3.53 MB
Score (nominal)40
ScoreMinisterial score = 40.0, 23-07-2018, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 23-07-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 4.519 (2) - 2016=4.187 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.