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 - [National Medicines Institute, Warsaw]
Małgorzata Gizińska,,
, Mirosława Koronkiewicz - [National Medicines Institute, Warsaw]
Mirosława Koronkiewicz,,
, Monika Staniszewska - [National Medicines Institute, Warsaw]
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.
ASJC Classification1605 Organic Chemistry; 3002 Drug Discovery; 3004 Pharmacology; 2700 General Medicine
Languageen angielski
wdpb_publikacje_pliki_plik_publikacja_3429_org.pdf 3.53 MB
Score (nominal)40
ScoreMinisterial score = 40.0, 23-09-2019, ArticleFromJournal
Publication indicators WoS Citations = 3; Scopus Citations = 3; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.562; WoS Impact Factor: 2017 = 4.816 (2) - 2017=4.527 (5)
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