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Antifungal, anticancer, and docking studies of colchiceine complexes with monovalent metal cation salts
Author(s) -
Kurek Joanna,
KwaśniewskaSip Patrycja,
Myszkowski Krzysztof,
Cofta Grzegorz,
Barczyński Piotr,
Murias Marek,
Kurczab Rafał,
Śliwa Paweł,
Przybylski Piotr
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13583
Subject(s) - chemistry , potency , antifungal , stereochemistry , metal , colchicine , dihedral angle , docking (animal) , combinatorial chemistry , biochemistry , in vitro , organic chemistry , biology , molecule , microbiology and biotechnology , medicine , genetics , hydrogen bond , nursing
Abstract Complexes of colchiceine with monovalent cation perchlorates and iodides have been obtained and characterized by spectroscopic methods. DFT and spectroscopic studies reveal that the dihedral angle ω 1‐1a‐12‐12a , crucial for colchicine biological mechanism of action, that is, binding to tubulins depends on the diameter of the complexed metal cation. Biological tests indicated no antifungal properties of colchicine (it was active only toward A.pullulans ), in contrast to its derivative—(colchiceine). Complexation of colchiceine with metal cations improved significantly the antifungal potency, even below MIC <1 μg/ml. The colchiceine complexes were more potent than colchiceine, and some of them were even more potent than the fungicidal standard IPBC . The highest potency of colchiceine complexes was noted against A. pullulans ( MIC = 0.5 μg/ml). In contrast to the findings concerning antifungal potency, the anticancer studies showed complexes of colchicine more active (~ IC 50 = 2 nM ) than those of colchiceine (~ IC 50 = 6 μM). MDA ‐ MB ‐231 breast cancer cell lines and human lung fibroblasts CCD 39Lu were also tested.