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A Short‐Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections
Author(s) -
Levina Aviva,
Pires Vieira Adriana,
Wijetunga Asanka,
Kaur Ravinder,
Koehn Jordan T.,
Crans Debbie C.,
Lay Peter A.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202005458
Subject(s) - cytotoxicity , chemistry , toxicity , cytotoxic t cell , cancer cell , cisplatin , pharmacology , drug , cell culture , cancer , glioma , biochemistry , cancer research , in vitro , medicine , biology , chemotherapy , organic chemistry , genetics
The chemistry and short lifetimes of metal‐based anti‐cancer drugs can be turned into an advantage for direct injections into tumors, which then allow the use of highly cytotoxic drugs. The release of their less toxic decomposition products into the blood will lead to decreased toxicity and can even have beneficial effects. We present a ternary V V complex, 1 ([VOL 1 L 2 ], where L 1 is N ‐(salicylideneaminato)‐ N ′‐(2‐hydroxyethyl)ethane‐1,2‐diamine and L 2 is 3,5‐di‐ tert ‐butylcatechol), which enters cells intact to induce high cytotoxicity in a range of human cancer cells, including T98g (glioma multiforme), while its decomposition products in cell culture medium were ≈8‐fold less toxic. 1 was 12‐fold more toxic than cisplatin in T98g cells and 6‐fold more toxic in T98g cells than in a non‐cancer human cell line, HFF‐1. Its high toxicity in T98g cells was retained in the presence of physiological concentrations of the two main metal‐binding serum proteins, albumin and transferrin. These properties favor further development of 1 for brain cancer treatment by intratumoral injections.