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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 4069839, 15 pages
Research Article

Dihydropyridine Derivatives as Cell Growth Modulators In Vitro

1Latvian Institute of Organic Synthesis, 21 Aizkraukles Str., Riga LV-1006, Latvia
2Laboratory for Oxidative Stress, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia

Correspondence should be addressed to Astrida Velena; vl.iso@adirtsa and Neven Zarkovic; rh.bri@civokraz

Received 9 December 2016; Accepted 20 February 2017; Published 3 April 2017

Academic Editor: Serafina Perrone

Copyright © 2017 Imanta Bruvere et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The effects of eleven 1,4-dihydropyridine derivatives (DHPs) used alone or together with prooxidant anticancer drug doxorubicin were examined on two cancer (HOS, HeLa) and two nonmalignant cell lines (HMEC, L929). Their effects on the cell growth (3H-thymidine incorporation) were compared with their antiradical activities (DPPH assay), using well-known DHP antioxidant diludine as a reference. Thus, tested DHPs belong to three groups: antioxidant diludine; derivatives with pyridinium moieties at position 4 of the 1,4-DHP ring; DHPs containing cationic methylene onium (pyridinium, trialkylammonium) moieties at positions 2 and 6 of the 1,4-DHP ring. Diludine and DHPs of group 3 exerted antiradical activities, unlike compounds of group 2. However, novel DHPs had cell type and concentration dependent effects on 3H-thymidine incorporation, while diludine did not. Hence, IB-32 (group 2) suppressed the growth of HOS and HeLa, enhancing growth of L929 cells, while K-2-11 (group 3) enhanced growth of every cell line tested, even in the presence of doxorubicin. Therefore, growth regulating and antiradical activity principles of novel DHPs should be further studied to find if DHPs of group 2 could selectively suppress cancer growth and if those of group 3 promote wound healing.