Version 1
: Received: 10 May 2021 / Approved: 11 May 2021 / Online: 11 May 2021 (15:35:00 CEST)
How to cite:
Bieszczad, B.; Garbicz, D.; Świtalska, M.; Dudek, M. K.; Warszycki, D.; Wietrzyk, J.; Grzesiuk, E.; Mieczkowski, A. Novel Vorinostat Analogues with Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity Against Leukemias and Lymphomas. Preprints2021, 2021050251. https://doi.org/10.20944/preprints202105.0251.v1
Bieszczad, B.; Garbicz, D.; Świtalska, M.; Dudek, M. K.; Warszycki, D.; Wietrzyk, J.; Grzesiuk, E.; Mieczkowski, A. Novel Vorinostat Analogues with Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity Against Leukemias and Lymphomas. Preprints 2021, 2021050251. https://doi.org/10.20944/preprints202105.0251.v1
Bieszczad, B.; Garbicz, D.; Świtalska, M.; Dudek, M. K.; Warszycki, D.; Wietrzyk, J.; Grzesiuk, E.; Mieczkowski, A. Novel Vorinostat Analogues with Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity Against Leukemias and Lymphomas. Preprints2021, 2021050251. https://doi.org/10.20944/preprints202105.0251.v1
APA Style
Bieszczad, B., Garbicz, D., Świtalska, M., Dudek, M. K., Warszycki, D., Wietrzyk, J., Grzesiuk, E., & Mieczkowski, A. (2021). Novel Vorinostat Analogues with Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity Against Leukemias and Lymphomas. Preprints. https://doi.org/10.20944/preprints202105.0251.v1
Chicago/Turabian Style
Bieszczad, B., Elżbieta Grzesiuk and Adam Mieczkowski. 2021 "Novel Vorinostat Analogues with Improved HDAC Inhibition, Stronger Cytotoxic Effect and Higher Selectivity Against Leukemias and Lymphomas" Preprints. https://doi.org/10.20944/preprints202105.0251.v1
Abstract
Histone deacetylase (HDAC) inhibitors are class of drugs used in the cancer treatment. Here, we developed a library of 19 analogues of Vorinostat, an HDAC inhibitor used in lymphomas treatment. In Vorinostat, we replaced the hydrophobic phenyl group with various tricyclic ‘caps’ possessing a central, eight-membered, heterocyclic ring, and investigated the HDAC activity and cytotoxic effect on the cancer and normal cell lines. We found that three out of the 19 compounds, based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds, showed better HDACs inhibition than the referenced Vorinostat. In leukemic cell line MV4-11 and in lymphoma cell line – Daudi three compounds showed lower IC50 values than Vorinostat. These compounds had higher activity and selectivity against MV4-11 and Daudi cell lines than reference Vorinostat. We also observed a strong correlation between HDACs inhibition and the cytotoxic effect. Cell lines derived from solid tumors: A549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) as well as reference Balb/3T3 (normal murine fibroblasts) were less susceptible to compounds tested. Developed derivatives show superior properties than Vorinostat, thus they are applicable as selective agents for leukemia and lymphoma treatment.
Copyright:
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.