Theoretical Studies on the Inhibitory Activity of Levofloxacin-thiadiazole HDACi Conjugates to Histone Deacetylases

DOI

10.2991/bst-17.2018.3How to use a DOI?

Keywords

Levofloxacin-thiadiazole HDACi conjugates(LHCc), Histone deacetylases (HDACs), Inhibitory activity (pWi, i=1, 6), Electrotopological state indices (EK) of atom types, Quantitative structure-activity relationship (QSAR)

Abstract

Electrotopological state indices (EK) of atom types is used to describe the structures of 19 conjugates (LHCc) of levofloxacin-thiadiazole HDAC inhibitor (HDACi) and related to the inhibitory activity (pWi, i=1, 6) of LHCc against histone deacetylases(HDACs, HDAC1 and HDAC6). The optimal two-parameter(E17, E18) quantitative structure-activity relationships(QSAR) models are established by using leaps-and-bounds regression analysis for the inhibitory activities(pWi) of 19 above compounds to HDAC1 and HDAC6 along with the EK. The correlation coefficients (R2) and the leave-one-out (LOO) cross validation Rcv2 for the pW1 and pW6 models were 0.942 and 0.918, 0.943 and 0.919, respectively. The QSAR models have favorable correlation, as well as robustness and good prediction capability by R2, F, Rcv2, AIC, FIT, VIF tests. The results indicate that the molecular structural units: -NH2, -NH- are main factors which can affect the inhibitory activity(pWi)bioactivities of these compounds directly. Accordingly, it is suggested that the main interactions between HDACs inhibitor and HDACs are hydrophobic, hydrogen bond, and coordination compounds with Zn2+. This is consistent with the molecular docking results of document.

Copyright

© 2018, the Authors. Published by Atlantis Press.

Open Access

This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - CONF
AU  - Zi-Qiang Tang
AU  - Chang-Ning Liu
AU  - Yu-Sheng Liu
AU  - Hui Feng
AU  - Chang-Jun Feng
PY  - 2018/02
DA  - 2018/02
TI  - Theoretical Studies on the Inhibitory Activity of Levofloxacin-thiadiazole HDACi Conjugates to Histone Deacetylases
BT  - Proceedings of the 2017 2nd International Conference on Biological Sciences and Technology (BST 2017)
PB  - Atlantis Press
SP  - 18
EP  - 23
SN  - 2468-5747
UR  - https://doi.org/10.2991/bst-17.2018.3
DO  - 10.2991/bst-17.2018.3
ID  - Tang2018/02
ER  -