TITLE:
Activity Trends in Desoxy Anthrapyrazoles: The Influence of Molar Volume, Polarizability and Lipophilicity of N2 C5 Side Chains on Their Anticancer Response
AUTHORS:
Howida A. Hashim, Mohamed Osman M. A. El-Fakii, Ahmed Elsadig M. Saeed
KEYWORDS:
Polarizability, Molar Volume, Lipophilicity, Anthrapyrazoles, Murine
JOURNAL NAME:
Computational Chemistry,
Vol.8 No.2,
March
3,
2020
ABSTRACT: QSAR methodology was used to assess the effects of lipophilicity (logP),
molar volume (MV) and polarizability (pl) of the side chains at N2 and C5 of 20 known desoxy anthrapyrazoles on their in
vitro anticancer activity expressed as the negative logarithm of the
inhibitory concentration of 50% of L1210 murine leukemia cell line (1/logIC50).
The main data set shows poor correlations between biological response and the
descriptors with exception of MV of the C5 side chain,
where a moderate correlation was discerned ( =0.60, n = 18,
two outliers). To extract more information regarding mechanism, the
main data set was visually classified to three clusters depending on N2 side chain. Cluster 1 containing six 5-substituted
2-[(2-hydroxyethyl) amino] ethyl anthrapyrazoles; cluster 2 contains ten 5-subsitutes 2-(diethyl
amino) ethyl anthrapyrazoles and cluster 3 contains four anthrapyrazoles
with miscellaneous substituents at both N2 and C5.
For cluster 1, MV and pl of C5 show high correlation
with biological response (R2’s = 0.75 and 0.72
respectively) while logP gives
a weak correlation (R2 = 0.44). For cluster 2, the
correlations of logP and pl of C2side chain are higher (=0.66 and 0.62 respectively) compared with MV (=0.16). Cluster 3 shows very poor correlation with all
descriptors (~0.3). This indicates mechanistic distinction between the three clusters.
Derived descriptors which represent the difference between the descriptors of N2 and C5 side chains where used to explore the presence of
interplay between these descriptors in affecting variability of the biological
response.