Author(s)

Howida A. Hashim^1*, Mohamed Osman M. A. El-Fakii², Ahmed Elsadig M. Saeed³

¹Department of Science, Faculty of Education, Sudan University of Science and Technology, Khartoum, Sudan.
²Department of Basic Science, Faculty of Engineering Science, Omdurman Islamic University, Khartoum, Sudan.
³Department of Chemistry, Faculty of Science, Sudan University of Science and Technology, Omdurman, Sudan.

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.

Polarizability, Molar Volume, Lipophilicity, Anthrapyrazoles, Murine

Hashim, H. , El-Fakii, M. and Saeed, A. (2020) Activity Trends in Desoxy Anthrapyrazoles: The Influence of Molar Volume, Polarizability and Lipophilicity of N₂ C₅ Side Chains on Their Anticancer Response. Computational Chemistry, 8, 17-26. doi: 10.4236/cc.2020.82003.