Computational Chemistry, 2020, 8, 17-26 https://www.scirp.org/journal/cc ISSN Online: 2332-5984 ISSN Print: 2332-5968 DOI: 10.4236/cc.2020.82003 Mar. 3, 2020 17 Computational Chemistry Activity Trends in Desoxy Anthrapyrazoles: The Influence of Molar Volume, Polarizability and Lipophilicity of N 2 C 5 Side Chains on Their Anticancer Response Howida A. Hashim 1* , Mohamed Osman M. A. El-Fakii 2 , Ahmed Elsadig M. Saeed 3 1 Department of Science, Faculty of Education, Sudan University of Science and Technology, Khartoum, Sudan 2 Department of Basic Science, Faculty of Engineering Science, Omdurman Islamic University, Khartoum, Sudan 3 Department of Chemistry, Faculty of Science, Sudan University of Science and Technology, Omdurman, Sudan Abstract QSAR methodology was used to assess the effects of lipophilicity (logP), mo- lar volume (MV) and polarizability (pl) of the side chains at N 2 and C 5 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/logIC 50 ). The main data set shows poor correla- tions between biological response and the descriptors with exception of MV of the C 5 side chain, where a moderate correlation was discerned ( 2 0.60 P R = , n = 18, two outliers). To extract more information regarding mechanism, the main data set was visually classified to three clusters depending on N 2 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 mis- cellaneous substituents at both N 2 and C 5 . For cluster 1, MV and pl of C 5 show high correlation with biological response (R 2 ’s = 0.75 and 0.72 respec- tively) while logP gives a weak correlation (R 2 = 0.44). For cluster 2, the cor- relations of logP and pl of C 2 side chain are higher ( 2 0.66 P Rs = ′ and 0.62 re- spectively) compared with MV ( 2 0.16 P R = ). Cluster 3 shows very poor corre- lation with all descriptors ( 2 ~ 0.3 P Rs ′ ). This indicates mechanistic distinction between the three clusters. Derived descriptors which represent the difference between the descriptors of N 2 and C 5 side chains where used to explore the presence of interplay between these descriptors in affecting variability of the biological response. How to cite this paper: Hashim, H.A., El-Fakii, M.O.M.A. and Saeed, A.E.M. (2020) Activity Trends in Desoxy Anthra- pyrazoles: The Influence of Molar Volume, Polarizability and Lipophilicity of N 2 C 5 Side Chains on Their Anticancer Response. Computational Chemistry, 8, 17-26. https://doi.org/10.4236/cc.2020.82003 Received: December 18, 2019 Accepted: February 29, 2020 Published: March 3, 2020 Copyright © 2020 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access