Multiple quantitative structure-activity relationships (QSARs) analysis for orally active trypanocidal N-myristoyltransferase inhibitors

摘要

In the present work, OECD guidelines have been followed for developing QSAR (Quantitative Structure-Activity Relationship) models for anti-HAT (Human African trypanosomiasis) activity of two hundred and seventy pyrazole sulphonamides. The newly developed easily interpretable multiple QSAR models have been successful in identification of many privileged as well as under-privileged molecular descriptors, which could be highly useful for future use of these models by expert and non-experts of QSAR. The multiple QSAR models satisfy threshold values for many statistical parameters such as R-2 = 0.80-0.83, Q(2) = 0.79-0.81, CCCext = 0.82-0.84, etc. thereby assuring good external predictive ability of the models. The multiple QSAR and pharmacophoric models successfully identified that N,4-disubstituted-benze-nesulfonamide moiety, frequency of occurrence of H-bond acceptor from Oxygen atom within nine bonds and some other pharmacophoric features that govern the anti-HAT activity of pyrazole sulphonamides. The results could be very useful to synthetic/medicinal chemists for future modifications of pyrazole sulphonamides as drug candidates. (C) 2018 Elsevier B.V. All rights reserved.