Proposal and evaluation of a new norm index-based QSAR model to predict pEC50 and pCC50 activities of HEPT derivatives

doi:10.1016/j.cjche.2016.04.010

Chinese Journal of Chemical Engineering ›› 2016, Vol. 24 ›› Issue (10): 1464-1469.DOI: 10.1016/j.cjche.2016.04.010

• 第25届中国过程控制会议专栏 • 上一篇下一篇

Proposal and evaluation of a new norm index-based QSAR model to predict pEC₅₀ and pCC₅₀ activities of HEPT derivatives

Kanwal Shahid¹, Qiang Wang¹, Qingzhu Jia², Lei Li¹, Xue Cui², Shuqian Xia³, Peisheng Ma³

1 School of Chemical Engineering and Material Science, Tianjin University of Science and Technology, 13 St. TEDA, Tianjin 300457, China;
2 School of Marine and Environment Science, Tianjin University of Science and Technology, 13 St. TEDA, Tianjin 300457, China;
3 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China

收稿日期:2015-11-11 修回日期:2016-03-18 出版日期:2016-10-28 发布日期:2016-11-19
通讯作者: Qiang Wang,E-mail address:wang_q@tust.edu.cn.
基金资助:
Supported by the National Natural Science Foundation of China (21306137).

Proposal and evaluation of a new norm index-based QSAR model to predict pEC₅₀ and pCC₅₀ activities of HEPT derivatives

Kanwal Shahid¹, Qiang Wang¹, Qingzhu Jia², Lei Li¹, Xue Cui², Shuqian Xia³, Peisheng Ma³

1 School of Chemical Engineering and Material Science, Tianjin University of Science and Technology, 13 St. TEDA, Tianjin 300457, China;
2 School of Marine and Environment Science, Tianjin University of Science and Technology, 13 St. TEDA, Tianjin 300457, China;
3 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China

Received:2015-11-11 Revised:2016-03-18 Online:2016-10-28 Published:2016-11-19
Supported by:
Supported by the National Natural Science Foundation of China (21306137).

摘要/Abstract

摘要： The search and development of anti-HIV drugs is currently one of themost urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship (QSAR) model based on some new norm indexes, was obtained to a series ofmore than 150 HEPT derivatives (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine) to find their pEC₅₀ (the required effective concentration to achieve 50% protection ofMT-4 cells against the cytopathic effect of virus) and pCC₅₀ (the required cytotoxic concentration to reduce visibility of 50% mock infected cell) activities. The model efficiencies were then validated using the leave-one-out cross validation (LOO-CV) and yrandomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pEC₅₀ and pCC₅₀ with the higher R_train² and the higher R_test². By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEPT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC₅₀ and pCC₅₀ of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pEC₅₀ and pCC₅₀ of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model might have the potential to be further utilized for other biological activities of HEPT derivatives.

关键词: Mathematical modeling, Structure-activity relationship, Pharmaceuticals, HEPT derivatives, Anti-HIV-1 activity, Prediction

Abstract: The search and development of anti-HIV drugs is currently one of themost urgent tasks of pharmacological studies. In this work, a quantitative structure-activity relationship (QSAR) model based on some new norm indexes, was obtained to a series ofmore than 150 HEPT derivatives (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine) to find their pEC₅₀ (the required effective concentration to achieve 50% protection ofMT-4 cells against the cytopathic effect of virus) and pCC₅₀ (the required cytotoxic concentration to reduce visibility of 50% mock infected cell) activities. The model efficiencies were then validated using the leave-one-out cross validation (LOO-CV) and yrandomization test. Results indicated that this new model was efficient and could provide satisfactory results for prediction of pEC₅₀ and pCC₅₀ with the higher R_train² and the higher R_test². By using the leverage approach, the applicability domain of this model was further investigated and no response outlier was detected for HEPT derivatives involved in this work. Comparison results with reference methods demonstrated that this new method could result in significant improvements for predicting pEC₅₀ and pCC₅₀ of anti-HIV HEPT derivatives. Moreover, results shown in this present study suggested that these two absolutely different activities pEC₅₀ and pCC₅₀ of anti-HIV HEPT derivatives could be predicted well with a totally similar QSAR model, which indicated that this model might have the potential to be further utilized for other biological activities of HEPT derivatives.

Key words: Mathematical modeling, Structure-activity relationship, Pharmaceuticals, HEPT derivatives, Anti-HIV-1 activity, Prediction

Kanwal Shahid, Qiang Wang, Qingzhu Jia, Lei Li, Xue Cui, Shuqian Xia, Peisheng Ma. Proposal and evaluation of a new norm index-based QSAR model to predict pEC₅₀ and pCC₅₀ activities of HEPT derivatives[J]. Chinese Journal of Chemical Engineering, 2016, 24(10): 1464-1469.

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Proposal and evaluation of a new norm index-based QSAR model to predict pEC₅₀ and pCC₅₀ activities of HEPT derivatives

Proposal and evaluation of a new norm index-based QSAR model to predict pEC₅₀ and pCC₅₀ activities of HEPT derivatives

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