Validation of Quantitative Structure-Activity Relationship (QSAR) Model for Photosensitizer Activity Prediction

International Journal of Molecular Sciences

Neni Frimayanti³  Mun Li Yam²  Hong Boon Lee²  Rozana Othman¹  Sharifuddin M. Zain³ 

[1] Drug Design and Development Research Group, University of Malaya, Lembah Pantai 50603, Kuala Lumpur, Malaysia;Drug Discovery Group, Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Selangor Darul Ehsan 47500, Malaysia; E-Mails:;Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai 50603, Kuala Lumpur, Malaysia; E-Mails:

关键词: QSAR;    photodynamic therapy;    photosensitizer;    porphyrin;    IC₅₀ half maximal inhibitory concentration;   

DOI  :  10.3390/ijms12128626

来源: mdpi

【 摘 要 】

Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r² value, r² (CV) value and r² prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC₅₀ values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r² prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.