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Current Chemical Biology


ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Research Article

Investigating Structural Requirements of Some Pyrimidine-linked Benzimidazole Derivatives as Anticancer Agents Against MCF-7 Cancerous Cell Line Through the use of 2D and 3D QSARs

Author(s): Kale Mayura*, Khan Sharuk and Hature Jyoti

Volume 13 , Issue 3 , 2019

Page: [232 - 249] Pages: 18

DOI: 10.2174/2212796813666190207144407

Price: $65


Background: Cancer is an extremely fast, unrestrained and pathological propagation of cells. Yet there is no cancer treatment that is 100% efficient against scattered cancer. Heterocycles have been considered as a boon to treat several cancers of which pyrimidine is a core nucleus and holds an important place in cancer chemotherapy which is reflected in the use of drugs such as 5-fluorouracil, erlotinib, gefitinib and caneratinib. Also, many good antitumor active agents possess benzimidazoleas its core nucleus.

Objective: To design novel pyrimidine-linked benzimidazoles and to explore their structural requirements related to anticancer potential.

Methods: 2D and 3D Quantitative structure–activity relationship (QSAR) studies were carried out on a series of already synthesized 27 pyrimidine-benzimidazole derivatives.

Results: Statistically significant and optimum 2D-QSAR model was developed by using step-wise variable multiple linear regression method, yielding correlation coefficient r2 = 0.89, cross-validated squared correlation coefficient q2 = 0.79 and external predictive ability of pred_r2 = 0.73 Best 3D-QSAR model was developed by employing molecular field analysis using step-wise variable k-nearest neighbor method which showed good correlative and predictive abilities in terms of q2 =0.77 and pred_r2= 0.93.

Conclusion: These 2D and 3D models were found to give dependable indications which helped to optimize the pyrimidine-benzimidazole derivatives of the data set. The data yielded by 2D- QSAR and 3D-QSAR models will aid in giving better perceptions about structural requirements for developing newer anticancer agents.

Keywords: MCF-7, 2D-QSAR, 3D-QSAR, MLR, kNN-MFA, anticancer activity.

Graphical Abstract
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