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.