Advances in Non‐operative Therapy in Pancreatic Cancer

The cytotoxicity of 19 N-aryl-substituted hydroxamic acids has been tested in vitro towards human breast cancer MCF -7 cell lines by MTT assay. The IC 50 values were found to be in the range from 61.94 to 337.54 mM. A total of 18 out of 19 molecules had higher inhibitory activities than hydroxyurea against MCF -7 cell. Five compounds with IC 50 values in micromolar range were 3-to 5-folds more potent than hydroxyurea (IC 50 ¼ 307.15 mM). By partial least squares (PLS) regression, 2D-QSAR model reported herein provide interesting insight in understanding hydrophobic, electronic, and structural requirements of antitumor activity among these set of the compounds. The cross-validated Q 2 cum values for optimal PLS model of hydroxamic acids is above 0.638 (remarkably higher 0.50), indicating good predictive abilities for log 1/IC 50 values of hydroxamic acids (HAs). The k-nearest neighbor molecular field analysis (kNN-MFA) approach was used to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models for these sets of molecules. Statistically stepwise variable selection k-nearest neighbor molecular field analysis (SW-kNN-MFA) model is comparatively better as compared to the other two (i.e. simulated annealing k-nearest neighbor molecular field analysis, SA-kNN-MFA, and genetic algorithm k-nearest neighbor molecular field analysis, GA-kNN-MFA) with respect to both the internal (q 2 ¼ 0.7461) as well as external (pred_r 2 ¼ 0.6107) model validation and correctly predicts activity of ca. 74.61% and ca. 61.07% for the training and test set, respectively. It uses one steric and one electrostatic fields along with its 3k nearest neighbor (k ¼ 3) to evaluate the activity of new molecules. The developed SW-kNN-MFA model field plot indicated that the positive steric and electric potential are favorable for the increase in the activity and hence more bulky substituent at 5-position of phenyl ring connected at amide group and less electronegative substituent at 3-position of phenyl ring connected to carboxyl group are favourable for the increase in the potency of the molecules.

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The Chemistry of Hydroxamic Acids

Gupta¹,

Sharma²

2013

Hydroxamic Acids

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Advances in Non‐operative Therapy in Pancreatic Cancer

Cited by 11 publications

References 72 publications

Hydroxamic Acids − An Intriguing Family of Enzyme Inhibitors and Biomedical Ligands

Hydroxamic Acids − An Intriguing Family of Enzyme Inhibitors and Biomedical Ligands

Hydroxamic Acids Analogous Against Breast Cancer Cells: 2D‐QSAR and 3D‐QSAR Studies

The Chemistry of Hydroxamic Acids

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