Conventional QSAR analysis on 2-cyano-4-fluoro-1-thiovalylpyrrolidine analogues as dipeptidyl peptidase-IV inhibitors

Conventional quantitative structure activity relationship (QSAR) analysis was performed on 2-cyano-4-
fluoro-1-thiovalylpyrrolidine analogues for their dipeptidyl peptidase-IV inhibitory activity (DPP-IV
inhibitors) using VlifeQSARPro software. Partial least square (PLS) linear regression analysis coupled
with stepwise variable selection method was applied to derive QSAR models which were further validated
for statistical significance by internal and external validation. Statistically significant QSAR models were
generated. Among them most significant model has squared correlation coefficient (r2), cross validated
correlation coefficient (q2) and predictive correlation coefficient (pred_r2) 0.8369, 0.7206 and 0.8003
respectively. The QSAR model indicates that the descriptors SssScount [total number of sulphur atom
connected with two single bonds], SulfursCount [number of sulphur atoms in a compound] and T_3_C_7
[count of number of triple bonded atoms (i.e. any triple bonded atom, T_3) separated from carbon atom
by 7 bonds in a molecule] contributing (positively) 26.08%, 27.11% and 9.44% respectively to biological
activity. Descriptors T_N_O_6 [count of number of Nitrogen atoms (single, double or triple bonded)
separated from any oxygen atom (single or double bonded) by 6 bond distance in a molecule] and +ve
PotentialSurfaceArea [total van der Waals surface area with positive electrostatic potential of the
molecule] contributing (inversely) 19.86% and 17.51% respectively to biological activity.

Author(s): Sanmati K. Jain, Sarthak Rout and Amita Jaiswal

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