QSAR Investigation on 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carbothioamides as EGFR Kinase Inhibitors

 

In order to establish a quantitative relationship between epidermal growth factor receptor (EGFR) kinase inhibitory activity and physicochemical / structural properties, a quantitative structure activity relationship (QSAR) study was performed on a series of 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carbothioamides. Using multiple linear regression (MLR) analysis, many statistical regression equations were developed. Model 2 justifies 72 percent (r2 = 0.7194) of the total variance in the training set and possesses internal (q2) and external (pred r2) predictive ability of 65 percent (q2 = 0.6472) and 75 percent (pred r2 = 0.7530) respectively. This model was further evaluated, and using Mean Absolute Error (MAE)-based criteria on 95 percent of the data, MAE+3* Standard Deviation (SD)[= 0.3359 (0.25 * TrainingSetRange = 0.55250)] revealed that the model’s projection quality is good. T C C 4 has a positive coefficient value in this model. [In a molecule, this is the number of carbon atoms separated by 4 bond distance from any carbon atom (single, double, or triple bonded)] and Most+ve&-ve Potentail Distance The biological activity of [this descriptor denotes the distance between points with the highest value of +ve and highest value of –ve electrostatic potential on the van der waals surface area of the molecule] revealed that a higher value leads to increased epidermal growth factor receptor (EGFR) kinase inhibitory activity, while a lower value leads to decreased activity. The descriptors T C C 4 and Most+ve&-ve Potentail Distance contribute 75.97 percent and 24.03 percent, respectively, according to the contribution chart.

Author(s) Details:

Sanmati K. Jain,
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh-495009, India

Sanjay K. Lanjhiyana,
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh-495009, India.

Ajay Gupta,
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh-495009, India.

B. G. V. S. Jagan,
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh-495009, India.

Sunil Sahu,
Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh-495009, India.

Please see the link here: https://stm.bookpi.org/CAPR-V2/article/view/6577

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