QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors
The serine hydrolase family includes serine proteases. It is essential for hydrolyzing protein peptide bonds and breaking them. The urokinase-type plasminogen activator (uPA) selectively binds to the uPAR on numerous cell types, including cancer cells. Pericellular proteolysis of cell-bound proteins...
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my.sunway.eprints.26112024-05-16T01:10:25Z http://eprints.sunway.edu.my/2611/ QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors Jawarkar, Rahul D Zaki, Magdi E A Al-Hussain, Sami Alzahrani, Abdullah Yahya Abdullah Long, Chiau Ming * Samad, Abdul Ingle, Rahul G. Mali, Suraj N. QP Physiology RM Therapeutics. Pharmacology The serine hydrolase family includes serine proteases. It is essential for hydrolyzing protein peptide bonds and breaking them. The urokinase-type plasminogen activator (uPA) selectively binds to the uPAR on numerous cell types, including cancer cells. Pericellular proteolysis of cell-bound proteins requires this interaction. High uPA and uPAR levels regularly worsen cancer prognoses. Thus, small chemical active-site inhibitors that block uPA may diminish cancer cell invasion and metastasis. In compliance with Organization for Economic Corporation and Development guidelines, this research performed a complete Quantitative structure activity relationship analysis of sulfonamide compounds as Urokinase-type Plasminogen Activator inhibitors. Py-Descriptors were used for this investigation. PyDescriptor uses PyMOL standards and idioms to calculate 11,145 simple molecular descriptors. This plugin calculates molecular descriptors irrespective of molecular representation properties like atom numbering or labelling, spatial reference frame, translational and rotational invariance, etc. The investigation sought to find essential and hidden structural characteristics that regulate sulfonamide-type drugs’ Urokinase-type Plasminogen Activator Inhibitory action. Twenty-eight sulfonamide chemicals are used in the Quantitative structure activity relationship study to generate statistically robust and highly predictive univariate and multivariate models. All models were thoroughly evaluated and meet several statistical parameter thresholds (e.g., R 2 =0.9259–0.9280, Q 2 Loo =0.8579–0.8558, Q 2 LMO =0.8013–0.7865). The analysis reveal that occurance of ring carbon atoms exactly at 3 A0 from carbon atom, number of negatively charged atoms from sulphur atoms within 5 bonds, presence of hydrogen atom exactly at 3 bonds from donar atoms, presence of carbon atom exactly at 4 A0 from donar atom, presence of acceptor atom exactly at 5 A0 from sulphur atom and sum of partial charges of lipo atoms within 6 bonds from sulphur atom are important pharmacophoric features for Urokinase- type Plasminogen Activator Inhibition binding affinity. Thus, the developed Quantitative structure activity relationship study has an equilibrium of quantitative and qualitative tactics. The results could be useful for future optimizations of sulfonamide analogues. Elsevier 2024 Article PeerReviewed Jawarkar, Rahul D and Zaki, Magdi E A and Al-Hussain, Sami and Alzahrani, Abdullah Yahya Abdullah and Long, Chiau Ming * and Samad, Abdul and Ingle, Rahul G. and Mali, Suraj N. (2024) QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors. Chemical Physics Impact, 8. ISSN 2667-0224 https://doi.org/10.1016/j.chphi.2024.100544 10.1016/j.chphi.2024.100544 |
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QP Physiology RM Therapeutics. Pharmacology Jawarkar, Rahul D Zaki, Magdi E A Al-Hussain, Sami Alzahrani, Abdullah Yahya Abdullah Long, Chiau Ming * Samad, Abdul Ingle, Rahul G. Mali, Suraj N. QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
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The serine hydrolase family includes serine proteases. It is essential for hydrolyzing protein peptide bonds and breaking them. The urokinase-type plasminogen activator (uPA) selectively binds to the uPAR on numerous cell types, including cancer cells. Pericellular proteolysis of cell-bound proteins requires this interaction. High uPA and uPAR levels regularly worsen cancer prognoses. Thus, small chemical active-site inhibitors that block uPA may diminish cancer cell invasion and metastasis. In compliance with Organization for Economic Corporation and Development guidelines, this research performed a complete Quantitative structure activity relationship analysis of sulfonamide compounds as Urokinase-type Plasminogen Activator inhibitors. Py-Descriptors were used for this investigation. PyDescriptor uses PyMOL standards and idioms to calculate 11,145 simple molecular descriptors. This plugin calculates molecular descriptors irrespective of molecular representation properties like atom numbering or labelling, spatial reference frame, translational and rotational invariance, etc. The investigation sought to find essential and hidden structural characteristics that regulate sulfonamide-type drugs’ Urokinase-type Plasminogen Activator Inhibitory action. Twenty-eight sulfonamide chemicals are used in the Quantitative structure activity relationship study to generate statistically robust and highly predictive univariate and multivariate models. All models were thoroughly evaluated and meet several statistical parameter thresholds (e.g., R 2 =0.9259–0.9280, Q 2 Loo =0.8579–0.8558, Q 2 LMO =0.8013–0.7865). The analysis reveal that occurance of ring carbon atoms exactly at 3 A0 from carbon atom, number of negatively charged atoms from sulphur atoms within 5 bonds, presence of hydrogen atom exactly at 3 bonds from donar atoms, presence of carbon atom exactly at 4 A0 from donar atom, presence of acceptor atom exactly at 5 A0 from sulphur atom and sum of partial charges of lipo atoms within 6 bonds from sulphur atom are important pharmacophoric features for Urokinase- type Plasminogen Activator Inhibition binding affinity. Thus, the developed Quantitative structure activity relationship study has an equilibrium of quantitative and qualitative tactics. The results could be useful for future optimizations of sulfonamide analogues. |
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Article |
author |
Jawarkar, Rahul D Zaki, Magdi E A Al-Hussain, Sami Alzahrani, Abdullah Yahya Abdullah Long, Chiau Ming * Samad, Abdul Ingle, Rahul G. Mali, Suraj N. |
author_facet |
Jawarkar, Rahul D Zaki, Magdi E A Al-Hussain, Sami Alzahrani, Abdullah Yahya Abdullah Long, Chiau Ming * Samad, Abdul Ingle, Rahul G. Mali, Suraj N. |
author_sort |
Jawarkar, Rahul D |
title |
QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
title_short |
QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
title_full |
QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
title_fullStr |
QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
title_full_unstemmed |
QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors |
title_sort |
qsar modelling to predict structural features of certain sulfonamide as urokinase-type plasminogen activator inhibitors |
publisher |
Elsevier |
publishDate |
2024 |
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http://eprints.sunway.edu.my/2611/ https://doi.org/10.1016/j.chphi.2024.100544 |
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