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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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022424000884 |
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| author | Rahul D. Jawarkar Magdi E.A. Zaki Sami A. Al-Hussain Abdullah Yahya Abdullah Alzahrani Long Chiau Ming Abdul Samad Rahul G. Ingle Suraj N. Mali |
| author_facet | Rahul D. Jawarkar Magdi E.A. Zaki Sami A. Al-Hussain Abdullah Yahya Abdullah Alzahrani Long Chiau Ming Abdul Samad Rahul G. Ingle Suraj N. Mali |
| author_sort | Rahul D. Jawarkar |
| collection | DOAJ |
| description | 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., R2 =0.9259–0.9280, Q2Loo= 0.8579–0.8558, Q2LMO= 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. |
| first_indexed | 2024-03-07T22:53:09Z |
| format | Article |
| id | doaj.art-3ca40588721f47c998ac1efe5db145bc |
| institution | Directory Open Access Journal |
| issn | 2667-0224 |
| language | English |
| last_indexed | 2024-03-07T22:53:09Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj.art-3ca40588721f47c998ac1efe5db145bc2024-02-23T05:00:57ZengElsevierChemical Physics Impact2667-02242024-06-018100544QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitorsRahul D. Jawarkar0Magdi E.A. Zaki1Sami A. Al-Hussain2Abdullah Yahya Abdullah Alzahrani3Long Chiau Ming4Abdul Samad5Rahul G. Ingle6Suraj N. Mali7Department of Medicinal Chemistry, Dr. Rajendra Gode Institute of Pharmacy, University-Mardi Road, Amravati, India; Corresponding authors.Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; Corresponding authors.Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi ArabiaDepartment of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi ArabiaSchool of Medical and Life Sciences, Sunway University, Sunway City, MalaysiaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil, IraqDatta Meghe College of Pharmacy, DMIHER Deemed University, Wardha, IndiaDepartment of Pharmaceutical Chemistry, School of Pharmacy, D.Y. Patil University (Deemed to be University), Sector 7, Nerul, Navi Mumbai 400706, India; Corresponding authors.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., R2 =0.9259–0.9280, Q2Loo= 0.8579–0.8558, Q2LMO= 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.http://www.sciencedirect.com/science/article/pii/S2667022424000884Urokinase-type plasminogen activator inhibitorsQSARPharmacophoric features |
| spellingShingle | Rahul D. Jawarkar Magdi E.A. Zaki Sami A. Al-Hussain Abdullah Yahya Abdullah Alzahrani Long Chiau Ming Abdul Samad Rahul G. Ingle Suraj N. Mali QSAR modelling to predict structural features of certain sulfonamide as Urokinase-type Plasminogen Activator inhibitors Chemical Physics Impact Urokinase-type plasminogen activator inhibitors QSAR Pharmacophoric features |
| title | 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_short | 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 |
| topic | Urokinase-type plasminogen activator inhibitors QSAR Pharmacophoric features |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424000884 |
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