Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches
Pazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results dep...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Analytica |
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| Online Access: | https://www.mdpi.com/2673-4532/3/1/11 |
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| author | Ahmet Cetinkaya Mehmet Gokhan Caglayan Mehmet Altay Unal Pinar Beyazkilic Caglar Elbuken Esen Bellur Atici Sibel A. Ozkan |
| author_facet | Ahmet Cetinkaya Mehmet Gokhan Caglayan Mehmet Altay Unal Pinar Beyazkilic Caglar Elbuken Esen Bellur Atici Sibel A. Ozkan |
| author_sort | Ahmet Cetinkaya |
| collection | DOAJ |
| description | Pazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results depending on the dose. Renal cell carcinoma is the most sensitive carcinoma to pazopanib, with 77% inhibition at the 10 mg/kg dose. Clinical studies have shown 53% to 65% inhibition in carcinomas such as breast carcinoma, prostate carcinoma, and melanoma. Plasma proteins such as human serum albumin (HSA) have a critical role in transporting and storing bioactive components. This feature of HSA is very important for the development of cancer therapy. Here, we investigated the interaction between PAZ and HSA to evaluate their binding strength, binding types, and conformational change in HSA. We used spectroscopic methods to assess the drug–protein interaction. Fluorescence measurements revealed that the interaction of PAZ with HSA occurred via the static quenching mechanism. The calculated binding number and binding constants were 1.041 and 1.436 × 10<sup>6</sup> M<sup>−1</sup>, respectively, at 298.15 K based on fluorescence screening. The high binding constant and calculated Gibbs free energy at different temperatures showed spontaneous and strong binding. Circular dichroism measurements showed that the α-helix structure of HSA was retained as the secondary structure, with a slight reduction in its percentage after adding PAZ. Furthermore, molecular modeling studies suggested that the docking score of PAZ is higher than those of bicalutamide and ibuprofen, the drugs that were chosen as model competitors against PAZ. Accordingly, PAZ was found to replace bicalutamide and ibuprofen on the HSA binding site, which was also confirmed by UV absorption spectroscopy. |
| first_indexed | 2024-03-09T20:12:36Z |
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| id | doaj.art-67cd263b7bc248e1bb6f3b3dfef83812 |
| institution | Directory Open Access Journal |
| issn | 2673-4532 |
| language | English |
| last_indexed | 2024-03-09T20:12:36Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Analytica |
| spelling | doaj.art-67cd263b7bc248e1bb6f3b3dfef838122023-11-24T00:09:18ZengMDPI AGAnalytica2673-45322022-03-013114416010.3390/analytica3010011Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking ApproachesAhmet Cetinkaya0Mehmet Gokhan Caglayan1Mehmet Altay Unal2Pinar Beyazkilic3Caglar Elbuken4Esen Bellur Atici5Sibel A. Ozkan6Faculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara 06560, TurkeyFaculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara 06560, TurkeyStem Cell Institute, Ankara University, Balgat, Ankara 06520, TurkeyUNAM-National Nanotechnology Research Center, Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, TurkeyUNAM-National Nanotechnology Research Center, Institute of Materials Science and Nanotechnology, Bilkent University, Ankara 06800, TurkeyDEVA Holding A.S., R&D Center, Tekirdag 59510, TurkeyFaculty of Pharmacy, Department of Analytical Chemistry, Ankara University, Ankara 06560, TurkeyPazopanib (PAZ), a tyrosine kinase inhibitor, is used to treat advanced renal cell carcinoma (RCC) and advanced soft tissue sarcoma (STS). The FDA approved PAZ for RCC in 2009 and for STS in 2012. The antitumor activity of pazopanib, according to the degree of inhibition, shows different results depending on the dose. Renal cell carcinoma is the most sensitive carcinoma to pazopanib, with 77% inhibition at the 10 mg/kg dose. Clinical studies have shown 53% to 65% inhibition in carcinomas such as breast carcinoma, prostate carcinoma, and melanoma. Plasma proteins such as human serum albumin (HSA) have a critical role in transporting and storing bioactive components. This feature of HSA is very important for the development of cancer therapy. Here, we investigated the interaction between PAZ and HSA to evaluate their binding strength, binding types, and conformational change in HSA. We used spectroscopic methods to assess the drug–protein interaction. Fluorescence measurements revealed that the interaction of PAZ with HSA occurred via the static quenching mechanism. The calculated binding number and binding constants were 1.041 and 1.436 × 10<sup>6</sup> M<sup>−1</sup>, respectively, at 298.15 K based on fluorescence screening. The high binding constant and calculated Gibbs free energy at different temperatures showed spontaneous and strong binding. Circular dichroism measurements showed that the α-helix structure of HSA was retained as the secondary structure, with a slight reduction in its percentage after adding PAZ. Furthermore, molecular modeling studies suggested that the docking score of PAZ is higher than those of bicalutamide and ibuprofen, the drugs that were chosen as model competitors against PAZ. Accordingly, PAZ was found to replace bicalutamide and ibuprofen on the HSA binding site, which was also confirmed by UV absorption spectroscopy.https://www.mdpi.com/2673-4532/3/1/11pazopanibhuman serum albuminfluorescence spectroscopycircular dichroismmolecular docking |
| spellingShingle | Ahmet Cetinkaya Mehmet Gokhan Caglayan Mehmet Altay Unal Pinar Beyazkilic Caglar Elbuken Esen Bellur Atici Sibel A. Ozkan Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches Analytica pazopanib human serum albumin fluorescence spectroscopy circular dichroism molecular docking |
| title | Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches |
| title_full | Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches |
| title_fullStr | Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches |
| title_full_unstemmed | Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches |
| title_short | Investigation of Pazopanib and Human Serum Albumin Interaction Using Spectroscopic and Molecular Docking Approaches |
| title_sort | investigation of pazopanib and human serum albumin interaction using spectroscopic and molecular docking approaches |
| topic | pazopanib human serum albumin fluorescence spectroscopy circular dichroism molecular docking |
| url | https://www.mdpi.com/2673-4532/3/1/11 |
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