Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4
In the present study, we aim to identify a potential drug candidate that targets the Monocarboxylate Transporter-4 (MCT-4) protein. Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4. We screened 2,11,192 potential leads through ZINC database, which were atleast 5...
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Elsevier
2025-06-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750025000204 |
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| author | Asma Khatoon Zaidi Anurag Kumar Rohit Kumar Jyoti Singh Sneha Yadav Archana Bharti Sonkar Dharmendra Kumar Neeraj Kumar Shrivastava Mohd Nazam Ansari Abdulaziz S. Saeedan Gaurav Kaithwas |
| author_facet | Asma Khatoon Zaidi Anurag Kumar Rohit Kumar Jyoti Singh Sneha Yadav Archana Bharti Sonkar Dharmendra Kumar Neeraj Kumar Shrivastava Mohd Nazam Ansari Abdulaziz S. Saeedan Gaurav Kaithwas |
| author_sort | Asma Khatoon Zaidi |
| collection | DOAJ |
| description | In the present study, we aim to identify a potential drug candidate that targets the Monocarboxylate Transporter-4 (MCT-4) protein. Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4. We screened 2,11,192 potential leads through ZINC database, which were atleast 50 % structurally similar with SYR. After in-depth analysis, 900 molecules were shortlisted based on Lipinski's rule, optimal molecular weight, binding energy, hydrogen bonding, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties that render them viable MCT-4 inhibitors. The outcome underscored Brucine (BRU) as the most promising lead molecule within a cohort of ten potential compounds. BRU is a monoterpenoid indole alkaloid and is used in the regulation of high blood pressure and other comparatively benign cardiac ailments. As such, no reports is available emphasizing the efficacy of BRU on lactate transport or mammary gland carcinoma. BRU demonstrated strong affinity for the MCT-4 transporter's catalytic domain, forming significant hydrophobic and polar interactions with essential amino acids at the binding site. BRU demonstrated significant cytotoxicity and increased the extracellular lactate levels in MCF-7 cells. The findings strongly encouraged BRU's effectiveness, offering promising paths for subsequent investigations. |
| format | Article |
| id | doaj-art-34ff2bbc4a7844b090ca0717a14d4145 |
| institution | Kabale University |
| issn | 2214-7500 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj-art-34ff2bbc4a7844b090ca0717a14d41452025-01-19T06:25:04ZengElsevierToxicology Reports2214-75002025-06-0114101902Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4Asma Khatoon Zaidi0Anurag Kumar1Rohit Kumar2Jyoti Singh3Sneha Yadav4Archana Bharti Sonkar5Dharmendra Kumar6Neeraj Kumar Shrivastava7Mohd Nazam Ansari8Abdulaziz S. Saeedan9Gaurav Kaithwas10Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi ArabiaDepartment of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India; Corresponding author.In the present study, we aim to identify a potential drug candidate that targets the Monocarboxylate Transporter-4 (MCT-4) protein. Syrosingopine (SRY) is a well-established inhibitor of lactate transport through MCT-4. We screened 2,11,192 potential leads through ZINC database, which were atleast 50 % structurally similar with SYR. After in-depth analysis, 900 molecules were shortlisted based on Lipinski's rule, optimal molecular weight, binding energy, hydrogen bonding, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties that render them viable MCT-4 inhibitors. The outcome underscored Brucine (BRU) as the most promising lead molecule within a cohort of ten potential compounds. BRU is a monoterpenoid indole alkaloid and is used in the regulation of high blood pressure and other comparatively benign cardiac ailments. As such, no reports is available emphasizing the efficacy of BRU on lactate transport or mammary gland carcinoma. BRU demonstrated strong affinity for the MCT-4 transporter's catalytic domain, forming significant hydrophobic and polar interactions with essential amino acids at the binding site. BRU demonstrated significant cytotoxicity and increased the extracellular lactate levels in MCF-7 cells. The findings strongly encouraged BRU's effectiveness, offering promising paths for subsequent investigations.http://www.sciencedirect.com/science/article/pii/S2214750025000204Monocarboxylate Transporter-4SyrosingopineBrucineBreast cancerLactate |
| spellingShingle | Asma Khatoon Zaidi Anurag Kumar Rohit Kumar Jyoti Singh Sneha Yadav Archana Bharti Sonkar Dharmendra Kumar Neeraj Kumar Shrivastava Mohd Nazam Ansari Abdulaziz S. Saeedan Gaurav Kaithwas Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 Toxicology Reports Monocarboxylate Transporter-4 Syrosingopine Brucine Breast cancer Lactate |
| title | Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 |
| title_full | Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 |
| title_fullStr | Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 |
| title_full_unstemmed | Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 |
| title_short | Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4 |
| title_sort | repurposing brucine as a chemopreventive agent in mammary gland carcinoma regulating lactate transport through mct 4 |
| topic | Monocarboxylate Transporter-4 Syrosingopine Brucine Breast cancer Lactate |
| url | http://www.sciencedirect.com/science/article/pii/S2214750025000204 |
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