Singh, Ankit Kumar; Kumar, Adarsh; Kraljić, Kristina; Pathak, Prateek; Verma, Amita; Novak, Jurica; Kumar, Pradeep (2025) Thioxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids as potential BRAFV600E inhibitors: experimental, computational and biological evaluations. Journal of Molecular Structure, 1349 (Part 1). ISSN 1872-8014
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Abstract
The BRAFV600E mutation is the most common alteration in the BRAF gene, accounting for about 90 of all BRAF mutations, and is frequently observed in melanoma, thyroid cancer, colorectal cancer and several other malignancies. A series of thioxo-tetrahydro-pyrimidine-benzenesulfonamide compounds (P01–P16) was designed to target the αC-OUT/DFG-IN conformation of BRAFV600E, similar to second-generation FDA-approved inhibitors. Molecular docking and dynamics simulations were performed using sorafenib as the reference, followed by biological evaluation. All compounds were tested for anti-proliferative activity in four cancer cell lines and for BRAFV600E kinase inhibition potential. The most potent antiproliferative effects were seen with P09 (MCF-7), P13 (HePG2, TPC-1), and P02 (A375), while P14 showed the highest kinase inhibition, surpassing sorafenib. A structure–activity relationship (SAR) study indicated that electron-withdrawing groups enhanced potency against cell lines as well as in enzyme inhibitory assay.
| Item Type: | Article | ||||||||
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| Uncontrolled Keywords: | BRAF; Thioxo; Pyrimidine-Benzenesulfonamide; Molecular dynamics and anticancer | ||||||||
| Subjects: | NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Chemistry > Physical Chemistry NATURAL SCIENCES > Chemistry > Theoretical Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry BIOTECHNICAL SCIENCES |
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| Divisions: | Center for Informatics and Computing | ||||||||
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| Depositing User: | Jurica Novak | ||||||||
| Date Deposited: | 02 Sep 2025 06:44 | ||||||||
| URI: | http://fulir.irb.hr/id/eprint/9938 | ||||||||
| DOI: | 10.1016/j.molstruc.2025.143620 |
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