Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer
Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this stud...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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MDPI AG,
2023-05-01T00:00:00Z.
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| Summary: | Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds <b>7a</b>, <b>7d</b>, and <b>7f</b> were promising. Among these, <b>7f</b> (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds <b>7a</b>, <b>7d</b> and <b>7f</b> were also tested for their cytotoxic effects on healthy cell line but only compound <b>7d</b> showed selectivity. Compounds <b>7a</b>, <b>7d</b>, and <b>7f</b> showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC<sub>50</sub> value was observed for <b>7c</b> (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds <b>7a</b> (3.78 µM), <b>7c</b> (2.60 µM), <b>7e</b> (3.3 µM), and <b>7f</b> (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds <b>7c</b>, <b>7e</b>, and <b>7f</b> to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, <b>7a</b> and <b>7f</b> were identified as the most promising compounds. |
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| Item Description: | 10.3390/pharmaceutics15051441 1999-4923 |