Details

Autor(en) / Beteiligte

• Coskun, Goknil Pelin
• Ozhan, Yagmur
• Dobričić, Vladimir
• Bošković, Jelena
• Reis, Rengin
• Sipahi, Hande
• Sahin, Zafer
• Demirayak, Seref

Titel

Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer

Ist Teil von

• Pharmaceutics, 2023-05, Vol.15 (5), p.1441

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 , , and were promising. Among these, (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds , and were also tested for their cytotoxic effects on healthy cell line but only compound showed selectivity. Compounds , , and 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 value was observed for (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds (3.78 µM), (2.60 µM), (3.3 µM), and (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds , , and 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, and were identified as the most promising compounds.