Synthesis and Cytotoxicity of Thieno[2,3-b]Pyridine Derivatives Toward Sensitive and Multidrug-Resistant Leukemia Cells

• Main Authors: Salah A. Al-Trawneh, Amer H. Tarawneh, Anastassiya V. Gadetskaya, Ean-Jeong Seo, Mohammad R. Al-Ta’ani, Samir A. Al-Taweel, Mustafa M. El-Abadelah
• Format: Article
• Language: English
• Published: Slovenian Chemical Society 2021-06-01
• Series: Acta Chimica Slovenica
• Subjects: thieno[2,3-b]pyridine; multidrug resistance; cytotoxicity.
• Online Access: https://journals.matheo.si/index.php/ACSi/article/view/6609
• ISSN: 1318-0207; 1580-3155

A new series of substituted ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e were prepared by utilizing ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (1) and replacing of the 2-chlorine with anions obtained from phenol (2a), salicylaldehyde derivatives 2b–d or thiophenol (2e), leading to the respective ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a–e. The new compounds were evaluated for their in vitro cytotoxicity towards sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. The screening revealed that compounds 3a, 3b, and 3e inhibited the growth of both cell lines. Compound 3b, with a phenol moiety, exhibited the highest growth inhibitory activity against CEM/ADR5000 and CCRF-CEM cells with IC50 values 4.486 ± 0.286 and 2.580 ± 0.550 µM, respectively. Collectively, the presented results demonstrate that the synthesized thieno[2,3-b]pyridines warrant further exploration for potential use as anti-cancer agents.