Abstract
A series of novel coumarin-3-carboxamide derivatives were designed and synthesized to evaluate their biological activities. The compounds showed little to no activity against gram-positive and gram-negative bacteria but specifically showed potential to inhibit the growth of cancer cells. In particular, among the tested compounds, 4-fluoro and 2,5-difluoro benzamide derivatives (14b and 14e, respectively) were found to be the most potent derivatives against HepG2 cancer cell lines (IC50 = 2.62–4.85 μM) and HeLa cancer cell lines (IC50 = 0.39–0.75 μM). The activities of these two compounds were comparable to that of the positive control doxorubicin; especially, 4-flurobenzamide derivative (14b) exhibited low cytotoxic activity against LLC-MK2 normal cell lines, with IC50 more than 100 μM. The molecular docking study of the synthesized compounds revealed the binding to the active site of the CK2 enzyme, indicating that the presence of the benzamide functionality is an important feature for anticancer activity.
Highlights
Coumarin is one of the potent secondary metabolites in plants [1,2] and fungi [3], and it is characterized by several pharmacological properties [4]
The preparation of pyranocoumarin-3-carboxamide was applied from the previous synthetic strategies reported by Faulgues and colleagues [18] and was described in Scheme 1
The results show that only compounds 10 and 13 exhibited moderate antibacterial activities against gram-positive bacteria, while the other tested compounds displayed minimum inhibitory concentration (MIC) values of more than 128 μg/mL
Summary
Coumarin is one of the potent secondary metabolites in plants [1,2] and fungi [3], and it is characterized by several pharmacological properties [4]. The dehydrated derivative of decursinol, xanthyletin 3, has been shown to possess several biological properties, such as anti-tumor and antibacterial activities [6]. The synthetic N-phenyl coumarin carboxamide 4a has been designed and shown to possess high antibacterial activity against Helicobacter pylori (H. pylori), with the minimum inhibitory concentration (MIC) = 1 μg/mL [15], while the benzyl substitution of coumarin carboxamides 4b–d has been shown to arrest breast cancer cell (BT474 and SKBR-3) growth by inhibiting ErbB-2 and ERK1 MAP kinase. We designed novel pyranocoumarin-3-carboxamide derivatives with the expectation that the carboxamide part could possess active pharmacological properties 4a–d and that the pyran ring moiety could show specific biological proteins, as in the case of xanthyletin
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