Synthesis and evaluation of nicotinamide derivative as anti-angiogenic agents |
| |
Authors: | Hye-Eun Choi Jung-Hye Choi Jae Yeol Lee Je Hak Kim Ji Han Kim Joon Kwang Lee Gyu Il Kim Yong Park Yong Ha Chi Soo Heui Paik Joo Han Lee Kyung-Tae Lee |
| |
Institution: | 1. Department of Pharmaceutical Biochemistry, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;2. Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;3. Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;4. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea;5. Central Research Institute, Boryung Pharm. Co. Ltd, 1122-3, Shingil-Dong, Danwon-Gu, Ansan-Si, Kyungki-Do 425-839, Republic of Korea |
| |
Abstract: | Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells. During our continuous efforts to identify more potent anti-angiogenic agents, we synthesized various nicotinamide derivatives and evaluated their anti-angiogenic effects. We found that 2-{1-1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl) pyridine-3-carboxamide (BRN-250) significantly inhibited human umbilical vascular endothelial cells (HUVECs) proliferation, migration, tube formation, and microvessel growth in a concentration range of 10–100 nM. Furthermore, BRN-250 inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway. Taken together, these findings suggest that BRN-250 be considered a potential lead compound for cancer therapy. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|