Exploration of the Biological Functions of Bicyclic Pyrazoline Analogue, HJL-A-58A, In Vitro

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题名:	Exploration of the Biological Functions of Bicyclic Pyrazoline Analogue, HJL-A-58A, In Vitro
作者:	潘思妘;Pan, Ssu-Yun
贡献者:	化學學系
关键词:	血管新生;angiogenesis
日期:	2024-08-20
上传时间:	2024-10-09 15:26:43 (UTC+8)
出版者:	國立中央大學
摘要:	薑黃素是香料薑黃中的黃色色素，由於其抗增殖和抗血管生成特性而成為有前途的抗癌劑。然而，薑黃素在體內的生物利用度和功效較低，阻礙了其臨床發展。因此，我們研究了源自單羰基薑黃素類似物的雙雜環衍生物作為潛在的抗癌藥物候選者。我們的研究發現化合物HJL-A-58A是一種新型雙環吡唑啉類似物，它在MDA-MB-231、BT549、MIA PaCa-2、PANC-1和PC-3等癌細胞系中表現出抗增殖活性。此外，化合物HJL-A-58A在這五種癌細胞系中也顯示出抗遷移能力。在細胞週期實驗中，MIA PaCa-2細胞在處理化合物HJL-A-58A 48小時後，呈現劑量依賴性的S期停滯。此外，我們的研究結果表明，化合物HJL-A-58A在管形成測定及離體小鼠主動脈環實驗中皆顯示出有效的血管增生抑制活性，突顯了其在靶向腫瘤脈管系統方面的潛力。這些結果強調了HJL-A-58A透過針對細胞存活、遷移和血管生成途徑來對抗癌症進展的治療潛力。;Curcumin, the yellow pigment in the spice turmeric, has emerged as a promising anti-cancer agent due to its anti-proliferative and anti-angiogenic properties. However, curcumin′s low bioavailability and efficacy in vivo have hindered its clinical development. Therefore, we investigated bis-heterocyclic derivatives derived from monocarbonyl curcumin analogs as potential anti-cancer drug candidates. Our study found that compound HJL-A-58A, a novel bicyclic pyrazoline analog, exhibited anti-proliferative activity in cancer cell lines such as MDA-MB-231, BT549, MIA PaCa-2, PANC-1, and PC-3. Additionally, compound HJL-A-58A demonstrated anti-migratory capabilities in these five cancer cell lines. In cell cycle experiments, MIA PaCa-2 cells were arrested in the S phase in a dose-dependent manner after treatment with compound HJL-A-58A for 48 hours. Furthermore, our results indicate that compound HJL-A-58A shows effective angiogenesis inhibitory activity in tube formation assays and in ex vivo mice aortic ring assays, highlighting its potential in targeting tumor vasculature. These results underscore the therapeutic potential of HJL-A-58A in combating cancer progression through targeting cell survival, migration, and angiogenesis pathways.
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