Mizuta Satoshi, Mosaddeque Farhana, Tun Mya Myat Ngwe, Teklemichael Awet Alem, Taniguchi Mayumi, Hosokawa Masashi, Yamaguchi Tomoko, Makau Juliann, Huy Nguyen Tien, Mizukami Shusaku, Nishida Noriyuki, Morita Kouichi, Hirayama Kenji
Center for Bioinformatics and Molecular Medicine, Nagasaki University, 1-14 Bunkyo, 852-8521, Nagasaki, Japan.
Department of Immunogenetics Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan.
ChemMedChem. 2023 Apr 3;18(7):e202200586. doi: 10.1002/cmdc.202200586. Epub 2023 Feb 8.
We report the structural functionalization of the terminal amino group of N -(7-chloroquinolin-4-yl) butane-1,4-diamine, leading to a series of 7-chloro-4-aminoquinoline derivatives, and their evaluation as potent anti-malarial and anti-viral agents. Some compounds exhibited promising anti-malarial effects against the Plasmodium falciparum 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains. In addition, these compounds were assayed in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5 h, bearing an N-mesityl thiourea group, displayed pronounced anti-infectious effects against malaria, IAV, and SARS-CoV-2. These results provide new insights into drug discovery for the prevention or treatment of malaria and virus co-infection.
我们报道了N-(7-氯喹啉-4-基)丁烷-1,4-二胺末端氨基的结构功能化，从而得到了一系列7-氯-4-氨基喹啉衍生物，并对其作为强效抗疟疾和抗病毒药物进行了评估。一些化合物对恶性疟原虫3D7（氯喹敏感）和Dd2（氯喹耐药）菌株表现出有前景的抗疟疾效果。此外，这些化合物还针对甲型流感病毒（IAV）和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进行了体外检测。带有N-均三甲苯基硫脲基团的化合物5h对疟疾、IAV和SARS-CoV-2显示出显著的抗感染效果。这些结果为预防或治疗疟疾和病毒合并感染的药物发现提供了新的见解。
