Kumar Kewal, Pradines Bruno, Madamet Marilyn, Amalvict Rémy, Kumar Vipan
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
Unité de Parasitologie et d'Entomologie, Département de Microbiologie, Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France; Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, Inserm 1095, Marseille, France; Centre National de Référence du Paludisme, Marseille, France.
Eur J Med Chem. 2014 Oct 30;86:113-21. doi: 10.1016/j.ejmech.2014.08.053. Epub 2014 Aug 16.
A series of ferrocenylchalcone-β-lactam conjugates were synthesized and evaluated against 3D7 (CQ-Sensitive) and W2 (CQ-Resistant) strains of Plasmodium falciparum. The SAR studies revealed the dependence of activities at N-1 substituent of β-lactam ring with compounds being more potent on resistant strain. The compound 9f and 9l with N-cyclohexyl substituent proved to be the most potent and non-cytotoxic among the series exhibiting IC50 values of 2.36 and 2.43 μM respectively, against W2 strain of P. falciparum.
合成了一系列二茂铁基查尔酮-β-内酰胺缀合物，并针对恶性疟原虫的3D7（对氯喹敏感）和W2（对氯喹耐药）菌株进行了评估。构效关系研究表明，β-内酰胺环N-1取代基的活性具有依赖性，化合物对耐药菌株的活性更强。在该系列化合物中，具有N-环己基取代基的化合物9f和9l被证明是最有效的且无细胞毒性，对恶性疟原虫W2菌株的IC50值分别为2.36和2.43 μM。
