Central Drug Research Institute Chattar Manzil, Mahatma Gandhi Marg, Lucknow, India.
Bioorg Med Chem. 2010 Dec 1;18(23):8289-301. doi: 10.1016/j.bmc.2010.09.071. Epub 2010 Oct 14.
A series of 4-alkylaminoaryl phenyl cyclopropyl methanones (6a-6u and 8a-8c) were synthesized from 4-fluorochalcones (3a and 3b) by cyclopropanation of double bond followed by nucleophilic substitution of F with different amines. The compounds were screened for their antitubercular and antimalarial activities against Mycobacterium tuberculosis H37Rv and Plasmodium falciparum 3D7 strains in vitro respectively. Several compounds (6a, 6d-6h, 6p, 6q and 8a-8c) exhibited good in vitro antitubercular activities with MIC values 3.12-12.5μg/mL and preferentially inhibited the growth of P. falciparum in vitro (4a, 4c, 6a-6d, 6f, 6s, 8a and 8c) with IC₅₀ as low as 0.080 and 0.035μg/mL and SI values 4975 and 6948, respectively. Molecular docking studies and in vitro evaluation against FAS-II enzymes using reporter gene assays were carried out to elucidate the mode of action of these molecules. Two compounds 4a and 6g showed significant inhibition at 25μM concentration of the compound.
一系列 4-烷基氨基芳基苯基环丙基甲酮（6a-6u 和 8a-8c）由 4-氟查耳酮（3a 和 3b）通过双键环丙烷化反应和不同胺的 F 亲核取代反应合成。这些化合物分别在体外筛选了对结核分枝杆菌 H37Rv 和恶性疟原虫 3D7 株的抗结核和抗疟活性。一些化合物（6a、6d-6h、6p、6q 和 8a-8c）表现出良好的体外抗结核活性，MIC 值为 3.12-12.5μg/mL，并且优先抑制恶性疟原虫在体外的生长（4a、4c、6a-6d、6f、6s、8a 和 8c），IC₅₀ 值低至 0.080 和 0.035μg/mL，SI 值分别为 4975 和 6948。进行了分子对接研究和使用报告基因测定法对 FAS-II 酶的体外评估，以阐明这些分子的作用模式。两种化合物 4a 和 6g 在 25μM 浓度的化合物下表现出显著的抑制作用。
