Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Parasitology Division, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Bioorg Chem. 2018 Oct;80:204-211. doi: 10.1016/j.bioorg.2018.06.012. Epub 2018 Jun 5.
A series of short chain 4-aminoquinoline-imidazole derivatives have been synthesized in one pot two step multicomponent reaction using van leusen standard protocol. The diethylamine function of chloroquine is replaced by substituted imidazole derivatives containing tertiary terminal nitrogen. All the synthesized compounds were screened against the chloroquine sensitive (3D7) and chloroquine resistant (K1) strains of Plasmodium falciparum. Some of the compounds (6, 8, 9 and 17) in the series exhibited comparable activity to CQ against K1 strain of P. falciparum. All the compounds displayed resistance factor between 0.09 and 4.57 as against 51 for CQ. Further, these analogues were found to form a strong complex with hematin and inhibit the β-hematin formation, therefore these compounds act via heme polymerization target.
已经使用范吕森标准方案通过一锅两步多组分反应合成了一系列短链 4-氨基喹啉-咪唑衍生物。氯喹的二乙胺官能团被含有叔端氮的取代咪唑衍生物取代。所有合成的化合物都针对氯喹敏感（3D7）和氯喹抗性（K1）的恶性疟原虫株进行了筛选。该系列中的一些化合物（6、8、9 和 17）对恶性疟原虫 K1 株的活性与 CQ 相当。所有化合物的耐药因子在 0.09 到 4.57 之间，而 CQ 的耐药因子为 51。此外，这些类似物被发现与血红素形成强复合物并抑制β-血红素形成，因此这些化合物通过血红素聚合靶标起作用。
