No abstract

Carbazole alkaloids, as an important class of natural products, have been widely reported to have extensive biological activities. Based on our previous three-component reaction to construct carbazole scaffolds, we introduced a methylene group to provide a rotatable bond, and designed series of carbazole derivatives with structural diversity including carbazole amide, carbazole hydrazide and carbazole hydrazone. All synthesized carbazole derivatives were evaluated for their in vitro cytotoxic activity against 7901 (gastric adenocarcinoma), A875 (human melanoma) and MARC145 (African green monkey kidney) cell lines. The preliminary results indicated that compound 14a exhibited high inhibitory activities on 7901 and A875 cancer cells with the lowest IC50 of 11.8 ± 1.26 and 9.77 ± 8.32 μM, respectively, which might be the new lead compound for discovery of novel carbazole-type anticancer agents.

As an important class of natural products, pyrazole alkaloids have a large number of applications in various aspects such as medicines and pesticides. Due to the special position of its amino group, 3-aminopyrazole is easy to form a hydrogen bond donor-acceptor-donor, and the hydrogen bond “zipper” structure enhances the binding ability of such compounds to receptors. This work provides a new one-pot three-components reaction for the efficient construction of multi-substituted aminopyrazoles derivatives via iodine-mediated cyclization in the presence of ethanol. After that, the potential mechanism of the reaction was explored based on the control transformation experimental and density functional theory (DFT) calculations. In addition, all obtained multi-substituted aminopyrazole derivatives were fully investigated for their application as potential anti-cancer agents, and some of which have been proved to exhibit excellent anti-cancer activity against A875, HepG2, and HL-7702 cell lines, and the possible structure-activity relationships also has been discussed based on the screening results. The kinase assay and molecular docking experimental indicate that this class of compounds may be a potential CDK1 inhibitors.