Design, synthesis, and evaluation of antitumor activity of five natural product conjugates

Quercetin, jatrorrhizine, berberine, dehydrocostus lactone, and magnolol are prominent compounds known for their antitumor properties. A series of chemical reactions such as protection, hydrolysis, Michael addition and substitution were conducted using rutin as the initial material to synthesize methyl-quercetin conjugates with berberine, jatrorrhizine, and dehydrocostus lactone. Additionally, jatrorrhizine and magnolol conjugates were synthesized through a two-step substitution process. The resulting products were structurally confirmed using 1 H-NMR, 13 C-NMR, ESI-MS and ESI-HRMS techniques. The MTT assay was employed to preliminarily assess the in vitro antiproliferative effects of these compounds on four tumor cell lines: MHCC97H, HCC827, Hela, and HEL. Results indicated that the final conjugated products generally showed more potent inhibitory effects on tumor cell proliferation than the original lead compounds. In particular, final product 7 exhibited an inhibitory effect on the MHCC97H tumor cell line that was comparable to a positive control drug, highlighting its potential as a candidate for antitumor drug development. Molecular docking studies were conducted on final product 7 to explore its affinity and binding interactions with VEGFR-2 and TrxR1 proteins, aiming to elucidate its binding characteristics and possible antitumor mechanisms.