Synthesis and Biological Evaluation of a Series of 6,7-dimethoxy-1-(3,4- dimethoxybenzyl)-2-substituted Tetrahydroisoquinoline Derivatives

Abstract

Multidrug resistance in cancer is a major cause of failure in cancer chemotherapy. In search of new compounds with strong reversal activity and simple molecular structure, we have synthesized a series of compounds in which different substituents were linked to the 2-position of the 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)- tetrahydroisoquinoline system. Compounds were analyzed for their cytotoxicity by MTT in K562 cell line in vitro, all of the derivatives exhibited little cytotoxic activity. In the meantime, these compounds were evaluated by MTT in K562/A02 cell line in vitro, 6e, 6h and 7c exhibited similar or more potent activities than verapamil with the IC50 values at 0.66, 0.65 and 0.96μM, and with the ratio factor of 24.13, 24.50 and 16.59, respectively.

The Pictet-Spengler Reaction Updates Its Habits

“…Several substituted THIQ [27][28][29][30][31][32][33][34][35][36][37][38][39][40] and THBC have been designed, synthesized via P-S cyclization, and evaluated for their biological activities. The list comprehends aminopeptidase N (APN) inhibition [27], multidrug resistance reversal effect [28], cytotoxicity against K562 [29], nonsaccharide activators of antithrombin [31], anticoagulants [32], microtubule disruptors for antiproliferative activity [33,34], cytotoxicity against MOLT-3 [35] or HepG2 [36] cell lines, and the inhibitory activity towards cisplatin-insensitive cell line Skov3 [37] or the growth of Mycobacterium tuberculosis [39] for THIQ. For THBC, the inhibition of topoisomerase II [41], the oncogenic RASlethality [47], and the antimalarial activity of spirocyclic structures [44][45][46]56,60] were the most studied biological properties.…”