Design, synthesis and antiproliferative activity of urocanic-chalcone hybrid derivatives

Abstract

Inspired by biologically active natural products, a hybrid analogue that combines the N-Me urocanic side chain of the sarcodictyin family of compounds with the chalcone motif has been proposed, synthesised and examined for antiproliferative activity in three cancer cell lines and one normal primary cell line. The analogues are all synthesised in one or two steps from commercially available materials and, of the compounds examined, the proposed hybrid analogue displays the most active and selective inhibition of cell proliferation in human colon cancer cell line HT29 (IC 50 2.9 µM) and highly metastatic human breast carcinoma MDA-MB-231 (IC 50 4.8 µM).

Synthesis and antiproliferative activity of some 3-(pyrid-2-yl)-pyrazolines

“…26 The effect of an N-benzoyl substituent (8h) was also investigated and exhibited no observable antiproliferative activity in the two cell lines examined (entry 8, Table 1). Following our previous studies using 3,4,5-trimethoxyphenyl substituents, 31 which have been shown to play crucial roles in activity, [32][33][34][35][36] we investigated this substitution pattern in the N-benzoyl group. Remarkably, the corresponding 3,4,5-trimethoxybenzoyl derivative 8i displayed potent activity and selectivity for the highly metastatic human breast carcinoma (MDA-MB-231, entry 9).…”

A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry

“…Further, tubulin-targeting compounds including taxanes, vinca alkaloids, and combretastatins have been widely used in the treatment of many cancers [111,112]. The poor bioavailability and multidrug resistance of these drugs compel researchers to exploit novel inhibitors toward microtubule polymerization with low side effect, little drug resistance, and good oral activity [113,114].…”

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

“…Therefore, the discovery of potential microtubule inhibitors is an attractive strategy for cancer therapy. Although tubulin‐targeting compounds including taxanes, vinca alkaloids, and combretastatins have been widely used in the treatment of many cancers, the poor bioavailability and multidrug resistance of these drugs compel researchers to exploit novel inhibitors toward microtubule polymerization with low side effect, little drug resistance, and good oral activity . The structures for imidazoles as microtubule polymerization inhibitors are shown in Figure .…”