Synthesis, in-vitro cytotoxicity of 4H-benzo[h]chromene derivatives and structure–activity relationships of 4-aryl group and 3-, 7-positions

Abstract

A series of 2-amino-4

Design and Synthesis of Novel Heterocyclic-Based 4H-benzo[h]chromene Moieties: Targeting Antitumor Caspase 3/7 Activities and Cell Cycle Analysis

“…β -enaminonitrile is a versatile precursor to the manufacturing of several functionalized heterocycles with a remarkable biological performance [13,14,15,16,17,18,19,20,21,22]. Thus, the synthesis of chromene- and pyrimidine-containing compounds has drawn considerable notice, seen in Scheme 1, Scheme 2, Scheme 3 and Scheme 4.…”

“…This result could be attributed to the steric hindrance of the methoxy group at the 2-position of the 2,4-dimethoxybenzaldehyde. Compound 4 displayed optical activity of zero rotation (i.e., it was optically inactive) and, thus, was in the form of a racemic (±) mixture [17,26], as shown in Scheme 1.…”

“…The in vitro antiproliferative performance of compounds 4 , 7 – 11 , and 12 – 16 towards breast cancer MCF-7, human colon cancer HCT-116, and liver cancer HepG-2 cell lines was explored, as shown in Figure 4 and Table 1. The judicious choice of the cell lines and standard drugs was instigated by the asserted anticancer behavior of a number of benzochromene and chromenopyrimidine molecules [13,14,15,16,17,18,19,20,21,22,23,24,25,26]. Their cytotoxic activities were evaluated via the 2-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl-2 H -tetrazol-3-ium bromide (MTT) colorimetric assay [28,29], and the obtained IC 50 values were in comparison to the values of the reference cytotoxic drugs: Doxorubicin, Vinblastine, and Colchicine.…”

“…The 2- N -succinimido derivatives ( B ) display an anti-rheumatic effect [15], while β -enaminonitriles ( C ) [16] have effective cytotoxic and apoptotic behaviors against different cell lines: MCF-7, MDA-MB-231, HepG-2, T-47D, SK-N-MC, KB, and PC3. Furthermore, β -enaminonitriles/esters (D) [17,18,19,20,21,22] are reported to be one of the most antiproliferative agents, shown in Figure 1.…”

“…These findings encouraged us to develop a novel series of chromene and pyrimidine molecules with the aim of discovering their antitumor features [17,18,19,20,21,22,26]. The SAR of the desired molecules stressed the influence of the substituents at different positions on the antitumor activity.…”