Design, synthesis and cytotoxic activity of novel 1-aroyl-4-(2-chloroethyl)semicarbazides

Abstract

A series of aroyl derivatives of 4-(2-chloroethyl)semicarbazide were designed and synthesized to explore their antiproliferative activity against human brain carcinoma (U251) and human liver carcinoma (Hepg2) cell lines. The synthesized compounds were characterized by elemental analyses and spectroscopic data. It was established that compounds in which semicarbazide fragments are substituted with a (2-indolyl)carbonyl moiety showed a higher cytotoxic activity than the corresponding benzoyl derivatives. 1-[(5-Benzyloxy-1H-indol-2-yl)carbonyl]-4-(2-chloroethyl)semicarbazide (24) showed the highest cytotoxic activity against Hepg2 (IC 50 = 21 mg/ml), while 4-(2-chloroethyl)-1-[(5-methoxy-1H-indol-2-yl)carbonyl]semicarbazide (23) was the most active compound against U251 (IC 50 = 8 mg/ml).

Synthesis of Hydrazone Derivatives of 4-(2-Chloroethyl) semicarbazide : A New Class of Cytotoxic Agents

“…In our previous work, a series of benzamides (D) and 2-indolecarboamides (E) derivatives of the 4-(2-chloroethyl)semicarbazide were prepared 13 as a new class of cytotoxic agents. These derivatives were structurally related to 1-aryl-3-(2-chloroethyl) ureas derivatives with some structural variations whereas the aryl moiety whether p-substituted phenyl (D) or 5-substituted indolyl (E) was linked indirectly to (2-chloroethyl)urea function through carbonylamino moiety.…”

Synthesis and Biological Activity Research of 4-Substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) Semicarbazides

“…[7～12] Molecular hybridization is a new valuable structure modification method in drug design and development, based on the combination of pharmacophoric moieties of different bioactive substances to generate a new hybrid compound with improved efficacy, low toxicity and undesired side effects. [13,14] Bipyridine [6] and semicarbazides [15] have already been demonstrated antitumor activity, with the aim of developing antitumor candidates with improved properties, a series of 4-substitued-1-(2-methyl-6-(pyridin-3-yl)-nicotinoyl) semicarbazides 4a～4r (Figure 1) were designed and synthesized by the molecular hybridization strategy. The cytotoxicity in vitro against QGY7703, NCl-H460, and MCF7 cell lines was evaluated by the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay.…”

Anticancer Screening and Structure Activity Relationship Study of Some Semicarbazides and 1,2,4-Triazolin-5-ones

“…Semicarbazides, linear analogues, commonly applied in the 1,2,4-triazole synthesis, are also an important class of compounds of diverse biological properties [13,14]. Some of them exhibit a promising cytotoxic activity profile [15,16].…”