New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

Abstract

The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, ¹H-NMR and ¹³C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., <i>Triticum aestivum</i> L.) and animal cells using aquatic crustaceans (i.e., <i>Artemia franciscana</i> Kellogg and <i>Daphnia magna</i> Straus). The potential antitumor activity of several of the pyrrole derivatives was studied by performing in vitro cytotoxicity assays on human adenocarcinoma-derived cell lines (i.e., LoVo (colon), MCF-7 (breast), and SK-OV-3 (ovary)) and normal human umbilical vein endothelial cells (HUVECs). The obtained results of the cytotoxicity assessment indicated that the tested compounds had nontoxic activity on <i>Triticum aestivum</i> L., while on <i>Artemia franciscana</i> Kellogg nauplii, only compounds <b>2c</b> and <b>4c</b> had moderate toxicity. On <i>Daphnia magna</i>, <b>4b</b> and <b>4c</b> showed high toxicity; <b>2a</b>, <b>2b</b>, and <b>2c</b> moderate to high toxicity; only <b>4a</b> and <b>4d</b> were nontoxic. The compound-mediated cytotoxicity assays showed that several pyrrole compounds demonstrated dose- and time-dependent cytotoxic activity against all tested tumor cell lines, the highest antitumor properties being achieved by <b>4a</b> and its homologue <b>4d</b>, especially against LoVo colon cells.