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., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna 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 Triticum aestivum L., while on Artemia franciscana Kellogg nauplii, only compounds 2c and 4c had moderate toxicity. On Daphnia magna, 4b and 4c showed high toxicity; 2a, 2b, and 2c moderate to high toxicity; only 4a and 4d 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 4a and its homologue 4d, especially against LoVo colon cells.

Synthesis, Characterization and Cytotoxic Evaluation of New Pyrrolo[1,2-b]pyridazines Obtained via Mesoionic Oxazolo-Pyridazinones

“…The high sensibility of Daphnia magna versus Artemia sp. was also observed in our previous studies on compounds with pyrrole structure [49].…”

“…The potential anti-proliferative effects of treatments with the new compounds under study were evaluated in vitro against solid tumor-derived cells of different histological origin vs. normal human endothelial cells. Therefore, several compound-mediated cytotoxicity assays were performed using three adherent tumor standardized cell lines derived from human colon adenocarcinoma LoVo [50][51][52][53], breast adenocarcinoma MCF-7 [49,54], and ovary adenocarcinoma SK-OV-3 [49,55], and compared to normal human umbilical vein endothelial cells (HUVEC) [56]. The cytotoxic activity of the newly synthesized compounds was compared to the one induced by cisplatin (Cis-Pt), 5-fluorouracil (5-FU), or doxorubicin (DOX), commonly used drugs for oncological treatments of cancers, and applied as positive controls throughout our experiments.…”

Untitled

“…From the results it was predicted that the unsubstituted phenyl ring at 4, 5 position reduces the excessive sugar level similarly the substitution of phenyl ring at 3,4 position resulted the complete reduction of antihyperglycemic activity. The substitution of trifluoromethyl group at the 3 position of the aryl group hence it possessed the good antidiabetic activity 20,21,23,24 .…”

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

“…Briefly, 1.5 x 10 4 cells/well were cultured in 100 µL of the medium; after 24h, culture supernatants were discarded, and the cells were treated with increasing concentrations of BVE, BS, or reference drug solutions for 24 h or 48 h. At the expiration of the contact time, 20 µL of reagent mixture was added to each well, and the culture dishes were incubated for an additional 4 h at 37 •C, with gentle shaking every 20 min. Absorbance was read at λ = 492 nm with the Dynex ELISA reader (DYNEX Technologies-MRS, USA) [42].…”