Design, Synthesis, and Screening of 5-Aryl-3-(2-(pyrrolyl)thiophenyl)-1,2,4-oxadiazoles as Potential Antitumor Molecules on Breast Cancer MCF-7 Cell Line

Abstract

The work reported the design and cytotoxic screening of synthetic small molecules: carbonitriles 3a-c, carboximidamides 4a-c, and oxadiazoles 5-19 as antitumor molecules. Molecules 4c, 9, 12, and 14 show promising cytotoxicity profiles against two cell lines higher than prodigiosin (PG). The results of topoisomerase enzyme inhibition assay show that carboximidamide 4c and oxadiazole 14 display potent inhibitory activity in nano-molar concentration higher than PG. In addition, carboximidamide 4c and oxadiazoles 9, 12, and 14 exhibit antiproliferative activities over MCF-7 cells by cell cycle arrest at G 1 phase and apoptosis inducing activity by increasing cell population percentages at pre G 1 and G 2 /M phases as shown by DNA-flow cytometry assay and annexin V analysis. Moreover, measurement of p53 and cell death mediators, show that carboximidamide 4c and oxadiazoles 9, 12, and 14 significantly up-regulate p53, Puma and Bax/Bcl-2 ratio levels. Subsequently, pro-apoptotic activities are confirmed by active caspase 3/7 percentages green fluorescence assay.

Transporter-Targeted Bile Acid-Camptothecin Conjugate for Improved Oral Absorption

“…3D Multicellular Tumor Spheroids Culture The Caco-2 spheroids were cultured by using the liquid overlay method as described previously. 25) After reaching 90% confluence, cells were digested by trypsin and collected. Next, the cell number was counted using a hemocytomete and the cell concentration was diluted to a density of 1 × 10 4 cells/mL using growth medium.…”

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

“…Conjugation of 1,2,4-oxadiazoles to thiophene, performed by Mohammed et al, led to significant toxicity on MCF-7 and HTC-116, with the identification of potent antiproliferative agent 39 ( Figure 7 ) [ 59 ], characterized by IC 50 value of 0.19 ± 0.05 µM on MCF-7 cells. This compound strongly inhibited topo II and, as confirmed by flow cytometry analysis, induced cell cycle arrest at G1 phase.…”

“…This compound strongly inhibited topo II and, as confirmed by flow cytometry analysis, induced cell cycle arrest at G1 phase. Its proapoptotic behavior was further demonstrated by increased levels of p53 protein and other cell death modulators (Puma, Bax, and Bcl-2), measured through Western blot analysis [ 59 ].…”

Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

“…Conjugation of 1,2,4-oxadiazoles to thiophene, performed by Mohammed et al, led to significant toxicity on MCF-7 and HTC-116, with the identification of potent antiproliferative agent 39 (Figure 7) [59], characterized by IC50 value of 0.19 ± 0.05 µM on MCF-7 cells. This compound strongly inhibited topo II and, as confirmed by flow cytometry analysis, induced cell cycle arrest at G1 phase.…”

“…This compound strongly inhibited topo II and, as confirmed by flow cytometry analysis, induced cell cycle arrest at G1 phase. Its pro-apoptotic behavior was further demonstrated by increased levels of p53 protein and other cell death modulators (Puma, Bax and Bcl-2), measured through Western-Blot analysis [59].…”