Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents
AbstractA selected set of substituted pyridone-annelated isoindigos 3a–f has been synthesized via interaction of 5- and 6-substituted oxindoles 2a–f with 6-ethyl-1,2,9-trioxopyrrolo[3,2-f]quinoline-8-carboxylic acid (1) in acetic acid at reflux. Among these isoindigos, the 5'-chloro and 5'-bromo derivatives 3b and 3d show strong and selective antiproliferative activities against a panel of human hematological and solid tumor cell-lines, but not against noncancerous cells, suggesting their potential use as anticancer agents. In all the tested cell lines, compound 3b was a 25%–50% more potent inhibitor of cell growth than 3d, suggesting the critical role of the substitution at 5'-position of the benzo-ring E. The IC50 values after 48 hours incubation with the 5'-chloro compound 3b were 6.60 µM in K562, 8.21 µM in THP-1, 8.97 µM in HepG2, 11.94 µM in MCF-7 and 14.59 µM in Caco-2 cancer cells, while the IC50 values in noncancerous HEK-293 and L-929 were 30.65 µM and 40.40 µM, respectively. In addition, compound 3b induced higher levels apoptosis in K562 cells than 3d, as determined by annexin V/7-AAD flowcytometry analysis. Therefore, further characterization of the antitproliferative mechanisms of compounds 3b and 3d may provide a novel chemotherapeutic agents. View Full-Text
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Saleh, A.M.; Al-As'ad, R.M.; El-Abadelah, M.M.; Sabri, S.S.; Zahra, J.A.; Alaskar, A.S.; Aljada, A. Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents. Molecules 2014, 19, 13076-13092.
Saleh AM, Al-As'ad RM, El-Abadelah MM, Sabri SS, Zahra JA, Alaskar AS, Aljada A. Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents. Molecules. 2014; 19(9):13076-13092.Chicago/Turabian Style
Saleh, Ayman M.; Al-As'ad, Randa M.; El-Abadelah, Mustafa M.; Sabri, Salim S.; Zahra, Jalal A.; Alaskar, Ahmed S.; Aljada, Ahmad. 2014. "Synthesis and Biological Evaluation of New Pyridone-Annelated Isoindigos as Anti-Proliferative Agents." Molecules 19, no. 9: 13076-13092.