Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents

Abstract

Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM, respectively. Regarding the protein kinase inhibition assay, 3c inhibited seven different kinases and 4a strongly inhibited the CK1δ/ε kinase. The studied kinases are involved in several cellular functions such as proliferation, migration, cell death and cell cycle progression. Additional analysis by flow cytometry revealed that 3c and 4a caused depolarization of the mitochondrial membrane, suggesting apoptosis mediated by the intrinsic pathway. Compound 3c induced arrest in G1 phase of the cell cycle on HL-60 cells, and in the annexin V assay approximately 50% of cells were in apoptosis at the highest concentration tested (26 μM). Compound 4a inhibited cell cycle by accumulation of abnormal postmitotic cells at G1 phase and induced DNA fragmentation at the highest concentration (22 μM).

Electrochemical oxo-functionalization of cyclic alkanes and alkenes using nitrate and oxygen

“…Derivatization of the aldehydes to semicarbazones 13 was carried out on the one hand, to prevent further autooxidation of the aldehyde and therefore falsification of the yield determination, and on the other hand to provide a simple protocol for semicarbazone 13 synthesis. Semicarbazones show pharmacological versatility and are known for their anticonvulsant 66 , 67 and potential anticancer 68 properties.

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Apoptosis in megakaryocytes: Safeguard and threat for thrombopoiesis

“…When cells are exposed to various stimulating factors, such as hypoxia, oncogene activation, DNA damage, and lack of cytotropic factors, homeostasis of the mitochondrial membrane is destroyed, and the permeability of the mitochondrial membrane increases. The pro-apoptotic factors in the mitochondrial membrane are released into the cytoplasm, activating the intrinsic apoptotic pathway, and ultimately causing cell death ( 66 ).…”